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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation K65R

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 53 clinical trials

Clinical Trials


1 See Detailed Description

This study was designed to test the efficacy, safety, tolerability and durability of the antiviral response between atazanavir (ATV) + ritonavir (/r) + abacavir/lamivudine(ABC/3TC) Fixed dose combination (FDC) each administered once daily (QD) for 36 weeks followed by randomization to either a simplification regimen of ATV or continuation of ATV +/r for an additional 48 weeks, each in combination with ABC/3TC in antiretroviral (ART)-naive, HIV-1 infected, HLA-B*5701 negative subjects. All subjects who complete the 84-week study will be eligible to enter the treatment extension phase and continue for an additional 60 weeks. The purpose of this extension is to obtain longer term treatment data in subjects who have completed the 84-week study.

NCT00440947
Conditions
  1. Infection, Human Immunodeficiency Virus I
  2. HIV Infection
Interventions
  1. Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r)
  2. Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV)
MeSH:Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome

- Subject testing positive for Hepatitis B or both Hepatitis B and Hepatitis C at screening (+ HbsAg) - Genotyping results performed at the screening indicate that the subject has any of the following mutations at the reverse transcriptase (RT) enzyme: K65R, L74V, or Y115F, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, or ≥ 3 of the following protease mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50, I54, A71, G73, V77, V82, I84, N88, and L90. - Women who are pregnant or breastfeeding. --- K65R ---

Primary Outcomes

Description: The percentage of PAR with HIV-1 RNA virus <50 c/ml determined from a blood sample drawn at Week 84 was tabulated by treatment arm with stratification by baseline HIV-1 RNA (<100,000 c/ml and >=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed viral load <50 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <50 c/ml, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 50 c/ml, or had an unconfirmed HIV RNA of at least 50 c/ml at last visit.

Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c) /Milliliter (ml) at the Week 84 Visit

Time: Week 84

Secondary Outcomes

Description: The mean age of participants randomized to treatment in the Randomized Phase was calculated at Baseline.

Measure: Mean Age at Baseline of Participants Randomized to Treatment for the 48-Week Randomized Phase

Time: Baseline of Randomized Phase

Description: The percentage of PAR with HIV-1 RNA virus <50 c/ml from a Week 36 blood sample was tabulated. Per TLOVR algorithm, responders were PAR with confirmed viral load <50 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <50 c/ml, prematurely discontinued (DC) study or study medication (any reason), had confirmed rebound to >=50 c/ml, or had an unconfirmed HIV RNA >=50 c/ml at last visit. ITT-E observed analysis (Obs): all observed data. ITT-E M/D=F analysis: PAR with missing data/data collected after study medication DC were failures.

Measure: Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 36 Visit

Time: Week 36

Description: A blood sample was drawn to determine the amount of HIV-1 RNA virus in c/ml at Week 84. The percentage of participants with HIV-1 RNA <50 c/ml at Week 84 was tabulated. The secondary analysis methods were: Observed (Obs; uses all visits with data in the analysis period), and missing/discontinuation=failure (M/D=F) analyses. M/D=F: participants with missing data or data collected after study medication DC were considered failures.

Measure: Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 84 Visit

Time: Week 84

Description: Percentage of PAR with HIV-1 RNA <50 c/ml at Week 144 was tabulated; stratified by baseline HIV-1 RNA (<100,000 and >=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV RNA <50 c/ml who had not met any non-responder (NR) criterion. NR were PAR who never achieved CF HIV RNA <50 c/ml, prematurely discontinued (DC) study or study medication (Med), had CF rebound to >=50 c/ml, or had an unconfirmed HIV RNA >=50 c/ml at last visit. Observed analysis (Obs): all observed data. M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.

Measure: Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 144 Visit

Time: Week 144

Description: The percentage of PAR with HIV-1 RNA virus <400 c/ml from a Week 36 blood sample was tabulated. Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV RNA <400 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved CF HIV RNA <400 c/ml, prematurely discontinued (DC) study or study medication (Med; any reason), had CF rebound to >=400 c/ml, or had an unconfirmed HIV RNA >=400 c/ml at last visit. ITT-E observed analysis (Obs): all observed data. ITT-E M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.

Measure: Percentage of Participants Who Achieved Plasma HIV-1 RNA <400 c/ml at the Week 36 Visit

Time: Week 36

Description: Percentage of PAR with HIV-1 RNA <400 c/ml at Week 84 was tabulated; stratified by baseline HIV-1 RNA (<100,000 and >=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV-RNA <400 c/ml who had not met any non-responder (NR) criterion. NR were PAR who never achieved CF HIV RNA <400 c/ml, prematurely discontinued (DC) study or study medication (Med), had CF rebound to >=400 c/ml, or had an unconfirmed HIV RNA >=400 c/ml at last visit. Observed analysis (Obs): all observed data. M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.

Measure: Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 84 Visit

Time: Week 84

Description: Percentage of PAR with HIV-1 RNA <400 c/ml at Week 144 was tabulated; stratified by baseline HIV-1 RNA (<100,000 and >=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV-RNA <400 c/ml who had not met any non-responder (NR) criterion. NR were PAR who never achieved CF HIV RNA <400 c/ml, prematurely discontinued (DC) study or study medication (Med), had CF rebound to >=400 c/ml, or had an unconfirmed HIV RNA >=400 c/ml at last visit. Observed analysis (Obs): all observed data. M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.

Measure: Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 144 Visit

Time: Week 144

Description: The number of participants that failed to respond to therapy through 36 weeks on treatment, based on the protocol definition of virologic failure (PDVF), was tabulated. PDVF was defined as (a) failure to achieve plasma HIV-1 RNA <400 c/ml by Week 30 or (b) confirmed HIV-1 RNA rebound >=400 c/ml after achieving HIV-1 <400 c/ml.

Measure: Number of Participants Who Met the Protocol-defined Virologic Failure (PDVF) Criteria at Week 36

Time: Week 36

Description: The number of participants that failed to respond to therapy from the time of treatment randomization through Week 84, based on the protocol definition of virologic failure (PDVF), was tabulated. PDVF was defined as (a) failure to achieve plasma HIV-1 RNA <400 c/ml by Week 30 or (b) confirmed HIV-1 RNA rebound >=400 c/ml after achieving HIV-1 <400 c/ml.

Measure: Number of Participants Who Met the PDVF Criteria at Week 84

Time: Week 84

Description: The number of participants enrolled in the extension phase that failed to respond to therapy from Week 84 through Week 144, based on the protocol definition of virologic failure (PDVF) was tabulated,. PDVF was defined as (a) failure to achieve plasma HIV-1 RNA <400 c/ml by Week 30 or (b) confirmed HIV-1 RNA rebound >=400 c/ml after achieving HIV-1 <400 c/ml.

Measure: Number of Participants Who Met the PDVF Criteria at Week 144

Time: Week 144

Description: Change from baseline was calculated as the Week 36 value minus the baseline value. Blood was drawn to analyze for plasma HIV viral load.

Measure: Change From Baseline in HIV-1 RNA at Week 36

Time: Baseline and Week 36

Description: Change from baseline was calculated as the Week 84 value minus the baseline value. Blood was drawn to analyze for plasma HIV viral load.

Measure: Change From Baseline in HIV-1 RNA at Week 84

Time: Baseline and Week 84

Description: Change from baseline was calculated as the Week 144 value minus the baseline value. Blood was drawn to analyze for plasma HIV viral load.

Measure: Change From Baseline in HIV-1 RNA at Week 144

Time: Baseline and Week 144

Description: Blood was drawn to analyze for CD4+ cell count. A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from baseline was calculated as the Week 36 value minus the baseline value.

Measure: Change From Baseline in CD4+ Cell Count at Week 36

Time: Baseline and Week 36

Description: A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from baseline was calculated as the Week 84 value minus the baseline value. Blood was drawn to analyze for CD4+ cell count.

Measure: Change From Baseline in CD4+ Cell Count at Week 84

Time: Baseline and Week 84

Description: A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from baseline was calculated as the Week 144 value minus the baseline value. Blood was drawn to analyze for CD4+ cell count.

Measure: Change From Baseline in CD4+ Cell Count at Week 144

Time: Baseline and Week 144

Description: A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New resistance-associated mutations (defined by the International AIDS Society-USA guidelines) that developed at the time of failure were tabulated by drug class. PAR, participants; VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Measure: Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 36

Time: Baseline through Week 36

Description: A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDs Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Measure: Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Randomization at Week 36 Through Week 84

Time: Randomization at Week 36 through Week 84

Description: A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDs Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Measure: Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Week 84 Through Week 144

Time: Week 84 through Week 144

Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at baseline. PAR, participant.

Measure: Number of Confirmed Virologic Failure Participants From Baseline Through Week 36 With Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir

Time: Baseline through Week 36

Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at baseline. PAR, participant.

Measure: Number of Confirmed Virologic Failure Participants From Randomization at Week 36 Through Week 84 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir

Time: Randomization at Week 36 through Week 84

Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at baseline. PAR, participant.

Measure: Number of Confirmed Virologic Failure Participants From Week 84 Through Week 144 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir

Time: Week 84 through Week 144

Description: Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.

Measure: Mean Percent Compliance at Week 36

Time: Week 36

Description: Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.

Measure: Mean Percent Compliance at Week 84

Time: Week 84

Description: Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.

Measure: Mean Percent Compliance at Week 144

Time: Week 144

2 Phase 2 Dose-escalating, P-C, D-B, Parallel Group Study in HIV Treatment-experienced Patients to Evaluate the Safety, Tolerability and Efficacy of PA103001-04 Administered as Functional Monotherapy for 14 Days *(PART B)

The purpose of this study is to evaluate antiretroviral activity of up to five different oral doses administered for two weeks of bevirimat versus placebo in HIV treatment experienced patients, who have documented genotypic resistance to at least one major mutation from the IAS-USA list (2007)of resistance mutations for NRTIs, NNRTIs, or PIs. Patients will also be monitored for side effects, and the pharmacokinetics of bevirimat will be determined.

NCT00511368
Conditions
  1. HIV Infections
Interventions
  1. Drug: matching placebo
  2. Drug: Bevirimat
MeSH:HIV Infections

- Have documented evidence of genotypic resistance in their medical records (at screening) or have resistance at screening by genotype to any major mutation from the IAS-USA list of resistance drug mutations, defined as: NRTI resistance: M41L, K65R, D67N, K70R, K70E, L74V, Y115F, M184V, M184V/I, L210W, T215Y/F, K219Q/E; NNRTI resistance: L100I, K103N, V106M, V106A/M, V108I, Y181C, Y181C/I, Y188L, Y188C/L/H, G190S/A, G190A, P225H; Major PI resistance: D30N, V32I, L33F, M46I/L, I47V/A, G48V, I50L, I50V, I54M/L, L76V, V82A/F/T, V82A/F/T/S, V82L/T, I84V, N88S, L90M - Be receiving an antiretroviral therapy regimen containing at least 3 drugs (regimens containing ritonavir must not exceed a total daily dose of 400 mg) which has been unchanged for at least 8 weeks prior to initial screening. --- M41L --- --- K65R ---

Primary Outcomes

Measure: HIV-1 RNA change from baseline over the first 14 days of study

Time: 14 days

Secondary Outcomes

Measure: safety and tolerability; pharmacokinetics

Time: 14 days

3 Once-daily Antiretroviral Therapy in HIV-1 Infected Patients With CD4+ Cell Counts Below 100 Cells/Mcl. A Prospective, Randomized, Multicentre, Open Clinical Study.

There are few randomized clinical trials in advanced HIV patients. This is a multicenter, randomized, open clinical trial, comparing three parallel groups, to compare the immunological reconstitution and the virological efficacy and safety of three different combinations of antiretroviral therapy given once a day (QD): tenofovir plus emtricitabine plus either efavirenz, lopinavir-ritonavir or atazanavir-ritonavir during 96 weeks in advanced antiretroviral naïve HIV-1 infected patients with less than 100 CD4+ T-cells/mm3. Primary endpoint is the median increase in CD4+ T-cell count at 48 weeks after starting HAART.

NCT00532168
Conditions
  1. HIV Infections
Interventions
  1. Drug: tenofovir + emtricitabine + efavirenz
  2. Drug: tenofovir + emtricitabine + lopinavir-ritonavir
  3. Drug: tenofovir + emtricitabine + atazanavir-ritonavir
MeSH:HIV Infections

- No mutations of drug resistance at baseline (M184V/I, K65R, resistance to efavirenz or 2 or more PRAMs (L33I/F/V, V82A/F/L/T, I84V, L90M) - Written informed consent Exclusion Criteria: - Hypersensibility to study drugs. --- M184V --- --- K65R ---

Primary Outcomes

Measure: Median increase in CD4+ T-cell count at 48 weeks after starting the HAART combination randomly assigned

Time: 48 weeks

4 A Phase II, Randomized Trial of Open-Label Truvada With Darunavir/Ritonavir Versus Multiclass Therapy With Truvada, Darunavir/Ritonavir, Maraviroc and Raltegravir in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects

The researchers are involved in a phase II, randomized, two-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced darunavir with Truvada to a 5-drug multi-class regimen including truvada, darunavir/ritonavir/maraviroc/and raltegravir on acutely HIV-1-infected, antiretroviral (ARV) drug-naïve men and women. Subjects will participate for at least 60 weeks and up to 96 weeks if in the opinion of the investigator and patient that continued therapy is in the patient's best interest. Hypotheses: - Multi-class antiretroviral therapy (ART) is superior to RTV-enhanced ATV in combination with Emtricitabine/Tenofovir DF (FTC/TDF) with respect to suppression of viral replication. - Multi-class ART is superior to RTV-enhanced ATV in combination with FTC/TDF with respect to immune reconstitution in peripheral blood and in the gastrointestinal mucosa. - Multi-class ART is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to tolerability.

NCT00525733
Conditions
  1. HIV Infections
Interventions
  1. Drug: darunavir 800 mg
  2. Drug: FTC 200 mg/TDF 300mg
  3. Drug: Maraviroc
  4. Drug: Raltegravir
  5. Drug: Ritonavir 100 mg
MeSH:Infection HIV Infections

Major resistance-associated mutations include: NRTI: K65R or inserts Q151M, M184V/I, PI: I50L/V, I84V, N88S. --- K65R ---

Primary Outcomes

Measure: The Primary Outcome of This Study is the Proportion of Patients Having Detectable HIV-1 RNA Using the Single Copy Assay After 48 Weeks of Treatment and the Study Hypothesis is That New Treatment is Better Than the Control Group.

Time: 48 weeks

5 ADORE: A Single-arm, Phase 3, Pilot Study Investigating the Efficacy of Doravirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With Non-nucleoside Reverse Transcriptase Inhibitor Resistance

This is a pilot study investigating the efficacy of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in adults living with HIV-1 experiencing virological failure on first-line Efavirenz-based antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor resistance

NCT04429152
Conditions
  1. HIV-1-infection
Interventions
  1. Drug: Doravirine/Lamivudine/Tenofovir

Exclusion Criteria: - Resistance to TDF on genotype (K65R) - "Significant resistance" to doravirine, denoted by a Stanford Score ≥ 15 on genotype - Virologic failure on any other regimen - Women who are pregnant at the time of the screening or enrolment visits - Active tuberculosis and/or are on anti-tuberculous therapy at the time of the screening or enrolment visits - Taking and cannot discontinue prohibited concomitant medications listed in protocol at least two weeks prior to the enrolment visit and for the duration of the study period. --- K65R ---

Primary Outcomes

Description: The proportion of participants with undetectable plasma HIV-1 RNA levels at Week 24 will be recorded.

Measure: Proportion of participants with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at week 24

Time: 24 weeks

Secondary Outcomes

Description: Evaluation of viral suppression by recording the proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48

Measure: Proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48

Time: At week 4, 12, 48

Description: Evaluation of changes in CD4 count from baseline recorded at weeks 24 and 48.

Measure: Change from baseline in plasma CD4 levels at weeks 24 and 48

Time: At week 24, 48

Description: Evaluation of the number of antiretroviral resistance mutations that emerge in participants with virological failure

Measure: Emergence of antiretroviral resistance mutations in participants with virological failure

Time: 48 weeks

6 Antiretroviral Activity and Tolerability of Once Daily Etravirine in Treatment-Naïve Adults With HIV-1 Infection

The main study is a single arm, open-label, prospective study to assess antiretroviral activity and tolerability of etravirine (TMC-125) 400 mg once daily, given with fixed-dose tenofovir/emtricitabine, in treatment-naïve HIV-1-infected men and women. There are also a genital secretions pharmacokinetic (PK) sub-study and a metabolic sub-study. The purpose of the genital secretions PK sub-study is to gain information about drug levels and HIV-1 RNA in genital secretions when subjects are taking etravirine. The purpose of the metabolic sub-study is to learn about the effects of etravirine on body composition, as well as lipid and glucose levels.

NCT00959894
Conditions
  1. HIV Infections
Interventions
  1. Drug: Etravirine (Intelence)
  2. Drug: Truvada
MeSH:Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome

2. Any of the following NRTI mutations: M184V/I, K70E/R, K65R, M41L, 69 insert, L210W, T215Y/F, K219Q/E, L74V. --- M184V --- --- K70E --- --- K65R ---

Primary Outcomes

Description: The primary study endpoint was the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 24 of study participation. The per-protocol primary analysis was conducted intention-to-treat, with missing evaluations counted as failures. Achievement of HIV-1 viral load below 50 copies/ml was defined as having HIV-1 RNA <50 copies/ml during the Week 24 analysis window (>18 and <30 weeks post-entry).

Measure: The Antiretroviral Activity of Etravirine 400 mg Given Once Daily, With Fixed-dose Truvada Once Daily, Among Treatment-naïve HIV-1 Infected Adults as Measured by the Percentage of Participants With HIV RNA < 50 Copies/mL at Week 24

Time: 24 weeks

Secondary Outcomes

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 48 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <50 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 48 weeks

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 96 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <50 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 96 weeks

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <200 copies/ml at Week 24 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <200 Copies/mL at Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 24 weeks

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <200 copies/ml at Week 48 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <200 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 48 weeks

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA 200 copies/ml at Week 96 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <200 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 96 weeks

Description: The per-protocol analysis of change in CD4+ cell count from baseline to Week 24 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% confidence interval (CI).

Measure: Change in CD4+ Cell Count From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: The per-protocol intention-to-treat analysis of change in CD4+ cell count from baseline to Week 48 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% CI.

Measure: Change in CD4+ Cell Count From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 48 weeks

Description: The per-protocol intention-to-treat analysis of change in CD4+ cell count from baseline to Week 96 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% CI.

Measure: Change in CD4+ Cell Count From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Per-protocol, genotype testing was conducted at confirmation of virologic failure if the confirmatory HIV-1 RNA was above the laboratory-specified threshold of 500 copies/mL. HIV-1 genotype was determined using the TRUGENE® HIV-1 assay (Siemens Healthcare Diagnostics, Tarrytown, NY)

Measure: Resistance Mutations in the Subset of Patients With Confirmed Virologic Failure Who Have HIV RNA >500 Copies/mL and Genotype Resistance Results

Time: 96 weeks

Description: The safety/tolerability endpoint was defined as the first grade 3 or higher sign, symptom or laboratory abnormality that was at least one grade higher than baseline among participants ever exposed to etravirine (regardless of treatment status), or permanent discontinuation of etravirine due to any toxicity (regardless of grade). Modification of tenofovir/emtricitabine was not a safety/tolerability event. The Kaplan-Meier method was used to estimate the proportion of participants ever exposed to etravirine who remained event-free through Week 96, with a 95% CI using Greenwood's variance estimate and a log-log transformation. Time was handled as continuous (weeks from treatment start to event or censoring).

Measure: Tolerability of Etravirine in HIV-1 Infected Adults Initiating Antiretroviral Therapy

Time: 96 weeks

Description: The Kaplan-Meier method was used to estimate the proportion of participants ever exposed to etravirine who remained event-free through Week 96, with a 95% CI using Greenwood's variance estimate and a log-log transformation. Time was handled as continuous (weeks from treatment start to event or censoring).

Measure: Probability of Remaining Free of a Safety/Tolerability Event at 96 Weeks

Time: 96 weeks

Description: Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 48 weeks

Description: Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 48 weeks

Description: Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5.

Measure: Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Changes from baseline to follow-up in limb fat, trunk fat, total body fat, and lean mass were calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Limb and Trunk Fat Distribution as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: Changes from baseline to follow-up in limb fat, trunk fat, total body fat, and lean mass were calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Limb and Trunk Fat Distribution as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Change from baseline to follow-up in fat mass ratio was calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Fat mass ratio was calculated as the ratio of trunk fat percentage and lower limb fat percentage (% trunk fat mass / % lower limb fat mass). Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Fat Mass Ratio as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: This secondary outcome measure assessed the ratio of semen:plasma concentration of etravirine in paired semen and plasma samples collected from 14 male participants at Week 4 of treatment with etravirine and fixed dose tenofovir/emtricitabine.

Measure: Pharmacokinetics of Etravirine in Genital Secretions of up to 10 Men and up to 10 Women at Week 4 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 4 weeks

Description: Change from baseline to follow-up in fat mass ratio was calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Fat mass ratio was calculated as the ratio of trunk fat percentage and lower limb fat percentage (% trunk fat mass / % lower limb fat mass). Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Fat Mass Ratio as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Population pharmacokinetics were calculated using sparse sampling. Plasma concentrations of etravirine measured in samples from participants who provided blood samples at multiple study visits, with variation in sampling times relative to dosing of etravirine used to cover the spectrum of the dosing schedule. Model simulations and fitting were performed with NONMEM ® 7.3. (ICON, plc) and model exploration was performed with Berkeley Madonna (Berkeley, CA, USA)

Measure: Population Pharmacokinetics of Etravirine 400 mg Once Daily, in Combination With Fixed-dose Emtricitabine-tenofovir Among Treatment-naïve HIV-1 Infected Adults

Time: At or after 4 weeks

Description: Population pharmacokinetics were calculated using sparse sampling. Plasma concentrations of etravirine measured in samples from participants who provided blood samples at multiple study visits, with variation in sampling times relative to dosing of etravirine used to cover the spectrum of the dosing schedule. Model simulations and fitting were performed with NONMEM ® 7.3. (ICON, plc) and model exploration was performed with Berkeley Madonna (Berkeley, CA, USA)

Measure: Population Pharmacokinetics of Etravirine 400 mg Once Daily, in Combination With Fixed-dose Emtricitabine-tenofovir Among Treatment-naïve HIV-1 Infected Adults: Etravirine AUC-24 Hours at Steady State

Time: At or after 4 weeks

7 Safety and Efficacy of Emtricitabine/Tenofovir Alafenamide as Part of Salvage Antiretroviral Regimens in Patients With Uncontrolled Viremia and Drug-Resistant HIV Infection

Background: HIV attacks the immune system. Antiretroviral therapy (ART) is a combination of drugs used for treating HIV infection. For some people, ART drugs stop working against their HIV. Researchers want to see if a different form of the drug tenofovir (an ART drug currently approved by the FDA), combined with another drug, may help people whose HIV is resistant to ART. This combination pill is called F/TAF Objective: To study the safety and efficacy of the drug F/TAF, when used with other ART, for people whose HIV infection has been hard to control with available medicines. Eligibility: People age 14 years and older who have HIV infection and are enrolled in the DOTCOM (14-I-0009) protocol. Design: Participants will be screened with physical exam, medical history, and blood and urine tests. Participants will stay in the hospital for at least 10 days. For the first 9 days, they will take F/TAF by mouth along with their usual ART drugs. In the hospital, they will repeat the screening tests. Participants will have a DEXA scan, an x-ray that measures calcium and other minerals in the bones. Participants will lie on a soft table while the scanner passes over the lower spine and hips. Participants will get a supply of F/TAF and some new ART drugs to take at home. Participants will have follow-up visits in 1, 2, 4, 8, and 12 weeks. After the 12-week visit, they will come back about every 3 months for about 1 year. At these visits, participants will repeat the screening tests. They will discuss any problems taking their ART drugs. They may have another DEXA scan.

NCT02556333
Conditions
  1. HIV
Interventions
  1. Drug: FTC/TAF

- Where neither TDF nor ABC are optimal NRTI options as defined by at least one of the following criteria: - Presence of the M184V mutation plus TDF-associated resistance mutations based on genotypic/phenotypic testing, specifically K65R alone, or with TAMs (such as 41L, 67N, 70R, 210W, 215Y/F, or 219Q/E) with or without other NRTI-associated mutations; or - FTC/TDF is not considered an option due to impaired renal function (eGFR by Cockroft-Gault equation [eGFR(CG)]=30-60 mL/min), or risk of renal impairment because of conditions such as uncontrolled hypertension, diabetes mellitus, or history of renal toxicity while receiving a TDF-based regimen; and where ABC/3TC is contraindicated (ie, presence of HLA B*5701 allele or history of hypersensitivity reaction to ABC), or is a suboptimal option (eg, presence of ABC-associated resistance mutation(s) or in patients with HBV co-infection). --- M184V --- --- K65R ---

Viral mutations (eg, K65R, multiple thymidine analog mutations (TAMs) can confer resistance or reduced susceptibility to TDF. --- K65R ---

Primary Outcomes

Description: An HIV RNA decline of >=0.5 log by day 10 will be considered to be an adequate virologic response, to proceed to the second phase of the study.

Measure: HIV RNA Change From Baseline to Day 10

Time: 10 days

8 A Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerance, Pharmacokinetics and Antiviral Activity of Amdoxovir and Zidovudine in Untreated HIV-1 Infected Subjects Currently Untreated

The purpose of this study is to determine the short term safety, tolerance, and antiviral effect of zidovudine (AZT) and amdoxovir (AMDX, DAPD) in combination, and whether the dosage for AZT can be reduced, potentially decreasing side effects, while maintaining antiviral effects. Study hypothesis: DADP in combination with AZT is safe and effective, and AZT dosing may be reduced, resulting in lower levels of AZT-monophosphate associated with toxicity and maintaining levels of AZT-triphosphate associated with efficacy.

NCT00432016
Conditions
  1. HIV Infections
Interventions
  1. Drug: zidovudine
  2. Drug: amdoxovir
  3. Procedure: pharmacokinetic sampling
MeSH:HIV Infections

Therefore, second line treatments that are currently in development should provide activity against resultant mutations, primarily M184V/I (17%) and much less commonly K65R (0 to 5%), and ideally prevent or be effective against mutations that may occur during second line therapy. --- M184V --- --- K65R ---

AZT offers anti-K65R activity which is believed to be conferred by the 3'-azido moiety containing pseudo-sugar structure and base components of AZT. --- K65R ---

Hence, AZT could potentially be incorporated to prevent the emergence of the K65R mutation that could limit the long-term benefit of DAPD. --- K65R ---

This 10 day, proof of principle, pharmacokinetic study will provide important information about reduced AZT dosing to support the development of an AZT/DAPD co-formulation which may prevent the emergence of K65R mutations. --- K65R ---

Primary Outcomes

Measure: Proportion of subjects in each arm with Grade 3 or greater treatment emergent adverse events (AE)

Measure: Plasma Cmax, Cmin, tmax, AUC0→τ, AUC0→∞, t1/2, CL/F of DAPD and AZT in each group at Days 1 and 10

Measure: Intracellular Cmax, Cmin, tmax, AUC0→τ, AUC0→∞, and t1/2 of DXG-TP, -MP and -DP and AZT-TP, -MP, and -DP at Days 1 and 10

Secondary Outcomes

Measure: Change in viral load (plasma HIV-1 RNA) from Baseline through Day 10

Measure: Correlate intracellular DXG-TP and AZT-TP with viral response, as measured by plasma HIV-1 RNA

Measure: Quantitate DXG, AZT, and GAZT in urine with and without DAPD

Measure: Characterize viral rebound (plasma HIV-1 RNA) following drug discontinuation for 48 hr

Measure: Measure CD4+ count changes from Baseline to Day 10

9 A Phase 3, Randomized, Open Label, Controlled Study of Lopinavir/Ritonavir and Lamivudine Versus Standard Therapy in Naïve HIV-1 Infected Subjects.

The purpose of this study is designed to compare the safety, tolerability, antiviral activity and immunological effect of lopinavir/ritonavir plus lamivudine (3TC) versus standard therapy with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus lopinavir/ritonavir in the treatment of naïve HIV-1 infected subjects.

NCT01237444
Conditions
  1. HIV Infection
Interventions
  1. Drug: lopinavir/ritonavir plus one nucleoside
  2. Drug: lopinavir /ritonavir plus two nucleosides
MeSH:HIV Infections

2. The presence of any of the following major mutations: V32I; I47V / A; L76V; V82A/F/T/S or the presence of two or more minor mutations at positions:10,20,24,33,46,50,53,54,63,71,73,84,90 is considered resistance to lopinavir/ritonavir. 3. The presence of mutation M184V/I and/or K65R is considered resistance to 3TC or FTC. --- V32I --- --- I47V --- --- L76V --- --- V82A --- --- M184V --- --- K65R ---

Primary Outcomes

Measure: • Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL in an intent-to-treat analysis at week 48

Time: 48 and 96 weeks

Secondary Outcomes

Description: Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL at week 24. Number and type of resistance mutations in case of virologic failure• CD4+ lymphocyte count and proportion evolution between baseline and week 24 and 48. Comparison of lipid profiles after 48 weeks Changes in quality of life, assessed by a validated questionnaire Treatment survival and interruptions. Frequency, type and severity of adverse events. Frequency of opportunistic infections (OI) and disease progression.

Measure: • Proportion of patients with HIV-1 RNA levels of less than 400 copies/mL at week 24 and at week 48

Time: 48 weeks

10 (COMEBACK): Biktarvy in PLWH But Not Retained in Care Coupled With a Strengths-based Case Management Approach to Assess Virologic Suppression Rates and Retention in Care, Along With Patient Reported Outcomes (PROS).

COMEBACK is an investigator-initiated, 48-week study. The study will be conducted in 100 persons living with HIV (PLWH) who have been off ART for two or more weeks. All enrolled participants will be prescribed Biktarvy, if determined appropriate upon review of past historical resistance tests, for use throughout the study period. Participants will also complete a series of Patient Reported Outcomes (PROs) at screening and be assigned one of three tiers of case management intervention (Piggyback, Got Your Back, Backbone), with each tier increasing in intensity regarding intervention techniques and options provided. Participants will be assessed for virologic suppression, retention in care, and PROS throughout study follow up and at study end.

NCT04519970
Conditions
  1. Hiv
Interventions
  1. Behavioral: Case Management

No history of primary integrase inhibitor mutations, >3 TAMs, K70E, Q151M, T69 insertion, or K65R + M184V/I on prior resistance testing 2. Drug-drug interactions with Biktarvy 3. Pregnancy 4. Unable or unwilling to provide consent for study participation 5. Any condition that, in the opinion of the Investigator of Record (IoR), would make participation in the study unsafe, complicate interpretation of outcome data, or otherwise interfere with achieving the study objective. --- K70E --- --- Q151M --- --- K65R ---

Primary Outcomes

Description: Number of patients with virologic suppression, defined as HIV RNA <50 copies/ml at week 24 RNA.

Measure: Virologic Suppression Rates

Time: 1 year

Description: Number of patients retained in study, defined as at least 2 visits or 2 HIV-1 RNA viral load reports occurring at least 3 months apart within the 12-month study time period

Measure: Retention in Care

Time: 1 year

Secondary Outcomes

Description: Favorable outcomes concerning health and and social related determinants as assessed by responses to a series of Patient Reported Outcomes at 6 and 12 months. See full list in attached documents.

Measure: Patient Reported Outcomes concerning social and health related barriers

Time: 1 year

11 Multicenter Study of Options for Second-Line Effective Combination Therapy (SELECT)

The study was conducted on people who were taking their first anti-HIV drug regimen (including an Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), a type of anti-HIV drug) but the drugs in this regimen were not doing a good job of fighting their HIV infection. The main purpose of this study was to compare two other anti-HIV drug regimens to see how well they fight HIV. The study also looked at how well participants tolerate the drug regimens and how safe they are. The study was designed to determine whether taking the combination of lopinavir/ritonavir (LPV/r) plus raltegravir (RAL) works as well as what is usually used for second-line therapy: LPV/r plus the best-available nucleoside (nucleotide) reverse transcriptase inhibitor (NRTI) combination. Testing a regimen that does not include any NRTIs was important because NRTIs may no longer work for patients who received them as part of their first treatment regimen.

NCT01352715
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: Lopinavir/ritonavir
  2. Drug: Lopinavir/ritonavir
  3. Drug: Raltegravir
  4. Drug: Emtricitabine/tenofovir disoproxil fumarate
  5. Drug: Abacavir/lamivudine/zidovudine
  6. Drug: Abacavir/lamivudine
  7. Drug: Lamivudine/zidovudine
  8. Drug: Abacavir
  9. Drug: Zidovudine
  10. Drug: Lamivudine

The most significant of these mutations include M184V, thymidine analogue mutations (TAMs), Q151M complex, and K65R. --- M184V --- --- Q151M --- --- K65R ---

The presence of K65R would result in resistance to most NRTIs (leaving only zidovudine (ZDV) and possibly abacavir (ABC) as active second-line options); the presence of multiple TAMs and/or Q151M alone or in complex with other mutations would also result in resistance to most NRTIs. --- K65R ---

Primary Outcomes

Description: The primary endpoint was time to virologic failure. Virologic failure was defined as confirmed viral load >400 copies/mL at or after week 24. The Kaplan-Meier estimate of the cumulative probability of virologic failure by week 48 was used.

Measure: Cumulative Probability of Virologic Failure by Week 48

Time: From study entry to week 48

Secondary Outcomes

Description: Change in CD4+ cell count was calculated as CD4+ cell count at week 48 minus CD4+ cell count at study entry.

Measure: Change in CD4+ Cell Count From Baseline to Week 48

Time: Study entry and week 48

Description: Mutations were defined as major IAS mutations in the IAS-USA July 2014 list. New mutations were those detected at virologic failure but not at baseline.

Measure: Number of Participants With HIV-1 Drug Resistance Mutations in Protease, Reverse Transcriptase, and Integrase in Participants With Virologic Failure at Baseline and at Time of Virologic Failure

Time: From study entry through to week 96

Description: The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs.

Measure: Number of Participants With Grade 3 or Higher Adverse Event (AE) at Least One Grade Higher Than Baseline

Time: From start of randomized treatment to off randomized treatment (up to 96 weeks)

Description: Discontinuation of randomized treatment for toxicity included participant decision to discontinue for low grade toxicity. Within class NRTI changes were not considered discontinuations.

Measure: Number of Participants Discontinuing Randomized Treatment for Toxicity

Time: From Start of Randomized Treatment to Off Randomized Treatment (up to 96 weeks)

Description: AIDS-defining events were those recognized by the Centers for Disease Control (CDC) and World Health Organization (WHO)

Measure: Number of Participants With a New AIDS-defining Events or Death

Time: From study entry throughout follow-up (up to 96 weeks)

Description: Serious non-AIDS diagnoses were based on ACTG Appendix 60 Diagnosis Codes

Measure: Number of Participants With a Targeted Serious Non-AIDS-defining Event or Death

Time: From study entry throughout follow-up (up to 96 weeks)

Description: The percentage of total study time that participants were in hospital.

Measure: Percentage of Time Spent in Hospital

Time: From study entry throughout follow-up (up to 96 weeks)

Description: Fasting was for 8 hours and the metabolic panel was drawn locally.

Measure: Changes in Fasting Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides, and Glucose From Baseline

Time: Study entry and week 48

12 Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples

Randomized, blinded, placebo-controlled trial to demonstrate if pre-exposure prophylaxis decreases HIV-1 acquisition among HIV-1 uninfected individuals within HIV-1 discordant couples.

NCT00557245
Conditions
  1. HIV-1 Infections
  2. HIV Infections
Interventions
  1. Drug: Tenofovir Disoproxil Fumarate (TDF)
  2. Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
  3. Drug: Placebo
MeSH:Infection Communicable Diseases HIV Infections

HIV-1 resistance as measured by the number of seroconverters who had an HIV-1 reverse transcriptase mutation (K65R, K70E, M184I, or M184V) conferring resistance to TDF or FTC. --- K65R ---

Primary Outcomes

Description: The efficacy of once daily PrEP in preventing HIV-1 acquisition among uninfected heterosexuals in HIV-1 discordant partnerships, measured by calculating the HIV incidence per 100 person-years in each of three arms.

Measure: Incidence of HIV-1 Seroconversion Among HIV-1 Uninfected Participants

Time: Up to 36 months

Description: Safety of daily TDF or FTC/TDF among HIV-1 uninfected individuals randomized to TDF or FTC/TDF compared to those randomized to placebo measured as the number of participants with Serious Adverse Events (SAEs) during follow-up.

Measure: Number of Participants With Serious Adverse Events (SAEs)

Time: Up to 36 months

Secondary Outcomes

Description: Adherence to study medication as assessed by pill count at follow-up visits. We assessed the total number of doses taken of the total dispensed doses.

Measure: Study Drug Adherence: Total Number of Study Drug Doses Taken of the Total Dispensed Doses.

Time: Up to 36 months

Description: Adherence to study drug measured as the percentage of visits when participants reported missing 1) any dose of study drug in the prior month and 2) 2 or more consecutive doses of study drug.

Measure: Study Drug Adherence: Self-reported Missed Doses of Study Drug

Time: Up to 36 months

Description: HIV-1 resistance as measured by the number of seroconverters who had an HIV-1 reverse transcriptase mutation (K65R, K70E, M184I, or M184V) conferring resistance to TDF or FTC. These mutation types were pre-defined. Plasma samples for resistance testing were collected at the visit seroconversion was first detected and again at a visit within 1 month of seroconversion. Mutations detected at either of those visits are reported. Both seroconverters found to have a resistance mutation had been HIV infected at enrollment (TDF arm: n=1; FTC-TDF arm: n=1).

Measure: Number of Seroconverters With an HIV-1 Mutation Conferring Resistance to TDF or FTC

Time: Up to 36 months

Description: Prevalence of STIs measured as the number of participants with a positive test result for N. gonorrhoeae, C. trachomatis, or T. vaginalis during follow-up. Participants were tested for STIs at annual follow-up visits and at intervening visits at which the participant presented with symptoms of an STI. Assessment for symptomatic sexually transmitted infections was conducted quarterly. N. gonorrhoeae and C. trachomatis testing were by APTIMA Combo 2 (Gen-Probe) or COBAS Amplicor (Roche Diagnostics). T. vaginalis testing was by APTIMA TV TMA (Gen-Probe) or In Pouch TV (Biomed Diagnostics).

Measure: Number of Participants With a Sexually Transmitted Infection (STI) During Follow-up

Time: Up to 36 months

Description: Sexual risk behavior of participants, measured as the percentage of visits when participants reported having unprotected sex during follow-up.

Measure: Prevalence of Unprotected Sex During Follow-up

Time: Up to 36 months

Description: Infant outcomes measured as the number of live-born infants born to female participants taking study drug that had any congenital anomalies.

Measure: Congenital Abnormalities Among Infants Born to Female Participants Taking Study Drug.

Time: Up to 36 months

Description: The slope of the linear model of the growth of infants (length) during the entirety of follow-up. The length of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.

Measure: Length Among Infants Born to Female Participants Taking Study Drug

Time: up to 12 months

Description: The slope of the linear model of the growth of infants (weight) during the entirety of follow-up. The weight of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.

Measure: Weight Among Infants Born to Female Participants Taking Study Drug

Time: up to 12 months

Description: The slope of the linear model of the growth of infants (head circumference) during the entirety of follow-up. The head circumference of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.

Measure: Head Circumference Among Infants Born to Female Participants Taking Study Drug

Time: up to 12 months

13 Phase II, Open-Label,Randomised, Comparator Study of Substitution w/Tenofovir or Abacavir in HIV-1 Infected Individuals, w/Viral Load Less 50 Copies/mL, Receiving a Thymidine Analogue (Zidovudine or Stavudine) as Part of HAART.

This 48 week study is designed to compare the substitution of the thymidine analogues zidovudine (ZDV) or stavudine (D4T) with either tenofovir DF or abacavir, in patients treated with highly active antiretroviral therapy (HAART), and show improved outcomes on total limb fat mass, improved body shape by dual energy x-ray absorptiometry (DEXA) and computed tomography (CT) scans and improved cholesterol and tryglicerides.

NCT00270556
Conditions
  1. HIV
Interventions
  1. Drug: tenofovir disoproxil fumarate
  2. Drug: Abacavir

Subjects with no known K65R, 69S mutations or 3 or more thymidine analogue mutations. --- K65R ---


14 Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir in Treatment-experienced Patients: Quality Control Monitoring of a Treatment Simplification Strategy

The study aims to assess the safety and efficacy of darunavir 800mg plus the co-formulated elvitegravir/cobicistat/tenofovir disoproxil fumarate (DF)/emtricitabine (Stribild) tablet as a simplification strategy for the treatment of HIV infection in HIV-infected subjects who have had previous antiretroviral treatment experience with multiple-drug regimens. We hypothesize that elvitegravir/cobicistat/tenofovir DF/emtricitabine with darunavir will offer a safe and efficacious treatment simplification strategy for HIV positive patients currently receiving multiple-drug regimens to control their HIV infection.

NCT02199613
Conditions
  1. HIV Infection
Interventions
  1. Drug: Treatment simplification
MeSH:HIV Infections

- Evidence of clinically significant resistance to tenofovir on any previous genotype tests: K65R mutation, or 3 or more thymidine-analogue associated mutations (TAMS) compromising tenofovir activity - Evidence of resistance mutations significantly compromising darunavir activity on any previous genotypic tests - Current use of any nonnucleoside reverse transcriptase inhibitor (NNRTI) - Pregnancy or breast-feeding - Contraindications to tenofovir/FTC, elvitegravir, or cobicistat (e.g. --- K65R ---

Primary Outcomes

Description: Proportion of individuals with plasma HIV RNA <200copies/mL at 12 weeks following regimen switch

Measure: Plasma HIV RNA

Time: 12 weeks

Secondary Outcomes

Description: Proportion of individuals with plasma HIV RNA < 50 copies/mL at weeks 12, 24 and 48 post switch

Measure: plasma HIV RNA

Time: weeks 12, 24 and 48

Description: Proportion of individuals with plasma HIV RNA < 200 copies/mL at week 24 and 48 post switch

Measure: plasma HIV RNA

Time: week 24 and 48

Description: Change in CD4 cell count, CD4% and CD4/CD8 ratio from study baseline to 12, 24 and 48 weeks after switch.

Measure: CD4 cell count, CD4% and CD4/CD8 ratio

Time: 12, 24 and 48 weeks

Description: Change in serum creatinine and eGFR from baseline to 12, 24 weeks and 48 weeks.

Measure: serum creatinine and estimated glomerular filtration rate (eGFR)

Time: 12, 24, and 48 weeks

Description: Proportion of adverse events experienced necessitating switch to original regimen

Measure: Adverse event discontinuations

Time: 48 weeks

Description: Changes in fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP) between baseline and 24 and 48 weeks.

Measure: fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP)

Time: 24 and 48 weeks

Description: Change in darunavir trough concentration from baseline to week 2 for individuals receiving darunavir at baseline

Measure: Darunavir plasma concentration

Time: week 2

Description: Changes in HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores) between baseline and weeks 24 and 48 following switch.

Measure: HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores)

Time: weeks 24 and 48

Description: Changes in antiretroviral adherence from baseline to 24 and 48 weeks. Adherence will be assessed using two measures: the ACTG treatment adherence questionnaire and the Medication adherence self-report inventory (MASRI).

Measure: Adherence

Time: 24 and 48 weeks

Description: Elvitegravir concentrations will be measured at day 14

Measure: Elvitegravir plasma concentrations

Time: Day 14

Description: Adverse events necessitating a resumption of the previous antiretroviral regimen, and all serious adverse events will be recorded.

Measure: Adverse events

Time: 48 weeks

15 A Randomized, Open Label, Phase 4 Study Evaluating the Renal Effect of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF or Other Tenofovir DF-containing Regimens (Ritonavir-boosted Atazanavir Plus Emtricitabine/Tenofovir DF or Efavirenz/Emtricitabine/Tenofovir DF) Compared to Ritonavir-boosted Atazanavir Plus Abacavir/Lamivudine in Antiretroviral Treatment-naïve HIV-1 Infected Adults With eGFR ≥70 mL/Min

The primary objective of this study is to assess glomerular function before and during administration of stribild (STB; elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) or a regimen containing TDF without cobicistat (COBI) as ritonavir (RTV)-boosted atazanavir (ATV/r) plus truvada (TVD; FTC/TDF) or atripla (ATR; efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF)) compared to a regimen containing neither TDF nor COBI as ATV/r plus abacavir/lamivudine (ABC/3TC) via determination of actual glomerular filtration rate (aGFR) using iohexol (a probe GFR marker) plasma clearance and estimated (calculated) glomerular filtration rate (eGFR).

NCT02246998
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: STB
  2. Drug: TVD
  3. Drug: ATR
  4. Drug: RTV
  5. Drug: ATV
  6. Drug: ABC/3TC
  7. Drug: Iohexol

The most severe graded abnormality from all tests was counted for each participant.. Key Inclusion Criteria: - Treatment naïve - Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at Screening - CD4 cell count > 200 cells/µL - Screening genotype report provided by the site must show sensitivity to FTC, TDF, EFV, ABC, 3TC, ATV and absence of study drug resistance mutations that include K65R, K70E and M184V in RT - Estimated GFR ≥ 70 mL/min - Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 5 × upper limit of normal (ULN) - Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), or normal direct bilirubin - Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL) - Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN) - Normal electrocardiogram (ECG) or not clinically significant if abnormal ECG - Not pregnant or non-lactating females of non-childbearing potential. --- K65R ---

Key Inclusion Criteria: - Treatment naïve - Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at Screening - CD4 cell count > 200 cells/µL - Screening genotype report provided by the site must show sensitivity to FTC, TDF, EFV, ABC, 3TC, ATV and absence of study drug resistance mutations that include K65R, K70E and M184V in RT - Estimated GFR ≥ 70 mL/min - Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 5 × upper limit of normal (ULN) - Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), or normal direct bilirubin - Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL) - Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN) - Normal electrocardiogram (ECG) or not clinically significant if abnormal ECG - Not pregnant or non-lactating females of non-childbearing potential. --- K65R ---

Primary Outcomes

Measure: Actual Glomerular Filtration Rate (aGFR) Using Iohexol Plasma Clearance (CLiohexol) at Week 24

Time: Week 24

Description: GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFR = (140 - age) * (mass in kg) * (0.85 if female) divided by 72 * serum creatinine in mg/dL

Measure: Estimated GFR (eGFR) Calculated by Cockcroft-Gault Formula at Week 24

Time: Week 24

Description: MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender. eGFR (mL/min/1.73 m^2) = 186 * (Scr)^-1.154 * (Age)^(-0.203) * (0.742 if female) * (1.212 if black). Scr = serum creatinine in mg/dL

Measure: Estimated GFR Calculated by Modification of Diet in Renal Disease (MDRD) Formula at Week 24

Time: Week 24

Secondary Outcomes

Measure: Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Urine Glucose (by Dipstick)

Time: Up to 24 weeks plus 30 days

Measure: Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Serum Glucose (Fasting)

Time: Up to 24 weeks plus 30 days

Measure: Percentage Change From Baseline in Urine Albumin to Creatinine Ratio (mg/g) at Week 24

Time: Baseline; Week 24

Measure: Percentage Change From Baseline in Urine Protein to Creatinine Ratio (mg/g) at Week 24

Time: Baseline; Week 24

Measure: Percentage Change From Baseline in Urine β2-microglobulin to Creatinine Ratio (µg/g) at Week 24

Time: Baseline; Week 24

Measure: Percentage Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio (µg/g) at Week 24

Time: Baseline; Week 24

Description: Cmax is defined as the maximum observed concentration of drug in plasma.

Measure: Pharmacokinetic (PK) Parameter: Cmax for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: Tmax is defined as the time of Cmax.

Measure: PK Parameter: Tmax for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: Clast is defined as the last observable concentration of drug.

Measure: PK Parameter: Clast for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: Tlast is defined as the time of Clast. Plasma samples for PK analysis were collected out to 10 hours postdose, and the predose concentration was used as a surrogate for the 24 hour concentration for PK parameter generation.

Measure: PK Parameter: Tlast for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: Ctau is defined as the observed drug concentration at the end of the dosing interval.

Measure: PK Parameter: Ctau for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: λz is defined as the terminal elimination rate constant.

Measure: PK Parameter: λz for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).

Measure: PK Parameter: AUCtau for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Measure: PK Parameter: t1/2 for COBI

Time: Predose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: Cmax for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: Tmax for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: Clast for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: Plasma samples for PK analysis were collected out to 10 hours postdose, and the predose concentration was used as a surrogate for the 24 hour concentration for PK parameter generation.

Measure: PK Parameter: Tlast for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: Ctau for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: AUCtau for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: λz for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: t1/2 for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: Cmax for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: Tmax for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: Clast for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: Plasma samples for PK analysis were collected out to 10 hours postdose, and the predose concentration was used as a surrogate for the 24 hour concentration for PK parameter generation.

Measure: PK Parameter: Tlast for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: Ctau for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: λz for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: AUCtau for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Measure: PK Parameter: t1/2 for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

Description: AUC inf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

Measure: PK Parameter: AUCinf for Iohexol

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" on Day 1 and Weeks 4, 8, 16, and 24

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL Week 24 as Determined by Snapshot Algorithm

Time: Week 24

Measure: Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count at Week 24

Time: Baseline; Week 24

Description: Incidences of adverse events and laboratory abnormalities will be summarized.

Measure: Percentage of Participants Experiencing Adverse Events (AEs)

Time: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days)

Description: Graded laboratory abnormalities were defined as values that increased at least one toxicity grade from predose at any postdose up to the last dose date of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant.

Measure: Percentage of Participants Experiencing Treatment Emergent (TE) Grade 3 or 4 Laboratory Abnormalities

Time: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days)

16 Effect of SwitChing AtriPla to Eviplera on Neurocognitive and Emotional Functioning, ESCAPE Study

This study will evaluate the effects of switching Atripla to Eviplera on neurocognition measured by neuropsychological testing and functional MRI

NCT02308332
Conditions
  1. Neurocognitive Decline
  2. HIV Associated Neurocognitive Disorder
Interventions
  1. Drug: Eviplera
MeSH:Neurocognitive Disorders

Differences in mean changes between baseline and end of study, as well as between the two study groups will be calculated using a paired T-test.. Inclusion Criteria: - Male, between 30 and 50 years - HIV-1 RNA < 50 copies/mL on screening visit - on Atripla continuously for ≥6 months preceding the screening visit - Have a HIV genotype prior to starting cART with Atripla with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y - Negative TPHA or VDRL < 12 months prior to the screening visit - no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. --- K65R ---

Inclusion Criteria: - Male, between 30 and 50 years - HIV-1 RNA < 50 copies/mL on screening visit - on Atripla continuously for ≥6 months preceding the screening visit - Have a HIV genotype prior to starting cART with Atripla with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y - Negative TPHA or VDRL < 12 months prior to the screening visit - no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. --- K65R ---

Primary Outcomes

Description: Patients will undergo a neuropsychological test battery where multiple standardized test will be undertaken to assess 7 different domains; Verbal Fluency, Executive Functioning, Speed of Information Processing, Learning, Memory, Attention/Working Memory, Motor skills. Raw scores can be calculated per domain and as a composite score. Differences in mean changes in composite score between baseline and end of study will be assessed with a paired T-test. A p-value <0.05 will be considered statistically significant. Within-arm changes will be assessed using Wilcoxon signed rank tests, and between-group comparisons will be evaluated with Wilcoxon rank sum tests. Multivariate analyses will be performed to analyse differences in the primary endpoints between the study groups.

Measure: To evaluate the neurocognitive performance as measured by neuropsychological test composite score after 12 weeks in stable HIV-infected patients switched from Atripla to Eviplera compared to a control group of patients on Atripla.

Time: 12 weeks

Secondary Outcomes

Description: The aim is to investigate if there is a correlation between improvement on neuropsychological test scores after 12 weeks of Eviplera therapy, and changes on fMRI after 12 weeks of Eviplera therapy. If there is a correlation, that means fMRI could be used to evaluate neurocognitive decline. Basically, we will asses if there is a correlation between ∆neuropsychological score and ∆fMRI-score. Because this is ordinal data, we will use a Spearman rank-order correlation to calculate a correlation-coefficient.

Measure: to assess the correlation between neurocognitive improvement (neuropsychological evaluation) and functional imaging (fMRI) after switching Atripla to Eviplera

Time: 12 weeks

Description: The aim is if an improvement in neuropsychological test scores after 12 weeks of Eviplera therapy is correlated with an improvement of quality of life. Basically, we will assess if there is a correlation between ∆neuropsychological score and ∆SF-36 total score. Because this is ordinal data, we will use a Spearman rank-order correlation to calculate a correlation-coefficient.

Measure: to evaluate correlation between neurocognitive performance and health related quality of life measured by SF-36 total score after switching from Atripla to Eviplera.

Time: 12 weeks

Measure: to assess the emotional functioning measured by HADS total score after switching Atripla to Eviplera by using a paired T-test to calculate differences in mean changes between baseline and end of study

Time: 12 weeks

Measure: to assess USER-P (total scores) after switching Atripla to Eviplera

Time: 12 weeks

Description: With this study, we want to investigate the effect of switching Efavirenz (as a component of Atripla) to Rilpivirine (as a component of Eviplera) on neurocognition. Our hypothesis is that neurocognition (as measured by neuropsychological testing scores) will improve when switching from Efavirenz (as a component of Atripla). If that is the case, hypothetically a lower or higher drug level of Efavirenz (as a component of Atripla) could have an effect on neurocognition (as measured by neuropsychological test scores). We will assess the correlation between drug level of Efavirenz or Rilpivirine and changes in neurocognitive function as measured by neuropsychological testing, and fMRI changes by regression analyses using drug levels as an independent variable and neuropsychological test scores as a dependent variable.

Measure: to assess drug levels of Efavirenz (as a component of Atripla) and Rilpivirin (as a component of Eviplera) in relation to changes in neurocognitive performance and fMRI in both patient groups.

Time: 12 weeks

Description: In our study, we will use the PROMIS instruments Anxiety, Depression, Sleep disturbance and Satisfaction with social roles and activities. These are all short forms containing 8 questions or statements. Patients are asked to rate the questions from 1-5 into which extent they believe them to be true; 1 being not at all and 5 being very much. For each short form, a score will be calculated by adding the values of the response to each question. PROMIS provides a score conversion table where the score can be translated into a T-score. This rescales the patient's score into a standardized score with a mean of 50 and a standard deviation of 10. In order to provide these results, PROMIS uses a calibration sample containing data from over 21000 respondents. Differences in mean changes between baseline and end of study, as well as between the two study groups will be calculated using a paired T-test.

Measure: to evaluate the usefulness of PROMIS instruments in HIV research

Time: 12 weeks

17 Switch to a Completely ONce Daily Regimen Containing Emtricitabine/Tenofovir - Fixed Dose Combination Plus Third QD Partner: "SONETT"

There is an unmet medical need for potent ART regimens that make adherence to treatment even easier due to QD dosing, offer a good tolerability profile and fit into the daily life of patients.

NCT00323687
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: Truvada
MeSH:Infection

Inclusion Criteria: Adult patients (over 18 years of age) of any ethnic group without restricted legal competence and who are capable of following the study instructions HIV-1 infection documented by confirmed positive HIV-1 antibody test and/or positive PCR for HIV-1 RNA Stable (no interruption or change of regimen in last 3 months) AZT-and 3TC-containing regimen > 3 months No documented prior virologic failure (virological failure defined as 2 consecutive measurements 4 weeks apart with viral load of HIV-RNA > 400 copies/mL while on ART) CD4+ counts > 50 cells/µL Viral load < 50 copies/mL Karnofsky performance status ≥ 80% For women with childbearing potential, negative urine pregnancy test at Screening visit Exclusion Criteria: Serum phosphate level < 0.65 mmol/L Documented active opportunistic infections Subjects with previously documented K65R, 69S mutations or 3 or more thymidine analogue mutations Documented active malignant disease (excluding Kaposi sarcoma limited to the skin) Female of childbearing potential not willing to use a barrier method of contraception during heterosexual intercourse during the duration of study Women who are pregnant or breast feeding Known history of drug, medication or alcohol abuse within the last 12 months preceding the study Simultaneous participation in another study with an investigational drug or within less than one month prior to this study Inability or not willing to meet the requirements of the protocol History of seizures, central nervous system disorders or psychiatric disability thought to be clinically significant in the opinion of the investigator Limited mental capacity to the extent that he/she cannot provide informed consent or information regarding adverse events of the study medication Renal disease (creatinine clearance < 50 ml/min according to Cockroft_Gault formula) or severe hepatic, respiratory or cardiovascular disease Patients who have previously been enrolled into this study Contraindication for one of the study substances. --- K65R ---

Primary Outcomes

Measure: Proportion of patients with HIV RNA < 400 and with HIV RNA < 50 copies/mL at Week 48

Time: Week 48

Secondary Outcomes

Measure: Proportion of patients with HIV RNA < 400 and with HIV RNA < 50 copies/mL at Week 24

Time: 24 weeks

Measure: Time to failure or ART discontinuation. Virological failure is defined as 2 consecutive measurements 4 weeks apart with viral load of HIV-RNA > 400 copies/mL

Time: Up to 48 weeks

18 Evolution of L74V or K65R Mutations in VIremic Subjects on TDF or ABC (EVITA)

This is a multicenter, open-label, non-randomized, dual-arm pilot study to investigate the prevalence of the reverse transcriptase (RT) resistance mutations, K65R/x or L74V/x, in HIV-1 plasma from subjects experiencing confirmed first-time incomplete virologic suppression during treatment with an initial antiretroviral (ARV) regimen consisting of at least 12 weeks of TDF or ABC + emtricitabine (FTC) or lamivudine (3TC) + non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Subjects will be followed until a substantial loss of virologic or immunologic control requires a treatment switch. Confirmed first-time incomplete virologic suppression is defined as an initial plasma HIV-1 RNA response < 400 copies/mL, and subsequent virologic rebound > 400 copies/mL measured at two consecutive times. Subjects will have a screening genotype to establish adherence to their non-suppressive TDF- or ABC-containing regimen by the presence of M184V (or other treatment-related primary) mutation and to demonstrate that the evolution of treatment-emergent RT mutations can be characterized. Twenty subjects (a maximum of 10 per arm) will be enrolled at 10-20 United States (U.S.) sites. If fewer than 20 subjects can be enrolled, the study may be discontinued early by the sponsor. Equal numbers of subjects on Arm A versus Arm B will be a goal.

NCT00312169
Conditions
  1. HIV Infections
MeSH:HIV Infections

Evolution of L74V or K65R Mutations in VIremic Subjects on TDF or ABC (EVITA). --- L74V --- --- K65R ---

Evolution of L74V or K65R Mutations in VIremic Subjects on Tenofovir Disoproxil Fumarate (TDF) or Abacavir (ABC) (EVITA) This is a multicenter, open-label, non-randomized, dual-arm pilot study to investigate the prevalence of the reverse transcriptase (RT) resistance mutations, K65R/x or L74V/x, in HIV-1 plasma from subjects experiencing confirmed first-time incomplete virologic suppression during treatment with an initial antiretroviral (ARV) regimen consisting of at least 12 weeks of TDF or ABC + emtricitabine (FTC) or lamivudine (3TC) + non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). --- L74V --- --- K65R ---

Evolution of L74V or K65R Mutations in VIremic Subjects on Tenofovir Disoproxil Fumarate (TDF) or Abacavir (ABC) (EVITA) This is a multicenter, open-label, non-randomized, dual-arm pilot study to investigate the prevalence of the reverse transcriptase (RT) resistance mutations, K65R/x or L74V/x, in HIV-1 plasma from subjects experiencing confirmed first-time incomplete virologic suppression during treatment with an initial antiretroviral (ARV) regimen consisting of at least 12 weeks of TDF or ABC + emtricitabine (FTC) or lamivudine (3TC) + non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). --- L74V --- --- K65R --- --- K65R ---

Exclusion Criteria: 1. Subjects with screening HIV-1 genotype that is wild-type or contains the resistance mutations K65R/x or L74V/x. --- K65R ---

HIV Infections HIV Infections This is a multicenter, open-label, non-randomized, dual-arm pilot study to investigate the prevalence of the RT resistance mutations, K65R/x or L74V/x, in HIV-1 plasma from subjects experiencing confirmed first-time incomplete virologic suppression during treatment with an initial ARV regimen consisting of at least 12 weeks of TDF or ABC + FTC or 3TC + NNRTI or PI. --- K65R ---

Exclusion Criteria 1. Subjects with screening HIV-1 genotype that is wild-type or contains the resistance mutations K65R/x or L74V/x. --- K65R ---


19 Antiretroviral Treatment Guided by Proviral Genotype: Pilot Trial of Proof of Concept.

Phase IIa, open clinical trial, pilot, single arm and proof of concept.

NCT03539224
Conditions
  1. HIV-1-infection
Interventions
  1. Drug: Dolutegravir (DTG)
  2. Drug: Lamivudine (3TC)

For those included in group 1 (20 patients): No previous history of virological failure with ART regimen that included 3TC or FTC or previous virological failure had a population genotype without M184V/I or K65R/E/N mutations. --- M184V --- --- K65R ---

For those included in group 2 (20 patients): previous history of virological failure with ART regimen that included 3TC or FTC and historical genotype with M184V/I or K65R/E/N mutations. --- M184V --- --- K65R ---

Detection of any of the following mutations in proviral DNA in peripheral blood by conventional sequencing: M184V/I or K65R/E/N. --- M184V --- --- K65R ---

Half of the participants will have history of failure with 3TC or FTC and M184V/I or K65R/E/N mutations in previous plasma genotypes, although to be eligible these mutations cannot be detectable at study entry in proviral DNA. --- M184V --- --- K65R ---

Primary Outcomes

Description: - Efficacy: Proportion of patients with undetectable viral load (<50 copies / mL) at 48 weeks of follow-up, according to the FDA snapshot algorithm in the population "by intention to treat-exposed". The intention-to-treat population includes all patients who have received at least one dose of DTG and 3TC.

Measure: Proportion of patients with undetectable viral load (<50 copies / mL) at 48 weeks

Time: Week 48

Secondary Outcomes

Description: Proportion of patients with viral load <50 copies/ml at week 24, according to the FDA snapshot algorithm in the population "by intention to treat-exposed".

Measure: Proportion of patients with virological failure at 24 weeks

Time: Week 24

Description: Proportion of patients with virological failure at week 48 according to the FDA snapshot algorithm.

Measure: Proportion of patients with virological failure at 48 weeks

Time: Week 48

Description: Incidence of adverse events and discontinuation of treatment due to toxicity or intolerance.

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time: Since baseline visits to week 48

Description: Incidence of genotypic resistance mutations in patients with virological failure at week 48. Description and frequency of genotypic resistance mutations.

Measure: Evaluation of the appearance of genotypic resistance mutations (1)

Time: Week 48

20 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Tenofovir DF as Part of an Optimized Antiretroviral Regimen in HIV-1-Infected Adolescents

The purpose of this study is to assess the safety and efficacy of tenofovir disoproxil fumarate (tenofovir DF; TDF) plus a genotype-guided optimized background regimen (OBR) compared to placebo plus OBR in the treatment of human immunodeficiency virus type 1 (HIV-1) infected antiretroviral treatment-experienced adolescents with plasma HIV-1 ribonucleic acid (RNA) levels greater than or equal to 1000 copies/mL.

NCT00352053
Conditions
  1. HIV Infections
Interventions
  1. Drug: Tenofovir DF
  2. Drug: Placebo
MeSH:HIV Infections

The virologic failure rate was estimated from Kaplan-Meier product limit method by including all HIV-1 RNA data collected during the double-blind phase.. Major Inclusion Criteria: - Weight ≥ 35 kg - Documented laboratory diagnosis of HIV infection - Plasma HIV-1 RNA ≥ 1000 copies/mL - Prior antiretroviral treatment experience with at least 2 antiretroviral drug classes - Naive to tenofovir DF - Absence of K65R mutation on genotypic testing Exclusion Criteria: - Patients requiring didanosine in background regimen - Prior history of significant renal disease - Prior history of significant bone disease Major Inclusion Criteria: - Weight ≥ 35 kg - Documented laboratory diagnosis of HIV infection - Plasma HIV-1 RNA ≥ 1000 copies/mL - Prior antiretroviral treatment experience with at least 2 antiretroviral drug classes - Naive to tenofovir DF - Absence of K65R mutation on genotypic testing Exclusion Criteria: - Patients requiring didanosine in background regimen - Prior history of significant renal disease - Prior history of significant bone disease HIV Infections HIV Infections This is a 48-week, randomized, double-blind, placebo-controlled, multicenter study of the safety and efficacy of tenofovir DF as part of an optimized antiretroviral regimen in HIV-1 infected adolescents (12 years to < 18 years of age) who are failing their current antiretroviral regimen and have HIV-1 RNA levels ≥ 1000 copies/mL at screening. --- K65R ---

The virologic failure rate was estimated from Kaplan-Meier product limit method by including all HIV-1 RNA data collected during the double-blind phase.. Major Inclusion Criteria: - Weight ≥ 35 kg - Documented laboratory diagnosis of HIV infection - Plasma HIV-1 RNA ≥ 1000 copies/mL - Prior antiretroviral treatment experience with at least 2 antiretroviral drug classes - Naive to tenofovir DF - Absence of K65R mutation on genotypic testing Exclusion Criteria: - Patients requiring didanosine in background regimen - Prior history of significant renal disease - Prior history of significant bone disease Major Inclusion Criteria: - Weight ≥ 35 kg - Documented laboratory diagnosis of HIV infection - Plasma HIV-1 RNA ≥ 1000 copies/mL - Prior antiretroviral treatment experience with at least 2 antiretroviral drug classes - Naive to tenofovir DF - Absence of K65R mutation on genotypic testing Exclusion Criteria: - Patients requiring didanosine in background regimen - Prior history of significant renal disease - Prior history of significant bone disease HIV Infections HIV Infections This is a 48-week, randomized, double-blind, placebo-controlled, multicenter study of the safety and efficacy of tenofovir DF as part of an optimized antiretroviral regimen in HIV-1 infected adolescents (12 years to < 18 years of age) who are failing their current antiretroviral regimen and have HIV-1 RNA levels ≥ 1000 copies/mL at screening. --- K65R --- --- K65R ---

Primary Outcomes

Description: DAVG24 was defined as the time-weighted average between the first postbaseline value through the last value up to Week 24 minus the baseline value. DAVG24 was calculated using the trapezoidal rule with all available postbaseline data minus the baseline value. Data for participants who discontinued the randomized (double-blind) phase of the study early were included up until the point of study discontinuation (missing data not imputed).

Measure: Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA

Time: Baseline to 24 Weeks

Secondary Outcomes

Description: DAVG48 was defined as the time-weighted average between the first postbaseline value through the last value up to Week 48 minus the baseline value. DAVG48 was calculated using the trapezoidal rule with all available postbaseline data minus the baseline value. Data for participants who discontinued the double-blind phase of the study early were included up until the point of discontinuation from the study (ie, missing data were not imputed).

Measure: Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA

Time: Baseline to 48 weeks

Measure: Change From Baseline to Week 24 in HIV-1 RNA

Time: Baseline to 24 weeks

Measure: Change From Baseline to Week 48 in HIV-1 RNA

Time: Baseline to 48 weeks

Measure: Change From Baseline to Week 96 in HIV-1 RNA

Time: Baseline to 96 weeks

Measure: Change From Baseline to Week 144 in HIV-1 RNA

Time: Baseline to 144 weeks

Measure: Change From Baseline to Week 192 in HIV-1 RNA

Time: Baseline to 192 weeks

Measure: Change From Baseline to Week 240 in HIV-1 RNA

Time: Baseline to 240 weeks

Measure: Change From Baseline to Week 288 in HIV-1 RNA

Time: Baseline to 288 weeks

Description: No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.

Measure: Change From Baseline to Week 336 in HIV-1 RNA

Time: Baseline to 336 weeks

Measure: Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count

Time: Baseline to 24 weeks

Measure: Change From Baseline to Week 48 in CD4 Count

Time: Baseline to 48 weeks

Measure: Change From Baseline to Week 96 in CD4 Count

Time: Baseline to 96 weeks

Measure: Change From Baseline to Week 144 in CD4 Count

Time: Baseline to 144 weeks

Measure: Change From Baseline to Week 192 in CD4 Count

Time: Baseline to 192 weeks

Measure: Change From Baseline to Week 240 in CD4 Count

Time: Baseline to 240 weeks

Measure: Change From Baseline to Week 288 in CD4 Count

Time: Baseline to 288 weeks

Description: No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.

Measure: Change From Baseline to Week 336 in CD4 Count

Time: Baseline to 336 weeks

Description: CD4 percentage is the percentage of total lymphocytes that are CD4 cells.

Measure: Change From Baseline to Week 24 in CD4 Percentage

Time: Baseline to 24 weeks

Description: CD4 percentage is the percentage of total lymphocytes that are CD4 cells.

Measure: Change From Baseline to Week 48 in CD4 Percentage

Time: Baseline to 48 weeks

Description: CD4 percentage is the percentage of total lymphocytes that are CD4 cells.

Measure: Change From Baseline to Week 96 in CD4 Percentage

Time: Baseline to 96 weeks

Description: CD4 percentage is the percentage of total lymphocytes that are CD4 cells.

Measure: Change From Baseline to Week 144 in CD4 Percentage

Time: Baseline to 144 weeks

Description: CD4 percentage is the percentage of total lymphocytes that are CD4 cells.

Measure: Change From Baseline to Week 192 in CD4 Percentage

Time: Baseline to 192 weeks

Description: CD4 percentage is the percentage of total lymphocytes that are CD4 cells.

Measure: Change From Baseline to Week 240 in CD4 Percentage

Time: Baseline to 240 weeks

Description: CD4 percentage is the percentage of total lymphocytes that are CD4 cells.

Measure: Change From Baseline to Week 288 in CD4 Percentage

Time: Baseline to 288 weeks

Description: No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.

Measure: Change From Baseline to Week 336 in CD4 Percentage

Time: Baseline to 336 weeks

Measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24

Time: Baseline to 24 weeks

Measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48

Time: Baseline to 48 weeks

Measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 96

Time: Baseline to 96 weeks

Measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 144

Time: Baseline to 144 weeks

Measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 192

Time: Baseline to 192 weeks

Measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 240

Time: Baseline to 240 weeks

Measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288

Time: Baseline to 288 weeks

Description: No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.

Measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 336

Time: Baseline to 336 weeks

Measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24

Time: Week 24

Measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48

Time: Week 48

Measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96

Time: Week 96

Measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144

Time: Week 144

Measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192

Time: Week 192

Measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240

Time: Week 240

Measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288

Time: Week 288

Description: No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.

Measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 336

Time: Week 336

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24

Time: Week 24

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48

Time: Week 48

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96

Time: Week 96

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144

Time: Week 144

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192

Time: Week 192

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240

Time: Week 240

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288

Time: Week 288

Description: No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 336

Time: Week 336

Description: Virologic failure was defined as either nonresponse or viral rebound. Nonresponse (failure to achieve response). Response was defined as either A ≥ 0.5 log10 copies/mL decrease in HIV-1 RNA from baseline at 2 consecutive visits, or HIV-1 RNA < 400 copies/mL at 2 consecutive visits. Viral rebound was defined as either Participants who achieved a ≥ 0.5 log10 copies/mL decrease from baseline in plasma HIV-1 RNA at 2 consecutive visits, who then subsequently achieved plasma HIV-1 RNA values ≥ 1.0 log10 copies/mL above their on-study nadir (lowest value) and/or plasma HIV-1 RNA values ≥ the baseline value at 2 consecutive visits, or Participants who achieved plasma HIV-1 RNA levels of < 400 copies/mL at 2 consecutive visits, and then subsequently had plasma HIV-1 RNA levels > 1000 copies/mL at 2 consecutive visits. The virologic failure rate was estimated from Kaplan-Meier product limit method by including all HIV-1 RNA data collected during the double-blind phase.

Measure: Percentage of Participants With Virologic Failure Through Week 48

Time: Up to 48 weeks

21 A Randomized, Blinded, 12-week Comparison of Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in HIV-1 Infected, Treatment Naive Subjects. There is a 36 Week, Open Label, Extension Phase for Eligible Subjects.

Elvucitabine is a novel nucleoside analog that is being studied as a treatment for patients infected with HIV-1. This Phase II study will enroll 60 HIV-1 naive subjects to assess the efficacy and safety of elvucitabine compared to lamivudine in combination with tenofovir and efavirenz measured by changes in the patient's HIV-RNA level and CD4 cell count. The study treatment will be 12 weeks of blinded study medication followed by an additional 84 weeks of open label treatment if the patient's response to treatment meets certain endpoints. Also there will be assessment of the pharmacokinetics of elvucitabine during the study.

NCT00350272
Conditions
  1. HIV Infections
Interventions
  1. Drug: elvucitabine
  2. Drug: Lamivudine
  3. Drug: Tenofovir
  4. Drug: Efavirenz
MeSH:HIV Infections

2. Are 18 through 65 years old 3. Have documented HIV-1 infection by written prior history and clinically stable with no AIDS-defining events in the 3 months prior to Screening 4. Have plasma HIV-1 RNA levels greater than or equal to 5000 copies/mL at Screening 5. Are HIV-1 strain sensitive to elvucitabine, lamivudine, emtricitabine as demonstrated by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1 Genotyping Kit 6. Are HIV-1 strain genotypically sensitive to efavirenz (negative for K103 and Y188L mutations) and tenofovir (negative for K65R mutation) by TRUGENE HIV-1 Genotyping Kit 7. Have a CD4 count greater than or equal to 200 cells/mL and less than 500 cells/mL 8. Have acceptable hematologic and chemistry parameters, including the following: - Hemoglobin (Hgb) greater than or equal to 11g/dL - Absolute neutrophil count greater than or equal to 2000 cells/mm3 - Platelets greater than or equal to 125 000/mm3 - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 1.5 times the upper limit of normal - Total bilirubin less than or equal to 1.5 times the upper limit of normal - Creatinine within normal range 9. Are capable of understanding and has signed the informed consent document 10. --- M184V --- --- M184I --- --- D237E --- --- Y188L --- --- K65R ---

Subjects must be genotypically sensitive to efavirenz (negative for K103 or Y188L mutations) and tenofovir (negative for K65R mutation) as demonstrated by TRUGENE HIV-1 Genotyping Kit. --- Y188L --- --- K65R ---

Primary Outcomes

Description: Proportion of subjects having achieved a virologic response for elvucitabine 10 mg/day in combination with efavirenz and tenofovir in HIV-1-infected subjects over 12 weeks compared with the proportion of subjects having achieved a virologic response for lamivudine 300 mg/day in combination with efavirenz and tenofovir. Virologic response was defined as having achieved undetectable (<50 copies/mL) HIV-1 RNA levels from baseline assessment.

Measure: The Proportion of Subjects With Virologic Response for 10 mg/Day Elvucitabine in HIV-1-infected Subjects by 12 Weeks Compared With the Proportion of Subjects With Lamivudine 300 mg/Day.

Time: 12 Weeks

Description: Determination of the safety profile of elvucitabine as defined by the frequency, type and severity of treatment-emergent adverse events and the frequency of Grade 3 and Grade 4 laboratory abnormalities.

Measure: The Safety Profile of Elvucitabine.

Time: 12 Weeks

22 A Multicenter, Randomized, Double-Blind, Comparative Trial Of A Novel CCR5 Antagonist, UK-427,857, In Combination With Zidovudine/Lamivudine Versus Efavirenz In Combination With Zidovudine/Lamivudine For The Treatment Of Antiretroviral-Naive HIV-1 Infected Subjects

Maraviroc (UK-427,857), a selective and reversible CCR5 coreceptor antagonist, has been shown to be active in vitro against a wide range of clinical isolates (including those resistant to existing classes). In HIV-1 infected patients, maraviroc (UK-427,857) given as monotherapy for 10 days reduced HIV-1 viral load by up to 1.6 log, consistent with currently available agents. Safety and toleration have been studied in over 400 subjects for up to 28 days at 300 mg twice daily. No significant effects were seen on the QTc interval. The goal of this study is to compare the safety and efficacy of maraviroc (UK-427,857) versus efavirenz, when each are combined with two other antiretroviral agents, in patients who are previously naive to antiretroviral therapy. This study will involve approximately 200 centers from around the world to achieve a total randomized subject population of 1071 subjects. Patients will be randomly assigned to one of three groups: maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily), Maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily) or efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily). The study will enroll over approximately an 18 month period (5 months Phase 2b run-in, 13 months Phase 3) with 96 weeks of treatment. This may be extended for an additional 3 years depending on the results at 96 weeks. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 48 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24, 48 and 96. A computerized tomography (CT) scan will also be performed, at selected centers, at study entry and week 96. Patients will be asked to complete a symptom distress questionnaire at study entry, weeks 12, 24, 48 and 96.

NCT00098293
Conditions
  1. HIV-1
Interventions
  1. Drug: Maraviroc + Zidovudine/Lamivudine
  2. Drug: Efavirenz + Zidovudine/Lamivudine
  3. Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine

Following mutations associated with NRTIs were summarized at time of failure: Any zidovudine/lamivudine (Zid/Lam), Any thymidine analogue-associated mutation (TAM), methionine (M) to valine/isoleucine (V/I) substitution at residue (r) 184 (M184V/I), lysine (K) to arginine (R) substitution at residue 65 (K65R) and any other NRTI mutations.. Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96. --- M184V --- --- K65R ---

Primary Outcomes

Measure: Percentage of Participants With Viral Load of Less Than 400 Copies/Milliliter [Copies/mL] and Less Than 50 Copies/mL of Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) at Week 48 for Full Analysis Set (FAS) Population

Time: Week 48

Description: Percentage of participants with viral load of less than 400 copies/mL and less than 50 copies/mL of HIV-1 RNA were not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

Measure: Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 48 for Per Protocol (PP) Population

Time: Week 48

Secondary Outcomes

Measure: Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 Analyzed Using Logistic Regression

Time: Week 48

Measure: Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 Analyzed Using Logistic Regression

Time: Week 96

Description: Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.

Measure: Change From Baseline in Log 10-transformed Plasma Viral Load (HIV-1 RNA) Levels at Week 48 and 96

Time: Baseline, Week 48, Week 96

Description: TAD from baseline was calculated as area under the curve (AUC) of HIV-1 RNA load (log10 copies/mL) divided by time period minus baseline HIV-1 RNA load (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose. Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

Measure: Time-Averaged Difference (TAD) in log10-transformed HIV-1 RNA Levels

Time: Baseline up to Week 48 and Week 96

Description: Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.

Measure: Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 48 and 96

Time: Baseline, Week 48, Week 96

Description: Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose. Change from baseline in lymphocyte CD8 count at Week 48 and 96 was not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

Measure: Change From Baseline in Lymphocyte Cluster of Differentiation 8 (CD8) Count at Week 48 and 96

Time: Baseline, Week 48, Week 96

Description: Time to virologic failure based on observed HIV-1 RNA levels and failure events (death;permanent discontinuation of drug;lost to follow-up [LTFU];new anti-retroviral drug added [except background drug change to drug of same class];or on open label for early non-response or rebound). Failure:at Time 0 if level not <400 copies/mL(2 consecutive visits) before events or last available visit;at time of earliest event if level <400 copies/mL(2 consecutive visits);failure if level >=400 copies/mL(2 consecutive visits) or 1 visit >=400 copies/mL followed by permanent discontinuation of drug or LTFU.

Measure: Time to Virologic Failure

Time: Week 48, Week 96

Description: Number of participants per tropism status (C-X-C chemokine receptor 5 {CCR5} [R5], C-X-C chemokine receptor type 4 {CXCR4} [X4], Dual/mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at baseline and time of treatment failure analyzed through week 48 visit. Treatment failure: discontinuation due to insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as last on treatment assessment.

Measure: Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48

Time: Baseline, time of failure through Week 48

Description: Number of participants per tropism status (R5, X4, DM, or NR/NP) at baseline and time of treatment failure analyzed through week 96 visit. Treatment failure defined as insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as BLQ. The assessment for time of treatment failure was defined as last on treatment assessment.

Measure: Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 96

Time: Baseline, time of failure through Week 96

Description: Phenotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) assessed at screening by Monogram Bioscience PhenoSense genotype (MBPSGT) assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Phenotypic resistance to maraviroc was assumed in maraviroc treatment failures with X4-using virus and in R5 maraviroc treatment failures using Monogram Bioscience PhenoSense Entry Assay. Phenotypic resistance to zidovudine, lamivudine, efavirenz and maraviroc at time of failure was summarized.

Measure: Number of Participants With Phenotypic Resistance at Time of Treatment Failure Through Week 48 and 96

Time: Screening, time of failure through Week 48, Week 96

Description: Genotypic resistance to NRTIs was assessed by identification of relevant mutations at screening using MBPSGT assay and repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure through week 48 and week 96. Following mutations associated with NRTIs were summarized at time of failure: Any zidovudine/lamivudine (Zid/Lam), Any thymidine analogue-associated mutation (TAM), methionine (M) to valine/isoleucine (V/I) substitution at residue (r) 184 (M184V/I), lysine (K) to arginine (R) substitution at residue 65 (K65R) and any other NRTI mutations.

Measure: Number of Participants With NRTI Associated Mutations at Time of Treatment Failure Through Week 48 and 96

Time: Screening, time of failure through Week 48, Week 96

Description: Genotypic resistance: mutations at screening by MBPSGT assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Efavirenz mutation:lysine to aspargine at r103(K103N);tyrosine to cysteine/isoleucine at r181(Y181C/I);tyrosine to cysteine/leucine/histidine at r188(Y188C/L/H);glycine to alanine/serine at r190(G190A/S);valine to alanine to r106(V106A);leucine to isoleucine at r100(L100I);alanine to glycine at r98(A98G);lysine to glutamic acid at r101(K101E);valine to isoleucine at r108(V108I);proline to histidine at r225(P225H);methionine to leucine at r230(M230L).

Measure: Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96

Time: Screening, time of failure through Week 48, Week 96

Description: Association between baseline resistance and virological response was assessed as percentage of participants with HIV-1RNA levels less than 50 copies/mL by OSS at screening. OSS categorized as 0, 1, 2, >3 (maximum value of 6) and calculated as the sum of the net assessment of in-vitro phenotypic and genotypic susceptibility using a binary scoring system (0= resistant, 1= sensitive or susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.

Measure: Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL at Week 48 and Week 96 by Overall Susceptibility Score (OSS) at Screening

Time: Baseline, Week 48, Week 96

Other Outcomes

Measure: Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 96

Time: Week 96

23 Cell Cycle Independent Antiretroviral Therapy: Combination of Nevirapine, FTC, and Tenofovir

Open label, two year study of the clinical efficacy of the combination of FTC, Tenofovir, and Nevirapine. Sixty HIV infected patients without previous exposure to antiretroviral therapy will be enrolled. Study will include a pharmacokinetic substudy to evaluate the interaction of FTC and Nevirapine. Truvada may be used.

NCT00344461
Conditions
  1. HIV
Interventions
  1. Drug: Nevirapine, FTC, and Tenofovir

Evidence of mutation associated with primary drug resistance to Nevirapine (K103N, Y181C, Y188L, G190S), Tenofovir (M41L, T69 insertion, Q151M, L210W,and K65R), and/or FTC (184V) previously documented, or at time of screening. --- K103N --- --- Y181C --- --- Y188L --- --- G190S --- --- M41L --- --- Q151M --- --- L210W --- --- K65R ---

Primary Outcomes

Description: The primary outcome is sustained Virologic response, defined as HIV-1 RNA <500 copies/mL until trial completion at 96 weeks.

Measure: Number of Participants With Sustained Virologic Response

Time: 96 Weeks

Secondary Outcomes

Description: The number of participants with grades 2,3 and 4 adverse events and laboratory toxicities.

Measure: Patients With Grade 2, 3 and 4 Adverse Events and Laboratory Toxicities

Time: Protocol length is 96 weeks

Description: The number of participants with plasma HIV RNA < 50 copies/mL

Measure: Patients With Plasma HIV RNA < 50 Copies/mL

Time: 96 weeks.

Description: The number of participants with plasma HIV RNA < 400 copies/mL

Measure: Patients With Plasma HIV RNA < 400 Copies/mL

Time: 96 weeks

Description: Percent Change From Baseline in Plasma HIV RNA at 96 weeks

Measure: Change in Plasma HIV RNA From Baseline to Week 96

Time: Baseline to week 96

Description: To determine the mean change from Baseline in CD4 cell count to week 96.

Measure: Changes in CD4 Cell Count From Baseline and Week 96

Time: Baseline to week 96

24 An Open-Label, Randomized Comparison of Elvitegravir-Cobicistat-Tenofovir Alafenamide-Emtricitabine Versus Efavirenz-Tenofovir Disoproxil Fumarate-Lamivudine in Patients Starting Antiretroviral Therapy on the Day of HIV Diagnosis

Randomized, open-label study comparing Elvitegravir-Cobicistat-Tenofovir Alafenamide-Emtricitabine (Genvoya) vs. Efavirenz-Tenofovir Disoproxil Fumarate-Lamivudine (EFV-TDF-3TC) in patients starting ART on the day of HIV diagnosis.

NCT03405194
Conditions
  1. HIV/AIDS
Interventions
  1. Drug: Elvitegravir, Cobicistat, TAF, FTC
  2. Drug: Efavirenz, TDF, and 3TC
MeSH:Acquired Immunodeficiency Syndrome HIV Infections

- Clinical evidence of cirrhosis (ascites or encephalopathy); - Anticipated need for hepatitis C therapy during the study period; - Baseline CrCl <30 mL/minute by the Cockcroft-Gault equation (late exclusion, as creatinine results will not be available at the time of enrollment); - Either the K65R mutation or more than 3 thymidine analogue mutations on baseline resistance testing (late exclusions, after baseline resistance results are available). --- K65R ---

Primary Outcomes

Description: To compare the proportion of participants who are retained in care with a plasma HIV-1 RNA level <200 copies/ml

Measure: 48-week viral suppression

Time: 48 weeks after enrollment

Secondary Outcomes

Description: Proportion of participants who are retained in care with a plasma HIV-1 RNA level <200 copies/ml

Measure: 12-week viral suppression

Time: 12 weeks after enrollment

Description: Genotypic resistance to EFV and/or nucleoside reverse transcriptase inhibitors

Measure: Baseline resistance to ART medications

Time: Baseline

Description: Median change in CD4 count over the study period (baseline to 48 weeks)

Measure: Change in CD4 count

Time: 48 weeks after enrollment

Description: Proportion of patients meeting the WHO definition for ART treatment failure over the study period

Measure: Virologic failure

Time: 48 weeks after enrollment

Description: Proportion of participants with a new Division of AIDS Grade 3 or 4 adverse event or laboratory abnormality that is at least a one-grade increase from baseline

Measure: Adverse events

Time: 48 weeks after HIV testing

Description: Proportion of participants with a new Division of AIDS Grade 1 to 4 neurologic or psychiatric disorder that is at least a one-grade increase from baseline

Measure: Neurologic or psychiatric adverse event

Time: 48 weeks

Description: Mean scores on the Pittsburgh Sleep Quality Index

Measure: Sleep Quality

Time: 4, 12, 24, and 48 weeks after enrollment

Description: Mean scores on the Patient Health Questionnaires (PHQ-9) Questionnaire

Measure: Depression

Time: 4, 12, 24, and 48 weeks after enrollment

Description: Proportion of participants who discontinue any drug in the original ART regimen

Measure: Change in ART drugs

Time: 48 weeks after HIV testing after enrollment

25 Efficacy and Safety Evaluation of TDF-based Regimen in Thai HIV-infected Children

This study will assess the safety and efficacy of generic TDF from Governmental Pharmaceutical Organization (GPO) in HIV-infected children

NCT01815255
Conditions
  1. HIV-infected Thai Children
Interventions
  1. Drug: tenofovir (TDF)

Inclusion Criteria: - children who are changing to TDF due to adherence problem or treatment failure - children who are already on TDF due to their clinical indication Exclusion Criteria: - child/caretaker refuse to participate in this study - cannot adhere to the study schedule Inclusion Criteria: - children who are changing to TDF due to adherence problem or treatment failure - children who are already on TDF due to their clinical indication Exclusion Criteria: - child/caretaker refuse to participate in this study - cannot adhere to the study schedule HIV-infected Thai Children TDF is a nucleotide reverse transcriptase inhibitor (NRTI) which can be taken only once per day and continues to have good efficacy even in patients who have resistance to other NNRTI in the absence of K65R mutation. --- K65R ---

Primary Outcomes

Description: Number of patients who have viral load less than 50 copies/ml at week 48 and week 96

Measure: viral load

Time: week 48 and 96

Secondary Outcomes

Description: Number of patients with renal toxicity assessed by GFR and with proximal tubular effect

Measure: renal status

Time: weeks 24, 48, 72, and 96

Description: Agreement between self reported adherence by visual analogue scale (VAS) pill count and TDM Sensitivity and specificity of self-reported adherence and pill count against gold standards of TDM and undetectable viral load

Measure: adherence

Time: every 3 months

Description: Resistant mutations in patients who fail TDF-based regimen and response to new regimen

Measure: resistance

Time: every 3 months

Description: Proportion of patients who develop adverse events which are related to TDF and other ARVs

Measure: adverse events

Time: weeks 24, 48, 72, and 96

26 GMB: Phase IV, Multicenter, Randomized, Open-Label Pilot Study of Truvada (TDF+FTC) or Emtricitabine (FTC) Alone Versus HAART Interruption in HIV-Infected Patients Who Need to Interrupt HAART and Who Are Infected With HIV Isolates Containing at Least 2 TAMs (or K65R) and M184V

Many patients who already harbor drug-resistant HIV require interruption of HAART due to poor compliance, poor quality of life, toxicity or development of resistance. In these patients interruption of HAART has a negative impact on patient immune status due to the reemergence of wild-type virus which is in general more pathogenic than HIV isolates containing resistance mutations. There is a need for "bridging" antiretroviral regimens that might prolong time off conventional HAART whilst waiting for a new regimen that is either fully suppressive or less toxic or less demanding for the patient.

NCT00362687
Conditions
  1. HIV Infections
Interventions
  1. Drug: Truvada (TDF+FTC) alone
  2. Drug: FTC alone
  3. Procedure: No HAART
MeSH:HIV Infections

GMB: Phase IV, Multicenter, Randomized, Open-Label Pilot Study of Truvada (TDF+FTC) or Emtricitabine (FTC) Alone Versus HAART Interruption in HIV-Infected Patients Who Need to Interrupt HAART and Who Are Infected With HIV Isolates Containing at Least 2 TAMs (or K65R) and M184V. --- K65R ---

- Available genotype (current or historical) showing M184V and (≥ 2 TAMs or K65R). --- M184V --- --- K65R ---

Primary Outcomes

Measure: To compare CD4 cell loses 24 weeks after HAART discontinuation

Time: Through 48 weeks

Secondary Outcomes

Measure: Proportion of patients with re-initiation of HAART within 24 and 48 weeks

Time: Through 48 weeks

Measure: To compare CD4 cell loses 48 weeks after HAART discontinuation

Time: Through 48 weeks

Measure: To compare HIV viral loads 4, 24 and 48 weeks after HAART discontinuation:time-weighted average change from baseline through 24 and 48 weeks (DAVG24 and DAVG48) for log10 plasma HIV-1 RNA for patients with plasma HIV-1 RNA >50 copies/mL at baseline

Time: Through 48 weeks

Measure: To compare HIV viral loads 4, 24 and 48 weeks after HAART discontinuation: time-weighted average change from 4 weeks through 24 and 48 weeks (DAVG24 and DAVG48) for log10 plasma HIV-1 RNA for patients with <50 copies/mL at baseline

Time: Through 48 weeks

Measure: To compare HIV viral loads 4, 24 and 48 weeks after HAART discontinuation: proportion of patients with HIV RNA <400 and <50 copies/mL at 4 weeks for subjects with plasma HIV-1 RNA <50 copies/mL at baseline

Time: Through 48 weeks

Measure: To compare HIV viral loads 4, 24 and 48 weeks after HAART discontinuation: compare log10 plasma HIV-1 RNA at week 4 for patients with HIV-RNA < 50 copies/mL at baseline.

Time: Through 48 weeks

Measure: To compare development of new mutations in the reverse transcriptase gene 24 and 48 weeks after HAART discontinuation.

Time: Through 48 weeks

Measure: Proportion of patients with any adverse event.

Time: Through 48 weeks

Measure: Proportion of patients for each adverse event.

Time: Through 48 weeks

Measure: Distribution of the intensity if each adverse event (the greatest intensity for each adverse event within a patient will be considered).

Time: Through 48 weeks

Measure: Distribution of the relationship between the adverse effect and the study drug (the strongest relation with the study drug for each adverse event within each patient will be considered).

Time: Through 48 weeks

Measure: Proportion of patients who discontinue the study prematurely (before week 48)due to adverse events.

Time: Through 48 weeks

Measure: Changes in patient's quality of life analyses.

Time: Through 48 weeks

27 A Phase 1b, Open-label Study to Evaluate the PK, Safety and Efficacy of B/F/TAF in HIV-1 Infected, Virologically Suppressed, Pregnant Women in Their Second and Third Trimesters

The primary objective of this study is to evaluate the steady state pharmacokinetics of bictegravir (BIC) and confirm the dose of BIC/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in HIV-1 infected, virologically suppressed pregnant women in their second and third trimesters.

NCT03960645
Conditions
  1. HIV-1-infection
Interventions
  1. Drug: B/F/TAF

Key Inclusion Criteria: - The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures - With singleton pregnancy, at least 12 weeks but not more than 31 weeks pregnant at the time of screening - Agree not to breastfeed for the duration of the study - Currently on a stable antiretroviral regimen for ≥ 6 months preceding the screening visit - Documented plasma HIV-1 RNA levels of < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at the screening visit - Have no documented or suspected resistance to FTC, Tenofovir (TFV), or integrase strand-transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R or M184V/I - Historic genotype reports will be collected if available - Have a normal ultrasound, completed locally prior to the Day 1 visit, with no evidence of any fetal malformation or structural abnormality affecting either fetus or placenta - Normal maternal alfa-fetoprotein level at the screening visit Key Exclusion Criteria: - Have chronic hepatitis B virus (HBV) - Have active hepatitis C virus (HCV) infection - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening Note: Other protocol defined Inclusion/Exclusion criteria may apply. --- K65R ---

Primary Outcomes

Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Measure: Pharmacokinetic (PK) Parameter: AUCtau of BIC

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Secondary Outcomes

Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Measure: PK Parameter: AUCtau of emtricitabine (FTC) and tenofovir alafenamide (TAF)

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Description: AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Measure: PK Parameter: AUClast of BIC, FTC, and TAF

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Description: Cmax is defined as the maximum observed concentration of drug during the dosing interval.

Measure: PK Parameter: Cmax of BIC, FTC, and TAF

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Description: Ctau is defined as the observed drug concentration at the end of the dosing interval.

Measure: PK Parameter: Ctau of BIC and FTC

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Description: Clast is defined as the last observable concentration of drug.

Measure: PK Parameter: Clast of BIC, FTC, and TAF

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Description: Tmax is defined as the time (observed time point) of Cmax.

Measure: PK Parameter: Tmax of BIC, FTC, and TAF

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Description: t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Measure: PK Parameter: t1/2 of BIC, FTC, and TAF

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Description: CL/F is defined as the apparent oral clearance following administration of the drug.

Measure: PK Parameter: CL/F of BIC, FTC, and TAF

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Description: Vz/F is defined as the apparent volume of distribution of the drug.

Measure: PK Parameter: Vz/F of BIC, FTC, and TAF

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Description: λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.

Measure: PK Parameter: λz of BIC, FTC, and TAF

Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Measure: Proportion of Participants With HIV-1 RNA < 50 Copies/mL Using the Missing = Excluded Approach

Time: At the Time of Delivery

28 A Randomized, Open-Label Study Assessing Safety, Tolerability and Efficacy of an Induction-Maintenance Treatment Strategy Including Lopinavir/Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine Versus Efavirenz Plus Tenofovir Disoproxil Fumarate and Emtricitabine in Antiviral-naïve HIV-1/HCV Co-Infected Subjects

The purpose of this study is to determine whether a simplified lopinavir/ritonavir-based therapy will continue to keep the viral load at very low levels after initial treatment with a combination of Kaletra (lopinavir/ritonavir) plus tenofovir and emtricitabine.

NCT00121017
Conditions
  1. HIV Infection
  2. Hepatitis C
Interventions
  1. Drug: Kaletra (lopinavir/ritonavir)
  2. Drug: Sustiva (efavirenz)
  3. Drug: Truvada (emtricitabine/tenofovir disoproxil fumarate)
MeSH:Hepatitis C

- The screening HIV-1 genotype resistance report suggests resistance or possible resistance to the study RTI(s) or lopinavir/ritonavir; Evidence of possible resistance to efavirenz; Presence of one of the following mutations: RT L1001, K103N, V106A or M, V108I, Y181C or I, Y188L, G190A or S, P225H, M230L; Evidence of possible resistance to emtricitabine or lamivudine; Presence of one of the following mutations: RTm184V or I; Evidence of possible resistance to tenofovir; Presence of RT K65R or insertion at codon 69, or Presence of 2 or more of the following mutations: RTm41L, D67N, K70R, L210W; any change at T215, K219Q or evidence of possible resistance to lopinavir/ritonavir; Presence of one or more of the following mutations: protease I47V or A, G48V, I50V, V82A or F or T or S, I84V, 190M or Presence of 3 or more of the following mutations: protease L10F or I or R or V, K20M or R, L24I, V32I, L33F, M36I, M46I or L, F53L; any change at I54, A71V or T, G73S. --- K103N --- --- V106A --- --- V108I --- --- Y181C --- --- Y188L --- --- G190A --- --- P225H --- --- M230L --- --- K65R ---

Primary Outcomes

Measure: The proportion of subjects with a plasma HIV-1 RNA level below 50 copies/mL at Week 96.

Secondary Outcomes

Measure: Vital signs

Measure: Physical examinations

Measure: Clinical laboratory tests

29 A Phase IIa, Randomized, Double-blind, Active-controlled, 12-week Study of Amdoxovir (Two Doses) Versus Tenofovir DF, in Combination With Zidovudine in HIV-1 Treatment-experienced Subjects With M184I/V Mutation in Addition to 0-2 Confirmed Thymidine Analog Mutations.

This is a double-blind Phase 2a study to test the safety and efficacy of an investigational HIV drug, amdoxovir (300 mg or 500 mg twice daily) compared with tenofovir DF 300 mg once daily in HIV-1 infected antiretroviral therapy-experienced subjects who are currently failing antiretroviral therapy. There are three treatment groups (N=45). Subjects will be randomized to receive either amdoxovir 300 mg twice daily (n=15) or amdoxovir 500 mg twice daily (n=15) or tenofovir DF 300 mg once daily (n=15); each in combination with zidovudine 300 mg twice daily. The study will assess initially amdoxovir (300 mg or 500 mg twice daily) or tenofovir DF 300 mg once daily, both in combination zidovudine 300 mg twice daily plus failing third drug, but then with lopinavir/ritonavir (400 mg/100 mg twice daily) after Week 2. Subjects who received amdoxovir (300 mg or 500 mg twice daily) and benefited from the drug may choose to enroll in the 36-week open-label study.

NCT01737359
Conditions
  1. Human Immunodeficiency Virus Infection
Interventions
  1. Drug: amdoxovir 300 mg bid
  2. Drug: amdoxovir 500 mg bid
  3. Drug: tenofovir DF 300 mg qd
MeSH:Acquired Immunodeficiency Syndrome HIV Infections

- Genotypic resistance testing at screening indicating K65R, L74V, Q151M mutation. --- K65R ---

Primary Outcomes

Measure: HIV-1 viral load

Time: change from baseline to Week 2

Measure: Safety and Tolerability- Incidence of adverse events and laboratory abnormalities

Time: number and frequency from baseline through Week 12

Secondary Outcomes

Measure: HIV-1 viral load

Time: change from baseline to Weeks 4, 8 and 12

Measure: Changes in Immunologic Function (CD4 cell counts)

Time: changes from baseline to Weeks 4, 8 and 12

30 A Phase II, Open Label, Single Arm Study of the 48-Week Virologic and Immunologic Response to Lopinavir/Ritonavir (Kaletra) as a Single Agent in a Cohort of HIV Positive Adult Patients

Expected Enrollment: 40 patients Study Start Date: June 2005 Study Objectives: - To conduct a pilot study to assess the safety, tolerability, and antiviral activity of Kaletra 400/100 mg taken twice a day (bid) in antiretroviral (ARV)-naïve HIV-infected patients at Week 48 Primary Objectives: - To determine the proportion of patients with HIV RNA <400 copies/mL at weeks 24 and 48 - To determine the proportion of patients with HIV RNA < 50 at weeks 24 and 48 - To elucidate the specific adverse event (AE) profile of Kaletra single agent therapy Secondary Objectives: - To assess the proportion of patients below the limit of quantification (LOQ) at each visit. Patients will be observed at baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48. - To determine the time to HIV RNA reaching <400 and <50 copies/mL - To determine the time to virologic failure - To assess change from baseline at each visit for HIV RNA and CD4 count at weeks 4, 8, 12, 24 and 48. - To assess changes in genotype from baseline to time of confirmed virologic failure (2 consecutive HIV RNA measurements >400 copies/mL after suppressing to <400 copies/mL) or at time of treatment intensification. - To characterize changes in lipid and triglyceride concentrations over time and the effect of treatment with appropriate drugs (fibrate or statin, if necessary) on these elevations. - To evaluate the safety and tolerability of subjects through 48 weeks of drug exposure. - To describe virologic response following intensification in Kaletra single agent virologic failures

NCT00116636
Conditions
  1. HIV Infections
Interventions
  1. Drug: Kaletra
MeSH:HIV Infections HIV Seropositivity

- Patient has an M184V mutation in reverse transcriptase, or mutations at 10, 20, 32, 46, 47, 48, 50, 54, 71, 73, 82, 84, or 90; - K65R mutation or 2 or more TAMs at baseline - History of active substance abuse, excluding cannabis, or psychiatric illness that, in the opinion of the investigator, would preclude compliance with protocol, dosing schedule and assessments. --- M184V --- --- K65R ---

Primary Outcomes

Measure: Proportion of patients with plasma HIV-1 RNA <400 copies/mL at Week 24 and 48

Measure: Proportion of patients with plasma HIV-1 RNA < 50 copies/mL at Week 48

Secondary Outcomes

Measure: Proportion of patients with plasma HIV-1 RNA <400 copies/mL or <50 copies/mL at each study visit

Measure: Proportion of patients with plasma HIV-1 RNA <50 copies/mL at Weeks 24 and 48 Weeks

Measure: Number of weeks until HIV RNA <400 copies/mL and <50 copies/mL, respectively

Measure: Change from baseline to each study visit in plasma HIV-1 RNA and CD4+ cell count

Measure: Time-averaged change from baseline to Weeks 12, 24 and 48 (AUCMB) in plasma HIV-1 RNA and CD4+cell count

Measure: Change in HIV genotype and phenotype in patients who either intensify study therapy or experience virologic rebound

Measure: HIV genomic sequence in treatment failures

Measure: Adverse events and treatment-limiting toxicities at all time points

Measure: Baseline and on-therapy assessment of clinical laboratory parameters

Measure: Change from baseline over time in clinical laboratory parameters including fasted triglycerides, total cholesterol, direct HDL cholesterol and LDL cholesterol

31 A Phase 4, Single-Arm Study to Evaluate the Safety, Antiviral Activity and Pharmacokinetics of Tenofovir Disoproxil Fumarate in Combination With Emtricitabine in HIV-1 Infected Patients Experiencing Various Degrees of Renal Impairment

The purpose of this study is to provide long-term clinical safety and efficacy data for tenofovir disoproxil fumarate and emtricitabine in HIV-infected patients experiencing various degrees of renal impairment.

NCT00106379
Conditions
  1. HIV Infections
Interventions
  1. Drug: Truvada (tenofovir DF + emtricitabine)
  2. Drug: Emtriva (emtricitabine)
  3. Drug: Viread (tenofovir DF)
MeSH:HIV Infections

- Women of childbearing potential who are unwilling to use an effective contraceptive method during the study - Contraindications to tenofovir DF, emtricitabine or efavirenz - Undergoing treatment for tuberculosis - Using atazanavir - Prior history of mutation M184V, K65R or T69 insertion - Z-score on pre-baseline DEXA scan less than -2.5 - The following laboratory values within 30 days prior to study entry: *absolute neutrophil count (ANC) less than 750/mm3, *hemoglobin less than 9.0 g/dL, *platelet count less than 50,000/mm3, *AST (SGOT) or ALT (SGPT) less than 5 x ULN and *CD4 cell count less than 100/mm3. --- M184V --- --- K65R ---

Primary Outcomes

Measure: HIV-1 infection

Secondary Outcomes

Measure: HIV-1 infection in renally impaired HIV infected patients

32 AntiRetroviral Therapy In Second-line: Investigating Tenofovir-lamivudine-dolutegravir (ARTIST): a Randomised Controlled Trial

The strategy to support virological suppression on second-line antiretroviral treatment (ART) includes the provision of ART that has a low pill burden, good tolerability, low toxicity, is easily monitored, has a high barrier to resistance, and that is low cost. The fixed-dose combination of tenofovir-lamivudine-dolutegravir offers significant advantage as a potential second-line regimen compared to the World Health Organization standard of care second-line regimen of zidovudine-lamivudine-dolutegravir, in terms of cost, tolerability and monitoring requirements. The ARTIST study is a phase 2, randomised, double-blind, placebo-controlled trial aiming to determine the proportion of patients achieving virological suppression when recycling the tenofovir-emtricitabine/lamivudine backbone with dolutegravir (tenofovir-lamivudine-dolutegravir fixed-dose combination) as a second-line with and without a lead-in supplementary dose of dolutegravir, in patients failing a tenofovir-emtricitabine/lamivudine-efavirenz first-line regimen. There is evidence to suggest that even in the presence of resistance mutations to tenofovir and lamivudine (K65R or M184V/I), using this backbone with dolutegravir will provide an effective second-line regimen in patients who have failed a first-line regimen of tenofovir-emtricitabine/lamivudine-efavirenz. The strategy of giving a lead-in supplementary dose of dolutegravir is in view of the inducing effect of efavirenz on dolutegravir metabolism and transport that persists for 2 weeks after efavirenz is stopped; the inducing effect decreases with time after efavirenz is stopped. Given that these patients will have elevated viral loads, a high baseline risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance and efavirenz resistance, and the inducing effect of efavirenz on dolutegravir metabolism and transport that persists for 2 weeks, this study will comprise two stages. The first stage will evaluate virological suppression in 62 participants initiated on the fixed-dose combination of tenofovir-lamivudine-dolutegravir with a lead-in supplementary dose of dolutegravir for the first 14 days. The study will progress to the second stage if this strategy proves effective, and 130 participants will then be randomised to receive the fixed-dose combination of tenofovir-lamivudine-dolutegravir with and without this lead-in dose. The primary endpoint is virological suppression (viral load <50 copies/mL) at 24 weeks. A pharmacokinetic sub-study will be conducted on 12 participants in stage 1 and 24 participants in stage 2, to assess the trough concentrations of dolutegravir and off-treatment concentrations of efavirenz at day 3, 7, 14, and 28. This is to evaluate the need for the lead-in supplementary dose of dolutegravir.

NCT03991013
Conditions
  1. HIV Infections
Interventions
  1. Drug: Dolutegravir 50 mg
  2. Drug: Placebo
MeSH:HIV Infections

There is evidence to suggest that even in the presence of resistance mutations to tenofovir and lamivudine (K65R or M184V/I), using this backbone with dolutegravir will provide an effective second-line regimen in patients who have failed a first-line regimen of tenofovir-emtricitabine/lamivudine-efavirenz. --- K65R ---

Primary Outcomes

Description: Proportion of participants with HIV viral load <50 copies/mL at 24 weeks analysed by modified intention to treat (ITT) and according to the FDA snapshot algorithm, overall and stratified by the presence or absence of resistance to tenofovir and lamivudine at baseline.

Measure: Virological suppression at 24 weeks

Time: 24 weeks

Secondary Outcomes

Description: To describe resistance profile at baseline (NRTI and efavirenz resistance), and treatment-emergent resistance to integrase inhibitor and NRTI in participants who experience virological failure.

Measure: Antiretroviral resistance mutations by genotypic resistance testing

Time: Baseline, 24 and 48 weeks

Description: To evaluate the trough concentrations (ng/mL) of dolutegravir and the residual concentrations (ng/mL) of efavirenz in the period after switching regimens. To evaluate the proportion of participants with dolutegravir trough concentrations above the protein-adjusted 90% inhibitory concentration (PA-IC90) value at all pharmacokinetics time points.

Measure: Residual efavirenz concentrations and dolutegravir trough concentrations

Time: First 28 days

Description: Proportion of participants with HIV viral load <50 copies/mL at 12 and 48 weeks analysed by modified ITT.

Measure: Virological suppression at 12 and 48 weeks (modified ITT)

Time: 12 and 48 weeks

Description: Proportion of participants with HIV viral load <50 copies/mL at 12, 24 and 48 weeks analysed per protocol.

Measure: Virological suppression at 12, 24 and 48 weeks (per protocol)

Time: 12, 24 and 48 weeks

Description: To describe tenofovir-diphosphate concentration (ng/mL) in participants who experience virological failure and matched controls from among those who are suppressed at 24 and 48 weeks.

Measure: Adherence to treatment

Time: 24 and 48 weeks

Description: Change in CD4 count from screening at week 24 and 48.

Measure: CD4 change at 24 and 48 weeks

Time: 24 and 48 weeks

Description: To describe grade 3 and 4 drug-related adverse events, serious adverse events, and any adverse event requiring discontinuation of any drug in the ART regimen.

Measure: Adverse events

Time: 48 weeks

Description: To describe all-cause mortality.

Measure: All-cause mortality

Time: 48 weeks

33 A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching From a Regimen of Two Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) Plus a Third Agent to a Fixed Dose Combination (FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), in Virologically-Suppressed, HIV-1 Infected African American Participants

The primary objective of this study is to evaluate the efficacy of switching from a regimen of 2 nucleos(t)Ide reverse transcriptase inhibitors (NRTIs) and a third agent to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing their baseline regimen in HIV-1 infected, virologically suppressed african american participants.

NCT03631732
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: B/F/TAF
  2. Drug: NRTIs
  3. Drug: Third Agent

By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.. Key Inclusion Criteria: - Self-describes as Black, African American, or mixed race, including Black - Currently receiving an antiretrovirals (ARV) regimen other than FDC of B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months - Allowed 3rd agents include any FDA-approved INSTI, with the exception of bictegravir, any FDA-approved NNRTI with the exception of etravirine, protease inhibitors or the CCR5 antagonist, maraviroc - If the baseline 3rd agent is dolutegravir, dosing other than 50 mg once daily is excluded - Baseline regimens containing investigational drugs or > 2 classes of ARVs are not permitted, with the exception of the pharmacologic enhancers cobicistat (taken with elvitegravir or a PI), or ritonavir (taken with a PI) - Have no documented or suspected resistance to INSTIs and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving <50 copies/mL while on an INSTI-containing regimen) - History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT substitutions are allowed, with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT will be excluded - Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen for a minimum period of 6 months and at least the last two HIV-1 RNA measurements prior to the Screening visit - HIV-1 RNA levels < 50 copies/mL at Screening - Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance Key Exclusion Criteria: - History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R),T69-insertions, or K65R/E/N in RT - No desire to switch from current ARVs - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening - Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding) - Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) - Malignancy within 5 years of screening other than cutaneous Kaposi's sarcoma, completely resected non -melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus (AIN 3). --- M184V --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215F --- --- K219Q --- --- K65R ---

By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.. Key Inclusion Criteria: - Self-describes as Black, African American, or mixed race, including Black - Currently receiving an antiretrovirals (ARV) regimen other than FDC of B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months - Allowed 3rd agents include any FDA-approved INSTI, with the exception of bictegravir, any FDA-approved NNRTI with the exception of etravirine, protease inhibitors or the CCR5 antagonist, maraviroc - If the baseline 3rd agent is dolutegravir, dosing other than 50 mg once daily is excluded - Baseline regimens containing investigational drugs or > 2 classes of ARVs are not permitted, with the exception of the pharmacologic enhancers cobicistat (taken with elvitegravir or a PI), or ritonavir (taken with a PI) - Have no documented or suspected resistance to INSTIs and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving <50 copies/mL while on an INSTI-containing regimen) - History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT substitutions are allowed, with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT will be excluded - Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen for a minimum period of 6 months and at least the last two HIV-1 RNA measurements prior to the Screening visit - HIV-1 RNA levels < 50 copies/mL at Screening - Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance Key Exclusion Criteria: - History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R),T69-insertions, or K65R/E/N in RT - No desire to switch from current ARVs - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening - Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding) - Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) - Malignancy within 5 years of screening other than cutaneous Kaposi's sarcoma, completely resected non -melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus (AIN 3). --- M184V --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215F --- --- K219Q --- --- K65R --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215F --- --- K219Q --- --- K65R ---

Key Inclusion Criteria: - Self-describes as Black, African American, or mixed race, including Black - Currently receiving an antiretrovirals (ARV) regimen other than FDC of B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months - Allowed 3rd agents include any FDA-approved INSTI, with the exception of bictegravir, any FDA-approved NNRTI with the exception of etravirine, protease inhibitors or the CCR5 antagonist, maraviroc - If the baseline 3rd agent is dolutegravir, dosing other than 50 mg once daily is excluded - Baseline regimens containing investigational drugs or > 2 classes of ARVs are not permitted, with the exception of the pharmacologic enhancers cobicistat (taken with elvitegravir or a PI), or ritonavir (taken with a PI) - Have no documented or suspected resistance to INSTIs and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving <50 copies/mL while on an INSTI-containing regimen) - History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT substitutions are allowed, with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT will be excluded - Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen for a minimum period of 6 months and at least the last two HIV-1 RNA measurements prior to the Screening visit - HIV-1 RNA levels < 50 copies/mL at Screening - Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance Key Exclusion Criteria: - History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R),T69-insertions, or K65R/E/N in RT - No desire to switch from current ARVs - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening - Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding) - Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) - Malignancy within 5 years of screening other than cutaneous Kaposi's sarcoma, completely resected non -melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus (AIN 3). --- M184V --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215F --- --- K219Q --- --- K65R ---

Key Inclusion Criteria: - Self-describes as Black, African American, or mixed race, including Black - Currently receiving an antiretrovirals (ARV) regimen other than FDC of B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months - Allowed 3rd agents include any FDA-approved INSTI, with the exception of bictegravir, any FDA-approved NNRTI with the exception of etravirine, protease inhibitors or the CCR5 antagonist, maraviroc - If the baseline 3rd agent is dolutegravir, dosing other than 50 mg once daily is excluded - Baseline regimens containing investigational drugs or > 2 classes of ARVs are not permitted, with the exception of the pharmacologic enhancers cobicistat (taken with elvitegravir or a PI), or ritonavir (taken with a PI) - Have no documented or suspected resistance to INSTIs and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving <50 copies/mL while on an INSTI-containing regimen) - History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT substitutions are allowed, with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT will be excluded - Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen for a minimum period of 6 months and at least the last two HIV-1 RNA measurements prior to the Screening visit - HIV-1 RNA levels < 50 copies/mL at Screening - Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance Key Exclusion Criteria: - History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R),T69-insertions, or K65R/E/N in RT - No desire to switch from current ARVs - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening - Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding) - Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) - Malignancy within 5 years of screening other than cutaneous Kaposi's sarcoma, completely resected non -melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus (AIN 3). --- M184V --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215F --- --- K219Q --- --- K65R --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215F --- --- K219Q --- --- K65R ---

Primary Outcomes

Description: The percentage of participants who had HIV-1 RNA ≥ 50 copies/mL at Week 24 were analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants Who Had HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set

Time: Week 24

Secondary Outcomes

Description: The percentage of participants who had HIV-1 RNA ≥ 50 copies/mL at Week 48 were analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.

Measure: Percentage of Participants Who Had HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set

Time: Week 48

Description: The percentage of participants who had HIV-1 RNA < 50 copies/mL at Week 24 were analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set

Time: Week 24

Description: The percentage of participants who had HIV-1 RNA < 50 copies/mL at Week 24 were analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Week 24 Per Protocol Analysis Set

Time: Week 24

Description: The percentage of participants who had HIV-1 RNA < 50 copies/mL at Week 48 were analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.

Measure: Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set

Time: Week 48

Description: The analysis includes values up to 1 day after permanent discontinuation of study treatment.

Measure: Change From Baseline in CD4+ Cell Count at Week 24: Full Analysis Set

Time: Baseline to Week 24

Description: The analysis includes values up to 1 day after permanent discontinuation of study treatment.

Measure: Change From Baseline in CD4+ Cell Count at Week 24: Week 24 Per Protocol Analysis Set

Time: Baseline to Week 24

Description: The analysis includes values up to 1 day after permanent discontinuation of study treatment. By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.

Measure: Change From Baseline in CD4+ Cell Count at Week 48: Full Analysis Set

Time: Baseline to Week 48

34 An Open Label Randomized Clinical Trial, to Evaluate the Treatment With Darunavir/Ritonavir + Lamivudine Once Daily Versus Continuing With Darunavir/Ritonavir Once Daily + Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV Infected Subject With Suppressed Plasma Viremia

This is an open label randomized clinial trial to evaluate the treatment with darunavir/ritonavir (800mg/100mg) plus lamivudine (300 mg) once daily versus continuing with darunavir/ritonavir (800mg/100mg) once daily plus tenofovir/emtricitabine (300mg/200mg) or abacavir/lamivudine (600mg/300mg) in HIV infected subject with suppressed plasma viremia.

NCT02159599
Conditions
  1. HIV Infection
Interventions
  1. Drug: Darunavir/Ritonavir
  2. Drug: Lamivudine
  3. Drug: Emtricitabine/tenofovir or abacavir/lamivudine
MeSH:HIV Infections

3. Treatment with darunavir/ritonavir once a day and tenofovir/emtricitabine or abacavir/lamivudine during at least 4 weeks at the moment of the screening 4. Plasma HIV RNA levels below 50 copies / ml for at least 6 months (two separate measurements at least 6 months with viremia <50 copies / ml between both). 5. HbsAg negative Exclusion Criteria: 1. Pregnant or breastfeeding woman 2. Evidence of Lamivudine resistance (any previous genotype with mutation M184V/I or K65R) and/or to darunavir (population genotype show any of the following mutations: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, T74P, L76V, I84V, L89V). --- M184V --- --- K65R ---

Primary Outcomes

Description: Undetectable viral load <50 copies/ml according to the FDA snapshot algorithm

Measure: Proportion of patients with undetectable viral load

Time: week 48

Secondary Outcomes

Description: Undetectable viral load < 50 copies/ml according to the FDA snapshot algorithm

Measure: Proportion of patients with undetectable viral load

Time: Week 24

Description: Proportion of patients with viral load < 200 copies/ml according to FDA snapshot algorithm

Measure: Proportion of patients with viral load < 200 copies/ml

Time: week 48

Description: Viral load ≥ 50 copies/ml

Measure: Proportion of patients who present viral load ≥ 50 copies /ml one time

Time: From basal visit until week 48 visit

Description: Viral load ≥ 50 copies /ml

Measure: Proportion of patients who present viral load ≥ 50 copies /ml more tan two times

Time: From basal visit until week 48 visit

Description: Viral load < 50 copies/ml

Measure: Proportion of patients who maintained viral load < 50 copies/ml in all determinations

Time: week 48

Description: CD4/µl

Measure: Median of change cells CD4/µl count from basal to week 48

Time: week 48

Measure: Median of change in triglycerides , LDL-cholesterol, HDL-cholesterol and total cholesterol from basal to week 48

Time: week 48

Description: Change in glomerular filtration

Measure: Change in renal function

Time: week 48

Measure: Change in proportion of patients with renal tubular dysfunction

Time: week 48

Other Outcomes

Description: Mutations in patients viral failure

Measure: Proportion of genotypic resistance mutations

Time: Week 48

Measure: Change in proportion of genotypic resistance mutations

Time: week 48

35 Explorations Into the Mechanism for INSTI-associated Weight Gain: a Focus on Energy Balance

Weight gain following antiretroviral therapy (ART) initiation occurs with all modern regimens. Recent real-world reports suggest that integrase strand transfer inhibitor (INSTI)-based ART may be associated with excess weight gain compared to other regimens. Weight gain appears to occur regardless of baseline weight, and is most pronounced among women and minorities, often those at highest risk of obesity-associated comorbidities. INSTI- and TAF-based regimens are now preferred regimens for most persons according to the Department of Health and Human Services ART-Treatment Guidelines. As a result, there is an urgent need to understand the underlying mechanisms for this weight gain. This study aims to understand the changes in energy balance that occur with changes in ART. Participants with HIV who have experienced >10% weight gain on INSTI (bictegravir or dolutegravir-based therapy) will be switched to doravirine for 12 weeks, and then back to their prior INSTI regimen, allowing for assessment of changes in metabolic parameters with drug withdrawal and reintroduction (with no change to NRTI-backbone). Twenty-four hour energy balance will be measured on both regimens during a 24-hour stay using a whole room indirect calorimetry, with a standardized diet. Ultimately, the investigator's goal is to understand the mechanisms of weight gain so that future interventions can most effectively mitigate ART-associated weight changes.

NCT04495348
Conditions
  1. HIV-1-infection
  2. Weight Gain
Interventions
  1. Drug: Doravirine
MeSH:Body Weight Weight Gain
HPO:Increased body weight

- Severe claustrophobia that would limit ability of participant to remain in the whole room calorimeter - Known resistance to any component of the study drugs, including detection of any of the following resistance mutations on prior HIV genotype test (genotype testing not required if not available): Doravirine resistance: V106A, V106I, V106T, V106M, Y188C, Y188H, Y188L, G190E, P225H, F227C, F227L, F227R, M230L, L234I Resistance to NRTIs: K65R, K65E, K65N, T69S (insertion complex), K70E, L74V, Y115F, Q151M, M184I, M184V. --- V106A --- --- V106I --- --- V106T --- --- V106M --- --- Y188C --- --- Y188H --- --- Y188L --- --- G190E --- --- P225H --- --- F227C --- --- F227L --- --- F227R --- --- M230L --- --- L234I --- --- K65R ---

Primary Outcomes

Description: Change in total energy expenditure (kcal/day)

Measure: Change in energy balance

Time: 24 weeks

36 A Phase 2b/3 Double Blind Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), For Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and Transgender Women Who Have Sex With Men

This study will evaluate the safety and efficacy of the injectable drug cabotegravir (CAB LA), for pre-exposure prophylaxis (PrEP) in HIV-uninfected cisgender men and transgender women who have sex with men (MSM and TGW).

NCT02720094
Conditions
  1. HIV Infections
Interventions
  1. Drug: Cabotegravir tablets
  2. Drug: TDF/FTC tablets
  3. Drug: TDF/FTC placebo tablets
  4. Drug: CAB placebo tablets
  5. Drug: CAB LA
  6. Drug: Placebo for CAB LA
MeSH:HIV Infections

Incidence of resistance mutations to study products (including but not limited to K65R, M184V/I, Q148R) among seroconverters. --- K65R ---

Primary Outcomes

Measure: Number of documented incident HIV infections in Steps 1 and 2

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Number of Grade 2 or higher clinical and laboratory adverse events

Time: Measured through participant's last study visit, up to 4 years after study entry

Secondary Outcomes

Measure: Number of documented incident HIV infections in Step 2

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Number of documented incident HIV infections in Steps 1, 2, and 3

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Number of documented incident HIV infections in Step 3

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Number of documented incident HIV infections in Step 2 and 3

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Changes from baseline in creatinine and creatinine clearance levels

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: (laboratory assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBili, creatine phosphokinase (CPK), or clinical assessment of jaundice/icterus).

Measure: Number of Grade 3 or 4 liver-related adverse events (AEs)

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Changes in Z-score from baseline and DXA criteria for osteopenia and osteoporosis

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Incidence of resistance mutations to study products (including but not limited to K65R, M184V/I, Q148R) among seroconverters

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on physical examination

Measure: Changes in weight from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on physical examination

Measure: Changes in blood pressure from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on physical examination

Measure: Changes in pulse rate from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on laboratory evaluations

Measure: Changes in fasting glucose levels from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on laboratory evaluations

Measure: Changes in fasting lipid profile from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

37 A Phase II, Open-Label, Multicentre, Randomised, Comparator Study of Substitution With Tenofovir or Abacavir in HIV-1 Infected Individuals, With a Viral Load < 50 Copies/mL, Receiving a Thymidine Analogue (Zidovudine or Stavudine) as Part of Their Highly Active Antiretroviral Therapy (HAART)

A previous study substituting zidovudine or stavudine to abacavir in patients with severe or moderate lipoatrophy has shown an increase in limb fat by DEXA. This study was conducted over a 24-week period and although improved outcomes were documented by objective measures, DEXA scans, subjective observation did not correspond. Longer-term follow up of these patients is required. This 48 week study is designed to compare the substitution of the thymidine analogues zidovudine (ZDV) or stavudine (D4T) with either tenofovir DF or abacavir, in patients treated with highly active antiretroviral therapy (HAART), and show improved outcomes on total limb fat mass, improved body shape by dual energy x-ray absorptiometry (DEXA) and computed tomography (CT) scans and improved cholesterol and triglycerides.

NCT00647946
Conditions
  1. Lipodystrophy
Interventions
  1. Drug: tenofovir DF
  2. Drug: abacavir 300mg twice daily
MeSH:Lipodystrophy
HPO:Lipodystrophy

Women of childbearing potential must agree to use a barrier method of contraception - Female subjects must not be pregnant or lactating - Subjects who in the opinion of the investigator have the ability to understand and provided written informed consent to participate in the trial - Subjects who in the opinion of the investigator have clinical lipoatrophy at > 1 body/facial site - Subjects currently receiving nucleoside analogue regimen including stavudine (d4T) or zidovudine (ZDV) - Subjects who are stable on current therapy for >16 weeks - Subjects with no prior exposure to tenofovir, abacavir, or adefovir - Subjects with no known K65R, 69S mutations or 3 or more thymidine analogue mutations - Subjects with documented viral load <50 copies/ml on 2 consecutive occasions including most recent clinic attendance Exclusion Criteria: - Subjects who in the investigator's opinion are unlikely to complete the 48 week trial period - Currently active opportunistic disease or documented wasting syndrome - Currently receiving chemotherapy for malignancy - Subjects who in the opinion of the investigator are unlikely to retain viral response after switching based on treatment or transmission history - Currently receiving an insulin sensitising agent (glitazone or metformin) - Anabolic steroids in the last 16 weeks other than testosterone at replacement doses (<250mg/2 weekly) - Growth hormone use in the last 16 weeks - Statin therapy (HMG CoA reductase inhibitor) commenced in the last 16 weeks (patients stable on statins my be included) - Current alcohol or illicit drug use which, in the opinion of the investigator, may interfere with the subjects' ability to comply with the dosing schedule and protocol evaluations - Receiving concurrent medications that - in the opinion of the investigator and according to drug product labelling - will result in clinically significant interactions with tenofovir or abacavir - Pregnant or breast feeding - Previously received more than 3 months zidovudine monotherapy Inclusion Criteria: - Subjects who are male or female > 18 years of age - Subjects who are HIV-1 infected as documented by a licensed HIV-1 antibody ELISA - Female subjects of childbearing potential must have a negative serum pregnancy test (beta-HCG) within 28 days of trial day 1. --- K65R ---

Women of childbearing potential must agree to use a barrier method of contraception - Female subjects must not be pregnant or lactating - Subjects who in the opinion of the investigator have the ability to understand and provided written informed consent to participate in the trial - Subjects who in the opinion of the investigator have clinical lipoatrophy at > 1 body/facial site - Subjects currently receiving nucleoside analogue regimen including stavudine (d4T) or zidovudine (ZDV) - Subjects who are stable on current therapy for >16 weeks - Subjects with no prior exposure to tenofovir, abacavir, or adefovir - Subjects with no known K65R, 69S mutations or 3 or more thymidine analogue mutations - Subjects with documented viral load <50 copies/ml on 2 consecutive occasions including most recent clinic attendance Exclusion Criteria: - Subjects who in the investigator's opinion are unlikely to complete the 48 week trial period - Currently active opportunistic disease or documented wasting syndrome - Currently receiving chemotherapy for malignancy - Subjects who in the opinion of the investigator are unlikely to retain viral response after switching based on treatment or transmission history - Currently receiving an insulin sensitising agent (glitazone or metformin) - Anabolic steroids in the last 16 weeks other than testosterone at replacement doses (<250mg/2 weekly) - Growth hormone use in the last 16 weeks - Statin therapy (HMG CoA reductase inhibitor) commenced in the last 16 weeks (patients stable on statins my be included) - Current alcohol or illicit drug use which, in the opinion of the investigator, may interfere with the subjects' ability to comply with the dosing schedule and protocol evaluations - Receiving concurrent medications that - in the opinion of the investigator and according to drug product labelling - will result in clinically significant interactions with tenofovir or abacavir - Pregnant or breast feeding - Previously received more than 3 months zidovudine monotherapy Lipodystrophy Lipodystrophy This is a phase II, open-label, multicentre, randomised, two-arm study of 48 weeks duration. --- K65R ---

Primary Outcomes

Measure: Change in total limb fat mass by DEXA scan

Time: 24 and 48 weeks

Secondary Outcomes

Measure: Change in VAT by single slice L4 abdominal CT scan

Time: 24 and 48 weeks

Measure: Change in viral load measurements and CD4 cell count

Time: 24 and 48 Weeks

Measure: Change in fasting cholesterol and triglycerides

Time: 24 and 48 Weeks

Measure: Change in blood insulin and fasting glucose

Time: 24 and 48 Weeks

Measure: Change in blood lactate and anion gap

Time: 24 and 48 Weeks

Measure: Change in bone mineral density by DEXA scan

Time: 24 and 48 Weeks

Measure: Incidence of adverse events

Time: Upto 48 weeks

38 Phase 2B Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate Tablet and Emtricitabine/Tenofovir Disoproxil Fumarate Tablet for the Prevention of HIV Infection in Women

A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) are oral, FDA-approved, anti-HIV drugs, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the safety and effectiveness of daily tenofovir 1% gel compared to a vaginal placebo gel, and the safety and effectiveness of oral TDF and oral FTC/TDF compared to an oral placebo in preventing HIV infection among women at risk for sexually transmitted infections.

NCT00705679
Conditions
  1. HIV Infections
Interventions
  1. Drug: Emtricitabine/tenofovir disoproxil fumarate
  2. Drug: Emtricitabine/tenofovir disoproxil fumarate placebo
  3. Drug: Tenofovir disoproxil fumarate
  4. Drug: Tenofovir disoproxil fumarate placebo
  5. Drug: Tenofovir 1% vaginal gel
  6. Drug: Tenofovir placebo
MeSH:Infection HIV Infections Acquired Immunodeficiency Syndrome

The primary resistance mutations for the study were pre-defined as K65R and K70E (which confer resistance to TDF), and M184I and M184V (which confer resistance to FTC), for their potential to cause a decrease in susceptibility to the study drug. --- K65R ---

K65R, K70E, and M184I were not detected in HIV-1 from any HIV-1 seroconverters while on study product. --- K65R ---

Primary Outcomes

Description: Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up.

Measure: Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms

Time: For up to 30 months of follow-up

Description: Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).

Measure: Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms

Time: For up to 30 months of follow-up

Description: This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).

Measure: Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms

Time: For up to 30 months of follow-up

Description: Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up. Note that the data for both of these arms were censored on the date when sites were asked to discontinue treatment in the oral TDF group.

Measure: Person-years of Follow-up of Oral TDF and Oral Placebo Arms

Time: For up to 30 months of follow-up

Description: Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).

Measure: Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms

Time: For up to 30 months of follow-up

Description: This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).

Measure: Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms

Time: For up to 30 months of follow-up

Description: Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up.

Measure: Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms

Time: For up to 30 months of follow-up

Description: Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).

Measure: Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms

Time: For up to 30 months of follow-up

Description: This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).

Measure: Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms

Time: For up to 30 months of follow-up

Description: This measure describes the number of participants with elevated serum creatinine levels, the only safety outcome of concern where a significant difference was detected between an active arm and the corresponding placebo arm.

Measure: Extended Safety of Daily Tenofovir 1% Gel, Oral TDF, and Oral FTC/TDF in Women at Risk for Sexually Transmitted HIV Infection Based on Occurrence of Grade 2, 3, and 4 Adverse Events

Time: Throughout study, up to 2.5 years

Secondary Outcomes

Description: The primary resistance mutations for the study were pre-defined as K65R and K70E (which confer resistance to TDF), and M184I and M184V (which confer resistance to FTC), for their potential to cause a decrease in susceptibility to the study drug. K65R, K70E, and M184I were not detected in HIV-1 from any HIV-1 seroconverters while on study product. The number of HIV-1 seroconverters while on study with the M184V resistance mutation are reported for this outcome measure.

Measure: Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product

Time: Throughout study, up to 2.5 years

39 A Prospective, Randomized, Multicenter, Open-Label Study to Compare the Efficacy and Safety of Simplifying From a Regimen of Atazanavir (ATV) + Ritonavir (RTV) + Tenofovir/Emtricitabine to ATV + Abacavir/Lamivudine Without RTV in Virologically Suppressed, HIV-1 Infected, HLA-B*5701 Negative Subjects

This study is designed to compare the efficacy and safety of simplifying therapy from a regimen of atazanavir (ATV) + ritonavir (RTV) + tenofovir/emtricitabine (TDF/FTC) to a regimen of ATV + abacavir sulfate/lamivudine (ABC/3TC) without RTV in virologically suppressed, HIV-1 infected, HLA-B*5701 negative subjects for 48 weeks.

NCT01102972
Conditions
  1. Infection, Human Immunodeficiency Virus
Interventions
  1. Drug: Reyataz + Norvir + Truvada
  2. Drug: Reyataz + Epzicom
MeSH:Acquired Immunodeficiency Syndrome HIV Infections

- Subject is virologically suppressed on ATV + RTV + TDF/FTC defined as HIV-1 RNA K65R, K70E, L74V, M184I/V or Y115F, a combination of two or more thymidine analog mutations including M41L, D67N, K70R, K219Q or E that include changes at either L210 or T215), or 3 or more of the following HIV-1 protease mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50, I54, A71, G73, V77, V82, I84, N88, and L90 - Subject is HLA-B*5701 positive - Subject has hypersensitivity to any component of the study drugs - SUbject is pregnant or breastfeeding - Subject is enrolled in one or more investigational drug protocols within 30 days of screening - Subject has an active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial - Subject has ongoing clinically relevant hepatitis at screening and/or positive for Hepatitis B (+ HbsAg) - Subject has a creatinine clearance <50 mL/min via the Cockcroft-Gault method - Subject has a verified Grade 4 laboratory abnormality at screening unless the Investigator can provide a compelling explanation (e.g. --- K65R ---

Primary Outcomes

Description: The percentage of PAR with HIV-1 RNA virus <50 c/mL determined from blood samples drawn at Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment. Per TLOVR algorithm, responders were PAR with confirmed viral load <50 c/mL who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <50 c/mL, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 50 c/mL, or had an unconfirmed HIV RNA of at least 50 c/mL at the last visit.

Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c)/Milliliter (mL) at the Week 24 Visit: TLOVR Analysis

Time: Week 24

Secondary Outcomes

Description: The percentage of PAR with HIV-1 RNA virus <50 c/mL determined from blood samples drawn through Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.

Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 c/mL at the Week 24 Visit: Observed, M/D=F, and SNAPSHOT Analyses

Time: Week 24

Description: The percentage of PAR with HIV-1 RNA virus <50 c/mL determined from blood samples drawn at Week 48 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.

Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 c/mL at the Week 48 Visit: TLOVR, Observed, M/D=F, and SNAPSHOT Analyses

Time: Week 48

Description: The percentage of PAR with HIV-1 RNA virus <400 c/mL determined from blood samples drawn at Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment. Per TLOVR algorithm, responders were PAR with confirmed viral load <400 c/mL who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <400 c/mL, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 400 c/mL, or had an unconfirmed HIV RNA of at least 400 c/mL at the last visit.

Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: TLOVR Analysis

Time: Week 24

Description: The percentage of PAR with HIV-1 RNA virus <400 c/mL determined from blood samples drawn at Week 48 was tabulated by treatment arm with stratification by initial antiretroviral treatment. Per TLOVR algorithm, responders were PAR with confirmed viral load <400 c/mL who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <400 c/mL, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 400 c/mL, or had an unconfirmed HIV RNA of at least 400 c/mL at the last visit.

Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: TLOVR Analysis

Time: Week 48

Description: The percentage of PAR with HIV-1 RNA virus <400 c/mL determined from blood samples drawn at Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.

Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: Observed, MD=F, and SNAPSHOT Analyses

Time: Week 24

Description: The percentage of PAR with HIV-1 RNA virus <400 c/mL determined from blood samples drawn at Week 48 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.

Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: Observed, MD=F, and SNAPSHOT Analyses

Time: Week 48

Description: Change from Baseline was calculated as the Week 24 value minus the Baseline value. Blood was drawn to analyze for plasma HIV viral load.

Measure: Change From Baseline in HIV-1 RNA at Week 24

Time: Baseline and Week 24

Description: Change from Baseline was calculated as the Week 48 value minus the Baseline value. Blood was drawn to analyze for plasma HIV viral load.

Measure: Change From Baseline in HIV-1 RNA at Week 48

Time: Baseline and Week 48

Description: Blood was drawn to analyze for CD4+ cell count. A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from Baseline was calculated as the Week 24 value minus the Baseline value.

Measure: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline and Week 24

Description: Blood was drawn to analyze for CD4+ cell count. A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from Baseline was calculated as the Week 48 value minus the Baseline value.

Measure: Change From Baseline in CD4+ Cell Count at Week 48

Time: Baseline and Week 48

Description: Triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured at Week 24. A Fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 24 value minus the Baseline value for each parameter.

Measure: Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 24

Time: Baseline and Week 24

Description: A Fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 24 value minus the Baseline value.

Measure: Change From Baseline in Cholesterol/HDL Ratio at Week 24

Time: Baseline and Week 24

Description: Triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured or calculated at Week 48. A fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 48 value minus the Baseline value for each parameter.

Measure: Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 48

Time: Baseline and Week 48

Description: A fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 48 value minus the Baseline value for each parameter.

Measure: Change From Baseline in Cholesterol/HDL Ratio at Week 48

Time: Baseline and Week 48

Description: The number of participants that failed to remain virologically suppressed through 24 weeks on treatment was assessed. Viral failure is defined per protocol as confirmed HIV-1 RNA >=400 c/mL.

Measure: Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 24

Time: From Baseline to Week 24

Description: The number of participants that failed to remain virologically suppressed from baseline through 48 weeks on treatment was assessed. Viral failure is defined per protocol as confirmed HIV-1 RNA >=400 c/mL.

Measure: Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 48

Time: From Baseline to Week 48

Description: Death and clinical disease progression (as per CDC classification) were assessed from Baseline through Week 48. Disease progression is defined as progression from CDC Class A to B, Class A to C, or from Class B to C. AIDS CDC classifications are: Class A, Asymptomatic/lymphadenopathy/acute HIV; Class B, Symptomatic, not AIDS; Class C, AIDS indicator conditions. The CDC categorization of HIV/AIDS is based on the lowest documented CD4 cell count (Class A, >=500 cells per microliter [µl]; Class B, 200-499 cells/µl; Class C, <200 cells/µl) and on previously diagnosed HIV-related conditions.

Measure: Number of Participants Who Experienced Death and/or Disease Progression

Time: From Baseline to Week 48

Description: A blood sample was drawn for particiapants with confirmed VF >=400 c/mL. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at Baseline. New resistance-associated viral mutations defined by the International Acquired Immunodeficiency Syndrome Society-United States of America guidelines present at the time of failure were tabulated by drug class. NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Measure: Number of Confirmed Virologic Failure (VF) Participants (PAR) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 24

Time: From Baseline to Week 24

Description: A blood sample was drawn for particiapants with confirmed VF >=400 c/mL. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at Baseline. New resistance-associated viral mutations defined by the International Acquired Immunodeficiency Syndrome Society-United States of America guidelines present at the time of failure were tabulated by drug class. NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Measure: Number of Confirmed Virologic Failure (VF) Participants (PAR) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 48

Time: From Baseline to Week 48

Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at Baseline.

Measure: Number of Confirmed Virologic Failure Participants (PAR) From Baseline Through Week 24 With the Indicated Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Tenofovir, Emtricitabine, Atazanavir, or Ritonavir

Time: From Baseline to Week 24

Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at Baseline.

Measure: Number of Confirmed Virologic Failure Participants (PAR) From Baseline Through Week 48 With the Indicated Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Tenofovir, Emtricitabine, Atazanavir, or Ritonavir

Time: From Baseline to Week 48

Description: The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 is a descriptive terminology that can be utilized for AE reporting. A grading (severity) scale is provided for each AE. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1, mild AE; Grade 2, moderate AE; Grade 3, severe AE; Grade 4, life-threatening or disabling AE; Grade 5, death related to the AE.

Measure: Number of Participants With the Indicated Grade 2 to Grade 4 Adverse Events (AEs) Occurring at a Frequency of >=3% in Either Treatment Group

Time: From Baseline to Week 24

Description: The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 is a descriptive terminology that can be utilized for AE reporting. A grading (severity) scale is provided for each AE. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1, mild AE; Grade 2, moderate AE; Grade 3, severe AE; Grade 4, life-threatening or disabling AE; Grade 5, death related to the AE.

Measure: Number of Participants With the Indicated Grade 2 to Grade 4 Adverse Events (AEs) Occurring at a Frequency of >=3% in Either Treatment Group

Time: From Baseline to Week 48

40 Open Label Randomized Controlled Trial to Assess the Impact of Prophylactic Exposure to Tenofovir Gel on the Efficacy of Subsequent Tenofovir-containing Antiretroviral Therapy on Viral Suppression

The HIV/AIDS pandemic remains among the investigators greatest public health challenges. In the absence of an effective vaccine, focus has shifted to other prevention strategies such as pre-exposure prophylaxis. Tenofovir, with potent activity against retroviruses [1], was developed for oral use as Viread®, which is widely used for HIV treatment. The efficacy of Viread® has been demonstrated in treatment-experienced and naïve patients [2,3]. In antiretroviral-naive patients, the combination of tenofovir with lamivudine and efavirenz has been classified as a preferred regimen in the Department of Health and Human Services treatment guidelines[4], and has been adopted by the South African Department of health as the first line regimen in treatment-naïve HIV infected patients since April 2010. The durability of antiviral response, favourable resistance profile, once daily dosing, and excellent long term safety profile of tenofovir [5], makes this drug an attractive option in both treatment and prevention regimens and its long half-life [6], made it an ideal choice as the first antiretroviral drug to be formulated as a microbicide gel. The CAPRISA 004 study conducted in South Africa which tested the effectiveness and safety of 1% tenofovir gel showed that the use of tenofovir in a gel formulation reduced HIV acquisition by 39% overall, and by 54% in women with high gel adherence [7]. There have been concerns raised regarding the use of tenofovir in both PrEP and treatment regimens due to the potential for selection of viral mutations and development of resistance in patients who have become HIV-infected while on PrEP. There have been no studies conducted to determine whether using tenofovir in pre-exposure prophylaxis affects treatment outcomes in patients who later use tenofovir, which is part of the first line ART of South Africa. This study aims to determine whether prophylactic exposure to tenofovir gel alters the therapeutic response to a tenofovir containing antiretroviral regimen.

NCT01387022
Conditions
  1. Antiretroviral Treatment Outcomes
Interventions
  1. Drug: Tenofovir, lamivudine and efavirenz

Tenofovir Resistance, Defined as Presence of K65R, K70E or Any of the TAMS Mutations. --- K65R ---

Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death Secondary Endpoints: 1. Change in CD4+ cell count from the earliest post-infection timepoint to the time of randomisation to 12, 24 and 36 months post-randomisation 2. Tenofovir resistance, defined as presence of K65R, K70E or any of the TAMS mutations. --- K65R ---

Primary Outcomes

Description: Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death

Measure: The Antiretroviral Treatment Failure Rate at 12 Months.

Time: 12 months post ART intiation or until time of death

Secondary Outcomes

Description: Difference between 12 months and randomisation CD4+ count was calculated and then summarised

Measure: Change in CD4+ Cell Count From Randomisation to 12 Months Post-randomisation

Time: Measured at 12 months post ART initiation

Measure: Tenofovir Resistance, Defined as Presence of K65R, K70E or Any of the TAMS Mutations

Time: From randomisation until either time of termination or time of death

Measure: Reported Adverse Events With Severity Grades 3 and 4 Based on the DAIDS Toxicity Grading Tables

Time: From randomisation until either time of termination or time of death

Description: We will assess whether exposure to tenofovir gel at the time of HIV acquisition alters the subsequent humoral and cellular immune responses following antiretroviral treatment initiation

Measure: Cellular and Humoral Immune Responses

Time: 3 years

Measure: Genital Viral Shedding (Viral Load on Tear Flow)

Time: 3 years

41 Artery Elasticity After Switch From Epzicom to Truvada

Recent research as suggested that use of the HIV medication abacavir (Ziagen, or co-formulated with lamivudine as Epzicom) may increase risk for heart disease, though findings from multiple studies have been inconsistent. This pilot study will examine vascular function, a marker of heart disease risk, among patients taking abacavir as part of their HIV medications and are then randomized to: 1) switch to tenofovir, another HIV medication, or 2) continue to take abacavir.

NCT00998582
Conditions
  1. HIV Infections
Interventions
  1. Drug: Tenofovir disoproxil
MeSH:HIV Infections

- Males and females (of childbearing potential) must agree to avoid pregnancy by sexual abstinence, or utilization of a highly effective method of birth control throughout the study period and for 30 days following discontinuation of study drug (refer to Appendix A for definitions of 'childbearing potential' and 'highly effective method of birth control') Exclusion Criteria: - Subjects with known resistance to abacavir, lamivudine, tenofovir DF, or emtricitabine at anytime in the past (including but not limited to K65R, L74V/I, M184V/I, or thymidine analog mutations). --- K65R ---

Primary Outcomes

Description: Small artery elasticity is a measure of vascular function, estimated through analysis of the blood pressure waveform. A sensor is placed on wrist over the radial pulse. The blood pressure waveform of the pulse is recorded and analyzed the elasticity, or compliance, of the small (and large) vasculature. Impaired artery elasticity, or increased stiffness, is an early sign of vascular disease that predicts risk for future cardiovascular events.

Measure: Change in Small Artery Elasticity (mL/mmHg x100) From Baseline to Week 24

Time: Change from baseline to 24 weeks

Description: Large artery elasticity is a measure of vascular function, estimated through analysis of the blood pressure waveform. A sensor is placed on wrist over the radial pulse. The blood pressure waveform of the pulse is recorded and analyzed the elasticity, or compliance, of the large (and small) vasculature. Impaired artery elasticity, or increased stiffness, is an early sign of vascular disease.

Measure: Outcome Was Change in Large Artery Elasticity (mL/mmHg x100) From Baseline to Week 24

Time: Change from baseline to 24 weeks

42 A Study in Underrepresented Patient Population or Regimen Tolerability: SUPPoRT

The hope of this study is to gather data and information about the tolerability and effectiveness of Lexiva versus Sustiva in patients who have have been generally underrepresented in clinical trials.

NCT00727597
Conditions
  1. Human Immunodeficiency Virus Infections
Interventions
  1. Drug: Efavirenz 600mg
  2. Drug: Boosted Lexiva
MeSH:Acquired Immunodeficiency Syndrome HIV Infections

v. Sterilization (female subject or male partner of female subject) Exclusion Criteria: Screening HIV-1 genotype indicating the presence of any of the following mutations in the reverse transcriptase (RT) region: K65R, L74V, K103N, Y115F, Y181C/I, Y188C/L/H or G190S/A, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, associated with resistance to abacavir, lamivudine, or efavirenz; OR within the protease region, detection of any of the following mutations associated with resistance to fosamprenavir or ritonavir: I50V, I54L/M, I84V, or the combination of the two mutations V32I+I147V Positive for Hepatitis B surface antigen (HBsAg+) Requirement for active treatment for hepatitis C virus infection, as indicated by both a positive Hepatitis C Virus serology AND either: 1. Decompensated liver disease, or 2. Aspartate aminotransferase (AST) >3X the upper limit of normal (ULN), or 3. Alanine aminotransferase (ALT) >3X the ULN Currently pregnant, intending to become pregnant during the study period, or breast-feeding Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), any vaccinations, systemic cytotoxic chemotherapy, or investigational therapy within 28 days prior to study entry. --- K65R ---

Primary Outcomes

Description: Subjects were randomized and initiated treatment on one of the antiretroviral arms(FPV/r or EFV) at study Entry visit. Subjects would be switched for the follwing reasons: To resolve a Grade 3 or 4 Adverse Event The subject experienced a virologic failure (as defined in section 3.6.2) The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide)

Measure: Number of Subjects Needing to Switch Comparator Drugs (FPV/r or EFV)

Time: 96 weeks

Measure: Number of Subjects Developing Any Treatment-related Grade 3-4 Adverse Events

Time: 96 weeks

43 A Prospective, Randomized, Open Label Phase IV Study to Evaluate the Rationale of Switching From Fixed Dose Abacavir (ABC)/Lamivudine (3TC) to Fixed Dose Tenofovir DF (TDF)/Emtricitabine (FTC) in Virologically Suppressed, HIV-1 Infected Patients Maintained on a Ritonavir Boosted Protease Inhibitor Containing Antiretroviral Regimen

This protocol describes a prospective, randomized, open-label, multicenter study to evaluate the safety and efficacy of switching from fixed dose abacavir (ABC)/lamivudine (3TC) to fixed dose emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in virologically suppressed, human immunodeficiency virus type 1 (HIV-1) infected subjects maintained on a ritonavir-boosted protease inhibitor (PI/r)-containing antiretroviral (ARV) regimen. Duration of treatment is 48 weeks.

NCT00724711
Conditions
  1. HIV Infection
Interventions
  1. Drug: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)
  2. Drug: abacavir (ABC)/lamivudine (3TC)
MeSH:HIV Infections

- Adequate renal function defined as a calculated CLcr greater than or equal to 50 mL/min according to the Cockcroft-Gault formula - Negative serum pregnancy test (females of childbearing potential only) - Hepatic transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 5 X upper limit of normal - Males and females (of childbearing potential, ie, a non-menopausal female or a female with menopause < 2 years, and who has not had a hysterectomy, bilateral oophorectomy, or medically documented ovarian failure; this definition includes a young woman who has not yet started menstruating), and must agree to avoid pregnancy by sexual abstinence, or utilization of a highly effective method of birth control throughout the study period and for 30 days following discontinuation of study drug - The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures Exclusion Criteria: - Subjects receiving ABC/3TC and a PI without ritonavir - Subjects receiving other ARV agents (eg, 2 protease inhibitors boosted with low-dose ritonavir (ie, "double-boosted PI regimens"), nonnucleoside reverse transcriptase inhibitors [NNRTIs], integrase inhibitors, TDF, or other nucleoside reverse transcriptase inhibitor [NRTIs]) in addition to ABC/3TC and a ritonavir-boosted protease inhibitor - Have known resistance to any of the study agents at any time in the past including NRTI resistance mutations (including but not limited to K65R, L74V/I, M184V/I, or thymidine analog mutations) and/or PI resistance mutations - A new acquired immunodeficiency syndrome (AIDS) defining condition diagnosed (with the exception of CD4 criteria) within 30 days of baseline - Previous therapy with agents with systemic myelosuppressive, pancreatoxic, hepatotoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment - Proven or suspected acute hepatitis in the 30 days prior to study entry - Anticipated need to initiate drugs during the study that are contraindicated with protease inhibitors (except upon approval by Gilead) - Receiving ongoing therapy with any of the following (administration of any of the following medications must be discontinued at least 30 days prior to the Baseline visit and for the duration of the study period): - Nephrotoxic agents (aminoglycoside antibiotics, amphotericin B, cidofovir, cisplatin, foscarnet, intravenous pentamidine, other agents with significant nephrotoxic potential) - Adefovir dipivoxil - Probenecid - Systemic chemotherapeutic agents (ie, cancer treatment medications) - Systemic corticosteroids - Interleukin-2 (IL-2) - Investigational agents (except upon approval by Gilead) - Pregnant or lactating subjects - Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication - Current alcohol or substance abuse judged by the investigator to potentially interfere with subject adherence - Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. --- K65R ---

Primary Outcomes

Description: The percentage of participants with HIV-1 RNA < 200 copies/mL based on TLOVR algorithm at Week 48 was summarized. Participants were considered nonresponders in the TLOVR analysis if they experienced virologic rebound prior to or at Week 48, discontinued study before Week 48, or added a new antiretroviral (ARV) agent prior to completion of the study. Virologic rebound was defined as 2 consecutive HIV-1 RNA values >= 200 copies/mL or the last HIV-1 RNA value >= 200 copies/mL followed by discontinuation from the study.

Measure: Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) < 200 Copies/mL Through Week 48 Based on Time to Loss of Virologic Response (TLOVR) Algorithm

Time: Baseline to 48 weeks

Secondary Outcomes

Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 200 copies/mL at Week 48 was summarized. Pure virologic response was the percentage of subjects who did not have a virologic rebound. Virologic rebound was defined as two consecutive HIV-1 RNA values >= 200 copies/mL or the last HIV-1 RNA value >= 200 copies/mL followed by discontinuation from the study.

Measure: Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 200 Copies/mL Through Week 48

Time: Baseline to 48 weeks

Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 48 was summarized. Pure virologic response was the proportion of participants who did not have a virologic rebound. Virologic rebound was defined as two consecutive HIV-1 RNA values >= 50 copies/mL or the last HIV-1 RNA value >= 50 copies/mL followed by discontinuation from the study.

Measure: Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 50 Copies/mL Through Week 48

Time: Baseline to 48 weeks

Description: The percentage of participants with HIV-1 RNA < 200 copies/mL at Week 48 was summarized.

Measure: Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 48

Time: 48 weeks

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was summarized.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48

Time: 48 weeks

Description: Change = Week 48 value minus baseline value

Measure: Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48

Time: Baseline to 48 weeks

Description: Change = Week 48 value minus baseline value

Measure: Change From Baseline Calculated Creatinine Clearance (CLcr) Using Ideal Body Weight by Cockcroft-Gault Method at Week 48

Time: Baseline to 48 weeks

Description: Change = Week 48 value minus baseline value

Measure: Change From Baseline Estimated Glomerular Filtration Rate (eGFR) by Modified Diet in Renal Disease (MDRD) at Week 48

Time: Baseline to 48 weeks

Description: Change = Week 48 value minus baseline value

Measure: Change From Baseline Fasting Glucose at Week 48

Time: Baseline to 48 weeks

Description: Change = Week 48 value minus baseline value

Measure: Change From Baseline Fasting Lipid Parameters at Week 48

Time: Baseline to 48 weeks

Description: Change = Week 48 value minus baseline value

Measure: Change From Baseline Ratio of Fasting Total Cholesterol Over High-density Lipoprotein (HDL) Cholesterol at Week 48

Time: Baseline to 48 weeks

Description: Change = Week 48 value minus baseline value

Measure: Change From Baseline C-Reactive Protein at Week 48

Time: Baseline to 48 weeks

Description: Change = Week 48 value minus baseline value

Measure: Change From Baseline Fibrinogen at Week 48

Time: Baseline to 48 weeks

Description: Change = Week 48 value minus baseline value

Measure: Change From Baseline Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor Necrosis Factor-alpha (TNF-alpha) at Week 48

Time: Baseline to 48 weeks

44 A Phase 3b Randomized, Open-label, Controlled Study of the Efficacy, Safety and Tolerability of 12 Weeks of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Subjects Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment, the HIV/HCV Co-STARs Study (Co-infection Treatment With Single Tablet Antiviral Regimens)

This study will evaluate efficacy of ledipasvir/sofosbuvir (LDV/SOF) and safety and tolerability of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or emtricitabine/rilpivirine/tenofovir alafenamide (F/R/TAF) from the current antiretroviral (ARV) therapy and in virologically-suppressed, HIV-1/HCV co-infected participants.

NCT02707601
Conditions
  1. HIV-1 Infection
  2. HCV Infection
Interventions
  1. Drug: E/C/F/TAF
  2. Drug: F/R/TAF
  3. Drug: LDV/SOF
MeSH:Infection Communicable Diseases Hepatitis C

- Plasma HIV-1 RNA level < 50 copies/mL at the screening visit - Have no documented resistance to any of the HIV study agents at time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I, or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). --- K65R ---

Primary Outcomes

Description: Sustained Virologic Response (SVR12) was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.

Measure: Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12)

Time: HCV Posttreatment Week 12

Secondary Outcomes

Description: SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping LDV/SOF treatment.

Measure: Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4)

Time: HCV Posttreatment Week 4

Description: The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm

Time: 24 weeks after start of HIV treatment

Measure: Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment

Time: Up to 32 weeks plus 30 days

45 Doravirine for Persons With Excessive Weight Gain on Integrase Inhibitors and Tenofovir Alafenamide (The Do IT Study)

The primary purpose of this study is to see if people with HIV who had a significant weight gain after starting INSTI (integrase strand transfer inhibitor)+TAF/FTC (tenofovir alafenamide/emtricitabine) (TAF/3TC (lamivudine)) regimen could either slow their rate of weight gain or lose weight within about 1 year if they switch to a regimen containing doravirine (DOR; a newer, non-nucleoside reverse transcriptase inhibitor medication). The study will also try to see if participants changing from TAF/FTC (or TAF/3TC) to TDF/FTC (or TDF/3TC) will experience less additional weight gain or a reduction in overall body weight at 48 weeks compared to persons continued on an INSTI + TAF/FTC (or TAF/3TC) combination. INSTINs assessed in A5391 include bictegravir (BIC), dolutegravir (DTG), or raltegravir (RAL). Additionally, the study will see whether a change in ART can affect things like waist circumference, metabolic and cardiovascular health, fat and lean mass body composition, bone health, and maintenance of virologic suppression. Finally, the study will look at the safety and tolerability of DOR plus either TAF/FTC (or TAF/3TC) versus TDF/FTC (or TDF/3TC).

NCT04636437
Conditions
  1. HIV Infections
Interventions
  1. Drug: Doravirine 100 Mg
  2. Drug: Tenofovir alafenamide/emtricitabine
  3. Drug: tenofovir alafenamide/lamivudine
  4. Drug: Integrase strand transfer inhibitors
  5. Drug: tenofovir disproxil fumarate/emtricitabine
  6. Drug: tenofovir disproxil fumarate/lamivudine
MeSH:Weight Gain
HPO:Increased body weight

- Aspartate aminotransferase (AST) (SGOT) <3x ULN - Alanine aminotransferase (ALT) (SGPT) <3x ULN Exclusion Criteria: - Historical or current evidence of the K65R/E/N or M184V/I mutations (for participants who have undergone HIV-1 genotyping), due to the potential for viral rebound after switch from an INSTI- to NNRTI-based regimen. --- K65R ---

Primary Outcomes

Measure: Change (percent) in body weight (kg) from entry to week 48

Time: Day 0 to week 48

Secondary Outcomes

Measure: Change (percent) in body weight (kg) from entry to week 24

Time: Day 0 to week 24

Measure: Change (absolute) in waist circumference from entry to weeks 24 and 48

Time: Day 0 to weeks 24 and 48

Measure: Change (absolute) in fasting cardiometabolic parameters (glucose, insulin, HOMA-IR, triglycerides, LDL, HDL) from entry to weeks 24 and 48

Time: Day 0 to weeks 24 and 48

Description: Proportion of participants with confirmed plasma HIV-1 RNA >200 copies/mL

Measure: Occurrence of confirmed plasma HIV-1 RNA >200 copies/mL

Time: At day 0, weeks 4, 12, 24, and 48

Description: Proportion of participants with Grade ≥3 AEs or >10% reduction in CrCl as estimated by the CKD-EPI equation

Measure: Occurrence of Grade ≥3 AEs or >10% reduction in CrCl as estimated by the CKD-EPI equation

Time: Day 0 to week 48

Description: Proportion of participants who prematurely discontinued study treatment

Measure: Occurrence of premature discontinuation of study treatment

Time: Day 0 to week 48

Measure: Change (percent) in total fat from entry to week 48, measured by DEXA.

Time: Day 0 to week 48

Measure: Change (percent) in lean mass from entry to week 48, measured by DEXA.

Time: Day 0 to week 48

Measure: Change (percent) in trunk fat from entry to week 48, measured by DEXA.

Time: Day 0 to week 48

Measure: Change (percent) in limb fat from entry to week 48, measured by DEXA.

Time: Day 0 to week 48

Measure: Change (percent) in appendicular lean mass from entry to week 48, measured by DEXA.

Time: Day 0 to week 48

Measure: Change (percent) in DEXA hip and lumbar spine bone mineral density from entry to week 48

Time: Day 0 to week 48

46 A Phase 3b Open-Label Pilot Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) in Virologically-Suppressed HIV-1 Infected Adult Subjects Harboring the Archived Isolated NRTI Resistance Mutation M184V/M184I

The primary objective of the study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) after switching from a stable regimen consisting of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) plus a third antiretroviral (ARV) agent in participants harboring the archived nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance mutation M184V and/or M184I in human immunodeficiency virus (HIV) -1 reverse transcriptase. This is a two part study. If the rate of virologic failure in Part 1 is deemed acceptable, once the internal data monitoring committee officially completes the interim review, the study will continue to Part 2.

NCT02616029
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: E/C/F/TAF

- Proviral deoxyribonucleic acid (DNA) test must not have additional exclusion resistance mutations against PIs, NRTIs and INSTIs - Part 1: Historical genotype report must show mutation M184V and/or M184I in reverse transcriptase WITHOUT any other NRTI resistance mutation (including thymidine analogue-associated mutations [TAMs] [TAMs are: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E/N/R], K65R, K70E, T69 insertion, and Q151M mutation complex [A62V, V75I, F77L, F116Y, Q151M]) - Part 2 (after the interim efficacy review): Historical genotype report must show M184V and/or M184I in reverse transcriptase WITH or WITHOUT 1 or 2 TAMs. --- M184V --- --- M184I --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215Y --- --- K219Q --- --- K65R ---

Evidence of K65R, K70E, T69 insertion and/or Q151M mutation complex will not be eligible - Currently receiving an ARV regimen consisting of FTC/TDF or ABC/3TC in combination with one third ARV agent for ≥ 6 consecutive months preceding the screening visit - Documented plasma HIV-1 ribonucleic acid (RNA) levels < 50 copies/mL for ≥ 6 months preceding the screening visit - Plasma HIV-1 RNA levels < 50 copies/mL at screening visit - Estimated glomerular filtration rate (GFR) ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance - A female individual is eligible to enter the study if it is confirmed that she is: - not pregnant - of non-childbearing potential - stopped menstruating for ≥ 12 months - of childbearing potential and agrees to utilize the protocol-specified method of contraception or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs - Male individuals must agree to use the protocol-specified method(s) of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from screening throughout the study period and for 30 days following the last study drug dose - Male individuals must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose Key Exclusion Criteria: - Individuals will have no evidence of previous virologic failure on a PI/r or INSTI-based regimen (with or without resistance to either class of ARV). --- K65R ---

Primary Outcomes

Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 12 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

Measure: Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 12 as Defined by Pure Virologic Response (PVR)

Time: Week 12

Secondary Outcomes

Description: Development of new resistance mutations was assessed in participants who developed virologic failure, defined as 2 consecutive HIV-1 RNA result ≥ 50 copies/mL at any point in the study or with HIV-1 RNA ≥ 50 copies/mL at last visit.

Measure: Percentage of Participants With Emergence of New Mutations in HIV-1 Reverse Transcriptase and Integrase

Time: Day 1 up to 48 weeks

Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 24 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using PVR

Time: Week 24

Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 48 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using PVR

Time: Week 48

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 71 and 98 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the FDA Snapshot Analysis

Time: Week 12

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 24 window was between Day 141 and 210 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the FDA Snapshot Analysis

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 295 and 378 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA Snapshot Analysis

Time: Week 48

Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 12 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 71 and 98 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 12 Using the FDA Snapshot Analysis

Time: Week 12

Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 24 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 24 window was between Day 141 and 210 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 24 Using the FDA Snapshot Analysis

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 48 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 295 and 378 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 Using the FDA Snapshot Analysis

Time: Week 48

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the Missing = Failure (M = F) Approach

Time: Week 12

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the M = F Approach

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = F Approach

Time: Week 48

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the Missing = Excluded (M = E) Approach

Time: Week 12

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the M = E Approach

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach

Time: Week 48

Measure: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 12

Time: Baseline (Day 1); Week 12

Measure: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline (Day 1); Week 24

Measure: Change From Baseline in CD4+ Cell Count at Week 48

Time: Baseline (Day 1); Week 48

Measure: Change From Baseline in CD4 Percentage (%) at Week 12

Time: Baseline (Day 1); Week 12

Measure: Change From Baseline in CD4 % at Week 24

Time: Baseline (Day 1); Week 24

Measure: Change From Baseline in CD4 % at Week 48

Time: Baseline (Day 1); Week 48

47 A Phase 3b, Randomized, Open-Label Study to Evaluate Switching From a Tenofovir Disoproxil Fumarate (TDF) Containing Regimen to Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Infected Subjects Aged ≥ 60 Years

The primary objective of this study is to evaluate the safety of elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (E/C/F/TAF) relative to unchanged current antiretroviral therapy (ART) by assessing spine and hip bone mineral density (BMD) measured at Week 48 in virologically-suppressed, HIV-1 infected participants aged ≥ 60 years.

NCT02616783
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: E/C/F/TAF
  2. Drug: TDF
  3. Drug: FTC
  4. Drug: FTC/TDF
  5. Drug: 3TC
  6. Drug: Third agent
MeSH:Infection

- Plasma HIV-1 RNA level < 50 copies/mL at screening visit - Adequate renal function - Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula (eGFRCG) and are on ARVs that are appropriately dose adjusted for renal function per package insert - All documented historical plasma genotype(s) must not show resistance to TDF or FTC, including, but not limited to the presence of reverse transcriptase resistance mutations K65R, K70E, M184V/I, or thymidine analog-associated mutations (TAMs) that include M41L, L210W, D67N, K70R, T215Y/F, K219Q/E/N/R. --- K65R ---

Primary Outcomes

Measure: Percent Change From Baseline to Week 48 in Spine BMD

Time: Baseline; Week 48

Measure: Percent Change From Baseline to Week 48 in Hip BMD

Time: Baseline; Week 48

Secondary Outcomes

Measure: Percent Change From Baseline to Week 24 in Spine BMD

Time: Baseline; Week 24

Measure: Percent Change From Baseline to Week 24 in Hip BMD

Time: Baseline; Week 24

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm

Time: Week 48

Measure: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline; Week 24

Measure: Change in Baseline in CD4+ Cell Count at Week 48

Time: Baseline; Week 48

48 A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults

The primary objective of this study is to evaluate the efficacy of switching to a fixed-dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing on a regimen consisting of boosted atazanavir (ATV) or darunavir (DRV) plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) in HIV-1 infected adults who are virologically suppressed.

NCT02603107
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: RTV
  2. Drug: ATV
  3. Drug: DRV
  4. Drug: COBI
  5. Drug: ATV/co
  6. Drug: DRV/co
  7. Drug: FTC/TDF
  8. Drug: ABC/3TC
  9. Drug: B/F/TAF

(If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL [e.g., < 20 copies/mL], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests) - Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I - No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) Key Exclusion Criteria: - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening - Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) - Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine based therapies) - Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance - A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. --- K65R ---

Primary Outcomes

Description: The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm

Time: Week 48

Secondary Outcomes

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm

Time: Week 48

Measure: Change From Baseline in CD4 Cell Count at Week 48

Time: Baseline to Week 48

49 A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Abacavir/Lamivudine (ABC/3TC) Plus a Third Antiretroviral Agent to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed HIV 1 Infected Adult Subjects

The primary objective of this study is to evaluate the efficacy of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) relative to continuing on a baseline regimen consisting of abacavir/lamivudine (ABC/3TC) plus a 3rd antiretroviral agent in HIV-1 infected participants.

NCT02605954
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: E/C/F/TAF
  2. Drug: ABC/3TC
  3. Drug: Third Antiretroviral Agent
MeSH:Infection

- All documented historical plasma genotype(s) must not show resistance to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC), including, but not limited to the presence of reverse transcriptase resistance mutants K65R, K70E, M184V/I, or thymidine analog associated mutations (TAMs) (TAMs are: M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). --- K65R ---

Primary Outcomes

Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24

Time: Week 24

Secondary Outcomes

Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 12 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12

Time: Week 12

Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 48

Time: Week 48

Measure: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline; Week 24

Measure: Change From Baseline in CD4+ Cell Count at Week 48

Time: Baseline; Week 48

50 Efficacy, Safety and Tolerability of Switching to Dolutegravir/Lamivudine in Virologically-suppressed Adults Living With HIV on Bictegravir/Tenofovir Alafenamide/emtricitabine-the DYAD Study

Phase 4, randomized, open-label study to evaluate the efficacy, safety and tolerability of switching virologically suppressed adults living with HIV on bictegravir/tenofovir alafenamide/emtricitabine to dolutegravir/lamivudine

NCT04585737
Conditions
  1. HIV I Infection
Interventions
  1. Drug: Dolutegravir / Lamivudine Pill
  2. Drug: Bictegravir / Emtricitabine / Tenofovir Alafenamide Pill

Any evidence of major NRTI mutation (defined as history of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), M184V/I, T69-insertions, or K65R/E/N) or presence of any major INSTI resistance-associated mutation [17] in any available prior resistance genotype assay test result 16. --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215F --- --- K219Q --- --- M184V --- --- K65R ---

Primary Outcomes

Description: percentage with HIV-1 RNA ≥50 copies/mL at Week 48 in each treatment arm

Measure: The Primary outcome measure is to evaluate the efficacy of switching from B/F/TAF to DTG/3TC versus continuing B/F/TAF as determined by the proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48

Time: 48 weeks

Secondary Outcomes

Description: percentage with HIV-1 RNA ≥50 copies/mL at Weeks 12 and 24 in each treatment arm

Measure: The Secondary outcome measure is to evaluate the efficacy of switching to DTG/3TC from B/F/TAF as determined by the proportion of participants with HIV-1 RNA≥ 50 copies/mL at Weeks 12 and 24

Time: 12 and 24 weeks

Description: percentage with HIV-1 RNA<50 copies/mL at Weeks 12, 24 and 48 in each treatment arm

Measure: The secondary outcome measure is to evaluate the efficacy of switching to DTG/3TC from B/F/TAF as determined by the proportion of participants with HIV-1 RNA<50 copies/mL at Weeks 12, 24 and 48

Time: 12, 24 and 48 weeks

Description: AEs and lab abnormalities graded using DAIDS grading scale

Measure: The secondary outcome measure is to measure the Incidence and severity of adverse events and laboratory abnormalities (graded using DAIDs grading scale) through 48 weeks

Time: 48 weeks

Description: Number of participants who discontinue study treatment and reasons for discontinuation

Measure: The secondary outcome measure is to evaluate the proportion of participants that discontinue treatment through 48 weeks in each treatment arm and reasons for discontinuation

Time: 48 weeks

Description: Change from Baseline in fasting lipids at Weeks 24, and 48

Measure: The secondary outcome measure is to evaluate the effects of DTG/3TC once daily on fasting lipids over time compared to B/F/TAF through 48 weeks

Time: 48 weeks

Description: Change from Baseline in weight (kg) measured at Weeks 12, 24, and 48

Measure: The secondary outcome measure is to evaluate changes in weight (kg) in those treated with DTG/3TC vs. B/F/TAF over time

Time: 12, 24 and 48 weeks

Description: Change from Baseline in waist circumference (measured in inches) at Weeks 12, 24, and 48

Measure: The secondary outcome measure is to evaluate changes in waist circumference (inches) in those treated with DTG/3TC vs. B/F/TAF over time

Time: 12, 24 and 48 weeks

Description: Change from Baseline in weight (kg) and height (meters) will be used to assess changes in BMI (kg/m2) measured at Weeks 12, 24, and 48

Measure: The secondary outcome measure is to evaluate changes in BMI (kg/m2) in those treated with DTG/3TC vs. B/F/TAF over time

Time: 12, 24 and 48 weeks

Description: Change from Baseline in health status using the HIV-Symptoms Index questionnaire (validated 20-item questionnaire which asks subjects to rate the degree of bother they experience for each symptom in the past two weeks, the rating scale for each item ranges from 0-4 with higher values indicating greater symptom distress). This questionnaire will be administered on paper at Weeks 4, 12, 24 and 48 (or Withdrawal from the study)

Measure: The secondary outcome measure is to assess health related quality of life for subjects treated with DTG/3TC compared to B/F/TAF over time using the HIV-Symptoms Index questionnaire

Time: 4, 12, 24 and 48 weeks (or at study withdrawal)

Description: Change from baseline in treatment satisfaction using the HIV Treatment Satisfaction Questionnaire (validated 10-item questionnaire which asks subjects to rate how satisfied they are with different aspects of their HIV treatment, each item utilizes a rating scale of 0-6 with higher numbers indicating greater satisfaction). This survey will be administered on paper at Weeks 4, and 24 (or withdrawal from the study)

Measure: To assess treatment satisfaction in subjects treated with DTG/3TC compared to B/F/TAF over time using the HIV-Treatment Satisfaction Questionnaire

Time: 4 and 24 weeks (or at study withdrawal)

Description: to measure the incidence of observed genotypic resistance to ARVs for subjects meeting Virologic Rebound Criteria

Measure: To assess the number of subjects with genotypic mutations affecting any component of the treatment regimen among subjects meeting Virologic Rebound Criteria (HIV-1 RNA≥50 copies/mL X2) using HIV genotypic and ARCHIVE HIV-DNA testing

Time: 48 weeks

51 A Pilot Study of Highly Active Antiretroviral Therapy Using Isentress (Raltegravir) and Epzicom (Abacavir/Lamivudine) in Antiretroviral Naive HIV-Infected Subjects

To evaluate the efficacy and safety of Raltegravir and Epzicom over 48 weeks in ART-naive HIV-infected subjects.

NCT00740064
Conditions
  1. HIV Infections
Interventions
  1. Drug: Raltegravir and Abacavir/Lamivudine
MeSH:HIV Infections

Exclusion Criteria: - Screening HIV-1 genotype indicating the presence of any of the following mutations: K65R, L74V, and Y115F or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, associated with ABC and 3TC resistance, and mutations Q148H/R/K and N155H associated with RTG resistance. --- K65R ---

Primary Outcomes

Measure: To evaluate the efficacy and safety of RTG and ABC/3TC over 48 weeks in ART-naive HIV-infected subjects.

Time: 48 weeks

Secondary Outcomes

Measure: To assess the immunologic response, changes in fasting lipids, renal function, and development of resistance of the study regimen

Time: 48 weeks

52 A Phase 4, Randomized, Open Label, Controlled Study of Boosted Darunavir and Lamivudine Versus Boosted Darunavir and Emtricitabine/Tenofovir or Lamivudine/Tenofovir in Naïve HIV-1 Infected Subjects

The purpose of this study is to compare the safety and efficacy of a combination of a QD regimen consisting on ritonavir boosted darunavir (FDC) and lamivudine versus ritonavir boosted darunavir (FDC) plus co-formulated tenofovir and emtricitabine or co-formulated tenofovir/lamivudine in naïve HIV-1 infected patients. Subjects will be ARV-naïve HIV-1-infected patients eligible to start ARV therapy according to current guidelines.Subjects will be adults ≥ 18 years of age who meet all of the inclusion criteria and none of the exclusion criteria.

NCT02770508
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: darunavir/ritonavir
  2. Drug: Lamivudine
  3. Drug: emtricitabine-tenofovir(FTC/TDF)

- Any of the following mutations will be considered resistance to 3TC or FTC : M184V/I and /or K65R and / or Q151M. --- M184V --- --- K65R ---

- Any of the following mutations will be considered resistance to TDF: K65R, K70E, double insertion 69 or 3 TAMS including M41L or L210W. --- K65R ---

Primary Outcomes

Description: The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) <50 c/mL at Week 48 will be assessed using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks).

Measure: Percentage of patients with HIV-1 RNA levels of less than 50 copies/mL at week 48

Time: 48 weeks

Secondary Outcomes

Description: The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) <400 c/mL at Week 24 will be assessed using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm.

Measure: Percentage of patients with HIV-1 RNA <400 copies/mL at week 24

Time: 24 weeks

Description: An genotiping test will be made at time to virological failure to detect mutation across reverse transcriptase (RT), and Protease (PRO). Protocol defined virological failure was defined as confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 or confirmed plasma HIV-1 RNA levels >=50 copies/mL at week 48

Measure: Number and type of resistance mutations in case of virologic failure

Time: from week 24 to week 48

Description: Change from Baseline in CD4+ cell counts will be assessed at Weeks 24 and 48.

Measure: CD4+ lymphocyte count and change between baseline (defined as the average between screening and baseline visit values) and weeks 24 and 48

Time: week 24 and 48

Description: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

Measure: Frequency, type and severity of adverse events and laboratory abnormalities.

Time: week 24 and 48

Description: Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline (BS) to a CDC CAT C event (EV); CDC CAT B at BS to a CDC CAT C EV; CDC CAT C at BS to a new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.

Measure: Clinical disease progression (CDP)

Time: week 24 and 48

Description: The evaluation of quality of life will be done through two validated instruments: the Medical Outcomes Study HIV Health Survey ( MOS - HIV) and EuroQol 5D (EQ - 5D ) . Both instruments will be administered to patients at baseline , week 24 and week 48 .

Measure: Changes in quality of life

Time: baseline, week 24 and week 48

53 A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) Fixed Dose Combination (FDC) in HIV-1 Infected Adolescents and Children

Cohort 1 and 2: The primary objectives of this study are: Part A: - To evaluate the steady state pharmacokinetics (PK) of bictegravir (BIC) and confirm the dose of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in HIV-1 infected, virologically suppressed adolescents (12 to < 18 years of age) and children (6 to < 12 years of age) Parts A and B: - To evaluate the safety and tolerability of the adult strength B/F/TAF FDC through Week 24 in HIV-1 infected, virologically suppressed adolescents (12 to <18 years of age) and children (6 to <12 years of age) Cohort 3: The primary objectives of this study are: Part A: - To evaluate the steady state PK of BIC and confirm the dose of B/F/TAF 30/120/15 mg FDC in HIV-1 infected, virologically suppressed children ≥ 2 years of age weighing ≥ 14 to < 25 kg Parts A and B: - To evaluate the safety and tolerability of the low dose B/F/TAF FDC tablet through Week 24 in HIV-1 infected, virologically suppressed children ≥ 2 years of age weighing ≥ 14 to < 25 kg Cohort 4: Group 1: The primary objective of this study is: - To evaluate the safety and tolerability of B/F/TAF 30/120/15 mg FDC TOS (administration of 2 B/F/TAF 15/60/7.5 mg FDC tablets for oral suspension (TOS)) through Week 24 in HIV-1 infected, virologically suppressed children ≥ 2 years of age weighing ≥ 14 to < 25 kg who are unable to swallow tablets Group 2: The primary objectives of this study are: - To evaluate the steady state PK of BIC and TAF and confirm the dose of B/F/TAF 15/60/7.5 mg FDC TOS in HIV-1 infected children ≥ 1 month of age, on antiretroviral (ARV) treatment or treatment naive, weighing ≥ 10 to < 14 kg - To evaluate the safety and tolerability of the B/F/TAF 15/60/7.5 mg FDC TOS through Week 24 in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 10 to < 14 kg Group 3: The primary objectives of this study are: - To evaluate the steady state PK of BIC and TAF and confirm the dose of B/F/TAF 7.5/30/3.75 mg FDC TOS (administration of 2 B/F/TAF 3.75/15/1.88 mg FDC TOS) in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 6 to < 10 kg - To evaluate the safety and tolerability of B/F/TAF 7.5/30/3.75 mg FDC TOS (administration of 2 B/F/TAF 3.75/15/1.88 mg FDC TOS) through Week 24 in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 6 to < 10 kg Group 4: The primary objectives of this study are: - To evaluate the steady state PK of BIC and TAF and confirm the dose of B/F/TAF 3.75/15/1.88 mg FDC TOS in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 3 to < 6 kg - To evaluate the safety and tolerability of the B/F/TAF 3.75/15/1.88 mg FDC TOS through Week 24 in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 3 to < 6 kg

NCT02881320
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: B/F/TAF (Adult Strength)
  2. Drug: B/F/TAF (Low Dose)
  3. Drug: B/F/TAF (TOS)
  4. Drug: B/F/TAF (TOS)
  5. Drug: B/F/TAF (TOS)
  6. Drug: B/F/TAF (TOS)

m^2 according to the Schwartz Formula - No documented or suspected resistance to emtricitabine (FTC), tenofovir (TFV), or integrase strand transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R and M184V/I Cohort 4 Group 2-4: HIV-1 infected children (≥ 1 month of age and screening weight of ≥ 3 to < 14 kg) who are treatment naive or on ARV treatment for ≥ 1 month prior to screening - Positive confirmatory HIV test (confirmatory nucleic acid-based testing if < 18 months of age) - On a stable ARV regimen for ≥ 1 month or treatment naive (Individual is considered treatment naive if ARVs were given for prevention of mother-to-child transmission but not for HIV treatment) - For < 1 year of age, eGFR ≥ the minimum normal values for age according to the information below using the Schwartz Formula - 30 mL/min/1.73 --- K65R ---

m^2 using the Schwartz Formula - No documented or suspected resistance to FTC, TFV, or INSTIs including, but not limited to, the reverse transcriptase resistance mutation K65R. --- K65R ---

Primary Outcomes

Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: AUCtau of Bictegravir

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: Ctau is defined as the observed drug concentration at the end of the dosing interval. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Ctau of Bictegravir

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 24

Time: Up to 24 weeks

Measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24

Time: Up to 24 weeks

Description: AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: AUClast of TAF (Cohort 4)

Time: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: Cmax is defined as maximum observed concentration of drug. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Cmax of TAF (Cohort 4)

Time: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Secondary Outcomes

Measure: Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm

Time: Week 24

Measure: Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm

Time: Week 48

Measure: Change from Baseline in CD4+ Cell Counts at Week 24

Time: Week 24

Measure: Change from Baseline in CD4+ Cell Counts at Week 48

Time: Week 48

Measure: Change from Baseline in CD4+ Cell Count Percentages at Week 24

Time: Week 24

Measure: Change from Baseline in CD4+ Cell Count Percentages at Week 48

Time: Week 48

Description: Tmax is defined as the time (observed time point) of Cmax. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Tmax of Bictegravir

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: Cmax is defined as the maximum observed concentration of drug. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Cmax of Bictegravir

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: AUClast is defined as the area under the concentration of drug from time zero to the last observable concentration. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: AUClast of Bictegravir

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: T1/2 is defined as the estimate of the terminal elimination half-life of the drug. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: T1/2 of Bictegravir

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: CL is defined as the systemic clearance of the drug following study drug administration. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Apparent Clearance (CL) of Bictegravir

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: Vz is defined as the volume of distribution of the drug after study drug administration. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Apparent Vz of Bictegravir

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: AUCtau of TAF and FTC

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: AUClast is defined as the area under the concentration of drug from time zero to the last observable concentration. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose.

Measure: PK Parameter: AUClast of TAF and FTC (Cohorts 1, 2, and 3)

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose

Description: AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: AUClast of FTC (Cohorts 4)

Time: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: Cmax is defined as the maximum observed concentration of drug. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose.

Measure: PK Parameter: Cmax of TAF and FTC (Cohorts 1, 2, and 3)

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose

Description: Cmax is defined as maximum observed concentration of drug. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Cmax of FTC (Cohorts 4)

Time: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: Ctau is defined as the observed drug concentration at the end of the dosing interval. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Ctau of TAF and FTC

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: Tmax is defined as the time (observed time point) of Cmax. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Tmax of TAF and FTC

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: T1/2 is defined as the estimate of the terminal elimination half-life of the drug. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: T1/2 of TAF and FTC

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: CL is defined as the systemic clearance of the drug following study drug administration. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Apparent CL of TAF and FTC

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Description: Vz is defined as the volume of distribution of the drug after study drug administration. Cohorts 1 & 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

Measure: PK Parameter: Apparent Vz of TAF and FTC

Time: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

Measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events Through Week 48

Time: Up to 48 weeks

Measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 48

Time: Up to 48 weeks

Description: Participants or legal guardian will be asked: if study drug shape and size were acceptable (for Cohort 1 and Cohort 2) about ease of swallowability and the shape and size of study drug when swallowed (for Cohort 3) about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste (for Cohort 4)

Measure: Acceptability of B/F/TAF Formulation at Day 1 (All Cohorts)

Time: Day 1

Description: Participants or legal guardian will be asked about the study drug taste (All Cohorts)

Measure: Palatability of B/F/TAF Formulation at Day 1 (All Cohorts)

Time: Day 1

Description: Participants or legal guardian will be asked: if study drug shape and size were acceptable (for Cohort 1 and Cohort 2) about ease of swallowability and the shape and size of study drug when swallowed (for Cohort 3). about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste (for Cohort 4)

Measure: Acceptability of B/F/TAF Formulation at Week 4 (All Cohorts)

Time: Week 4

Description: Participants or legal guardian will be asked about the study drug taste (All Cohorts)

Measure: Palatability of B/F/TAF Formulation at Week 4 (All Cohorts)

Time: Week 4

Description: Participants or legal guardian will be asked: about ease of swallowability and the shape and size of study drug when swallowed (for Cohort 3). about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste (for Cohort 4)

Measure: Acceptability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4)

Time: Week 24

Description: Participants or legal guardian will be asked about the study drug taste

Measure: Palatability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4)

Time: Week 24

Description: Participants or legal guardian will be asked: about ease of swallowability and the shape and size of study drug when swallowed (for Cohort 3). about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste (for Cohort 4)

Measure: Acceptability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4)

Time: Week 48

Description: Participants or legal guardian will be asked about the study drug taste

Measure: Palatability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4)

Time: Week 48

Description: Participants or legal guardian will be asked about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste

Measure: Acceptability of B/F/TAF Formulation at Week 1 (Cohort 4)

Time: Week 1

Description: Participants or legal guardian will be asked about the study drug taste

Measure: Palatability of B/F/TAF Formulation at Week 1 (Cohort 4)

Time: Week 1

Description: Participants or legal guardian will be asked about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste

Measure: Acceptability of B/F/TAF Formulation at Week 2 (Cohort 4)

Time: Week 2

Description: Participants or legal guardian will be asked about the study drug taste

Measure: Palatability of B/F/TAF Formulation at Week 2 (Cohort 4)

Time: Week 2


HPO Nodes


HP:0004324: Increased body weight
Genes 585
NTRK2 BLK MERTK SH2B1 PROK2 FIBP MAGEL2 FEZF1 MEGF8 ALG13 MEN1 CUL4B MAGEL2 BBIP1 AGTR2 ZNF711 GTF2IRD1 SLC9A7 SLC7A14 RP1 OFD1 CEP164 PHF21A FRMPD4 BRAF RTL1 PHF6 BBS1 FGFR3 KCNJ11 CNNM2 GNAS PDE6A MTOR CNGB1 ARVCF HACE1 LIPE ZNF408 UCP2 HNF4A WDR11 CTNNB1 EIF2S3 RREB1 TOPORS IFT172 OCA2 IFT172 LZTFL1 KCNJ11 RBP3 RYR1 ERMARD ARX AP4B1 SAG TMEM43 PAX4 ATP10A CEP290 UBE3A NDN NDN SYNE1 BBS10 H6PD DMD RAB39B FLRT3 PROKR2 RTL1 PCNT SIM1 TTC8 CLIP2 ABCC8 ELN TBX3 IGF1R HIRA GP1BB GNAS DIS3L2 VPS13B OFD1 BAP1 EMD ADNP SEC24C ELN KLF11 TULP1 KIDINS220 GNAS THOC2 KIF7 PIGA RNPC3 GHR SNRNP200 CLCN4 P4HTM AKT2 AP4M1 IGSF1 PRMT7 IFT74 GDI1 NEUROD1 TRIP4 SIN3A RTL1 HESX1 PTCHD1 DLK1 C8ORF37 PDE4D WNT4 SUFU CREBBP NPAP1 PDE4D PIGT VPS13B SDC3 BBS4 SLC7A7 PTCH1 ARL6 RP9 IFT88 TMEM67 SLC10A7 RHO CD46 MYT1L BLM PDX1 NPHP1 ARL3 IFT27 RPGR MYF6 FGFR1 PDE6B DLK1 ATP6AP2 MEG3 MC3R ZNF365 HNF4A SNORD115-1 ZNF513 THRA SRY BBS10 SOX3 SPRY4 RLBP1 RAB23 MKRN3-AS1 TSPAN7 AP4E1 ACADVL PDSS1 FAM161A FTSJ1 ROM1 PCSK1 AP4S1 SNRPN TTC8 FGF17 ABCC8 MAPK8IP3 SH2B1 IGF1 ZNF81 HUWE1 IDH3B BBIP1 PDE4D USP8 CACNA1S EGF FHL1 USP8 BEST1 KMT2A GNAS PWRN1 TBX3 IPW RP2 WDPCP KMT2D XYLT1 BBS9 ARNT2 APPL1 SUFU CHD8 FGF8 PAK3 IMPDH1 SNRPN MEGF8 DHDDS EIF2S3 BAP1 GCK RAI1 MCM3AP SH2B1 HNF1A RPE65 SNRPN ZBTB20 SMARCB1 NKAP SPATA7 HDAC8 P2RY11 WT1 XRCC4 PRMT7 ARHGEF18 BBS9 ABCC8 POMC HLA-DQB1 HS6ST1 TRIM32 WT1 CREBBP CANT1 OCA2 NR0B2 UBE2A THOC2 LMNA KLHL7 STX16 SDCCAG8 RAD21 ALMS1 SEMA4A USH2A CERKL FMR1 TRAF7 CYP19A1 PAX6 TNFSF4 PTEN ODC1 FGFR1 BBS7 DDX6 AFF4 MAGEL2 ACSL4 CHD7 CCDC141 PCNT PRPF8 MID2 DNM2 GABRA3 BBS7 HNF1A KDM6A CDHR1 SNRPN HLA-DRB1 DYNC2I2 UBE3A TRIM32 MAGEL2 PWAR1 TRIP12 KCNJ11 EYS BRAF SYNE2 ARL6 SHOX TACR3 CNKSR2 CEP19 CLRN1 NIPBL SMAD4 NDN MTTP TCF20 USP9X MKRN3 ADRB3 SETD2 CFI OCA2 MRAP2 ENPP1 DHX38 IFT172 ADRB2 RTL1 CARTPT CUL4B SMO SNRPN PIGN DLK1 LEP CYP7A1 ARL2BP MAN1B1 PRCD IL1RAPL1 PRPH2 CDH23 NEK2 ODC1 NSMF NDN PIGL REEP6 JMJD1C CREBBP AGBL5 PDGFB PROM1 TBX1 MTFMT MECP2 MAN1B1 GNAS LEPR TBL2 POMC SIM1 TBX1 BBS2 PIGT HERC1 SDCCAG8 SPG11 EHMT1 IFT140 PNKP MTOR MEG3 FOXP1 PSMD12 RFC2 TMCO1 GATA4 SNORD116-1 LEPR MKKS LMNA LIMK1 BLK MED12 BBS12 MKS1 PCSK1 SMARCE1 ABCA4 IDH3A EP300 BBS1 KIZ ATRX BBS5 BDNF TRAPPC9 IMPG2 HESX1 MKS1 PDE11A SIN3A SOX10 MAGEL2 SYP RPS6KA3 TBX1 ZNF41 KISS1R MEG3 STEEP1 IQSEC2 TRAF3IP1 TUB TAF1 ATRX PRDM16 UBE3A CFH C8ORF37 DEAF1 LEP AFF4 UBE3A RAB23 DNMT3A COA3 RTL1 USP27X IQSEC2 GHRL BPTF LAS1L INS RAI1 ARL13B PHIP EXOC6B MECP2 SNRPN RERE OTX2 RBMX SIM1 PNPLA6 SKI WAC DPYD POGZ DCC IL17RD FIBP POMGNT1 PDE6G GLI3 HDAC4 SLC25A4 ALMS1 POU3F4 AKT2 PAX6 CCDC141 TRAPPC9 SEMA3A AHI1 MC4R HACE1 TERT BBS2 PKDCC PIK3CA GABRD TP53 ARMC5 RP1L1 EHMT1 CRB1 CNGA1 EHMT1 ANOS1 NF2 ABCC9 ANK3 LARS2 UFD1 HGSNAT SH3KBP1 HNF4A ARMC5 UCP3 CCDC28B GTF2I MAGEL2 HSD11B1 SHANK3 BBS5 PRPF3 GUCA1B INPP5E PPARG IGFALS FTO GNAS SETD5 ARL6 BBS4 RAI1 XYLT1 TTC8 NR2E3 PCARE IFT172 MAK MEG3 ADCY3 RNF135 UPF3B SMC1A NDN PROK2 SOX2 DUSP6 POMC HCFC1 COL10A1 MKKS SMC3 FSCN2 ADNP GNAS-AS1 CA4 ALB MC4R PRKACA NIN SNRPN IFT27 AKT1 RGR AHR PRPF4 MOG HDAC8 HERC2 ZNF711 TUB NDNF LRAT CEP290 DLG3 MTMR14 DYRK1B SCAPER CRX EP300 DLK1 KIAA1549 KCNJ18 MAGEL2 PROKR2 MLXIPL KIDINS220 MEG3 FXR1 LZTFL1 BBS12 PRPF31 IQSEC2 KMT2C PRPF6 AGRP ATP7B HCRT BBS2 DLK1 MOG APOE BIN1 HELLPAR GNAS NRL PRKAR1A BAZ1B LAS1L RDH12 ARL6 COMT HDAC8 USP7 FLII ARHGEF6 FOXP1 AIP KCNAB2 C8ORF37 PHF6 GNAS RPS6KA3 PRKAR1A EDNRB CTSH CEL OCA2