SNPMiner Trials by Shray Alag

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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation V82A

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

There are 16 clinical trials

Clinical Trials


1 A Pilot Trial Evaluating Maintenance Therapy With Lamivudine(Epivir®) and Dolutegravir(Tivicay®) in Human Immunodeficiency Virus 1 (HIV-1) Infected Patients Virologically Suppressed With Triple HAART - ANRS 167 Lamidol

The principal objective is to evaluate the antiviral efficacy of 48 weeks treatment with the two-drugs combination dolutegravir(Tivicay®) and lamivudine(TEpivir®) in HIV-1 infected patients virologically suppressed with triple HAART.

NCT02527096
Conditions
  1. HIV-1 Infection
Interventions
  1. Drug: dolutegravir (Tivicay®) - Phase 1
  2. Drug: lamivudine (Epivir®) - Phase 2
  3. Drug: dolutegravir (Tivicay®) - Phase 2
MeSH:Acquired Immunodeficiency Syndrome HIV Infections

Inclusion Criteria: - HIV-1 infected patient - Age ≥ 18 years - CD4 cell count nadir > 200/mm3 - Genotype on pre-HAART interpreted with the last version of the ANRS AC11 resistance group's algorithm which presents: - no major mutation on protease among: D30N, V32I, M46I/L, I47A/V, G48V, I50L/V, 154M/L, L76V, V82A/F/T/S, I84V, N88D/S, L90M,- no mutation on RT (except the mutation A98S if the patient is not infected by the virus subtype C), - no mutation on integrase (if the genotype is available), - First-line treatment with suppressive triple HAART (2 NRTI + either 1 PI/r, 1 NNRTI or 1 INI). --- D30N --- --- V32I --- --- M46I --- --- I47A --- --- G48V --- --- I50L --- --- L76V --- --- V82A ---

Primary Outcomes

Description: Virological failure is defined by plasma HIV RNA > 50 cp/mL on 2 following samples at 2 to 4 weeks apart.

Measure: Virological success without any intercurrent event leading to interrupt the strategy of the trial (analysis)

Time: from week 8 to week 56 (± 4 weeks)

Secondary Outcomes

Description: Evaluation was calculated as the CD4 count at the corresponding week minus the baseline CD4 count

Measure: Evolution of CD4 and CD8 lymphocytes count (analysis)

Time: from week 8 to week 32 and week 56

Measure: Percentage of participants who discontinued the strategy of the trial for toxicity or with adverse event of grade 3 or 4 (analysis)

Time: week 56

Measure: Profile of resistance mutations in plasma in case of virological failure

Time: week 56

Measure: Percentage of participants with plasma HIV RNA < 1 cp/mL

Time: Day 0, week 8, week 32 and week 56

Description: Influence of total DNA at Day 0 on the occurrence of virological failure or blip

Measure: Influence of total DNA on the occurrence of virological failure or blip

Time: from Day 0 to week 56

Measure: Measure of concentrations of dolutegravir(Tivicay®) and lamivudine(Epivir®) in case of virological failure or with a blip

Time: week 56

Measure: Measure of adherence to treatment (self-reported)

Time: Day 0, week 4, week 8, week 32 and week 56

Measure: Measure of quality of life (self-reported)

Time: Day 0, week 8 and week 56

Description: Evaluation of medico-economic aspects. Evaluate the direct medical cost related to dolutegravir and lamivudine versus the cost of the previous treatment.

Measure: Comparison of Medico-economic substudy (analysis)

Time: week 56

Description: Measure of concentrations of dolutegravir and NRTI, and HIV RNA in semen at Week 8 and Week 32 in a subgroup of 20 participants

Measure: Sperm substudy measure of concentration

Time: Week 8 and week 32

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 --- --- D67N --- --- K70R --- --- K70E --- --- L74V --- --- Y115F --- --- M184V --- --- M184V --- --- L210W --- --- T215Y --- --- K219Q --- --- L100I --- --- K103N --- --- V106M --- --- V106A --- --- V108I --- --- Y181C --- --- Y181C --- --- Y188L --- --- Y188C --- --- G190S --- --- G190A --- --- P225H --- --- D30N --- --- V32I --- --- L33F --- --- M46I --- --- I47V --- --- G48V --- --- I50L --- --- I50V --- --- I54M --- --- L76V --- --- V82A ---

- 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 --- --- D67N --- --- K70R --- --- K70E --- --- L74V --- --- Y115F --- --- M184V --- --- M184V --- --- L210W --- --- T215Y --- --- K219Q --- --- L100I --- --- K103N --- --- V106M --- --- V106A --- --- V108I --- --- Y181C --- --- Y181C --- --- Y188L --- --- Y188C --- --- G190S --- --- G190A --- --- P225H --- --- D30N --- --- V32I --- --- L33F --- --- M46I --- --- I47V --- --- G48V --- --- I50L --- --- I50V --- --- I54M --- --- L76V --- --- V82A --- --- V82A ---

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 --- --- L33I --- --- V82A ---

Primary Outcomes

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

Time: 48 weeks

4 Prospective Clinical Trial to Assess Safety and Efficacy of DRV/r(TMC 114/r), ETV(TMC 125) and MK-0518 in Addition to OBT in HIV-1 Infected Patients With Limited to No Treatment Options ANRS 139 TRIO

The purpose of this study is to look at the safety and efficacy of a combination of 3 new antiretroviral drugs: darunavir, etravirine and MK-0518 (raltegravir) in patients who have multi-resistant viruses and limited treatment options. An optimized background regimen that may include nucleoside reverse transcriptase inhibitors (NRTIs) and enfuvirtide can be added, if possible, to this combination. Patients will undergo treatment for 48 weeks and virological efficacy will be evaluated at week 24.

NCT00460382
Conditions
  1. HIV Infections
Interventions
  1. Drug: raltegravir potassium
  2. Drug: darunavir/ritonavir
  3. Drug: etravirine
  4. Drug: Optimized background regimen
MeSH:HIV Infections

- Genotypic resistance testing at the screening visit: - Protease inhibitor mutations: over or equal to 3 primary protease inhibitor mutations among: D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54M, L76V, V82A/F/L/T/S, I84V, N88S and L90M (IAS list 2006) but below or equal to 3 mutations among the following: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V et L89V (virus sensitivity to darunavir/ritonavir). - Reverse transcriptase mutations: over or equal to 3 NRTI mutations (among IAS list) and below or equal to 3 mutations among: A98G, L100I, K101Q/P/E, K103H/N/S/T, V106A/M, V108I, E138G/K/Q, V179D/E/F/G/I, Y181C/I/V/C/H/L, Y188C/H/L, G190A/C/E/Q/S, P225H, F227C/L, M230I/L, P236L, K238N/T and Y318F (virus sensitivity to etravirine) Exclusion Criteria: - Non effective barrier contraception in women of child bearing potential - Pregnant women or women who are breastfeeding - Opportunistic infection at the acute phase - Decompensated cirrhosis (stage B or C of Child-Pugh score) - Malignancy requiring chemotherapy or radiotherapy - Contraindicated medications being taken by the patient (listed in protocol) - Allergy to the active substances and expedients of darunavir, etravirine and raltegravir. --- D30N --- --- V32I --- --- L33F --- --- M46I --- --- I47A --- --- G48V --- --- I50L --- --- I54M --- --- L76V --- --- V82A ---

Primary Outcomes

Measure: Proportion of patients with HIV RNA levels of less than 50 copies/ml in an intent to treat analysis at week 24

Time: week 24

Secondary Outcomes

Measure: Proportions of patients with HIV RNA levels of less than 50 copies/ml at week 48, with HIV RNA levels of less than 400 copies/ml at weeks 24 and 48

Time: week 24 and 48

Measure: HIV RNA level evolution between baseline and week 48

Time: from week 0 to 48

Measure: HIV proviral DNA and 2LTR circle HIV DNA between baseline and week 48

Time: from week 0 to 48

Measure: Number and type of resistance mutations in case of virologic failure occurrence

Time: from week 0 to 48

Measure: CD4 lymphocyte count and proportion evolution between baseline and week 48

Time: from week 0 to 48

Measure: HIV infection progression

Time: from week 0 to 48

Measure: Frequency of the study regimen modifications and interruption

Time: from week 0 to 48

Measure: Study regimen tolerance

Time: from week 0 to 48

Measure: Study regimen adherence

Time: from week 0 to 48

Measure: Association between study drugs' minimum concentrations at week 4 and week 12 and virologic success at week 24

Time: from week 4 to 24

Measure: Evolution of pharmacokinetics parameters of study drugs in the PK substudy

Time: betwwen week 1 and 4

5 Prevention of HIV1 Mother to Child Transmission Without Nucleoside Analogue Reverse Transcriptase Inhibitors in the Pre-partum Phase. A Multicenter Randomised Phase II/III Open Label Study With a Group of 100 Pregnant Women Receiving Lopinavir/Ritonavir and a Group of 50 Receiving Lopinavir/Ritonavir Plus Zidovudine and Lamivudine. ANRS 135 Primeva

In the pre-partum phase the use of antiretroviral therapy for the mother during the last trimester of pregnancy is mandatory. The use of HAART during pregnancy, usually two nucleosides analogues and a protease inhibitor exposes the mother and the child to cumulate toxicities related to both families. The aim of this study is to assess the use of a boosted protease inhibitor without nucleoside analogue during the pre-partum phase for women with no indication of antiretroviral therapy for their own.

NCT00424814
Conditions
  1. HIV Infections
Interventions
  1. Drug: Kaletra (lopinavir/ritonavir)
  2. Drug: Kaletra (lopinavir/ritonavir) + Combivir (zidovudine/lamivudine)
MeSH:HIV Infections

Inclusion Criteria: Assessed between 20 and 24 months of pregnancy - Pregnancy known before 24 weeks of gestation - Documented HIV-1 infection without indication for ARV therapy - CD4 count above or equal to 350 per mm3 - VL under 30 000 copies per ml - Naïve for PI (except treatment during previous pregnancy) - Informed consent signed Exclusion Criteria: - HIV2 infection or HIV1 group O infection - Any pathology related to pregnancy - Contra-indication to study drugs - Unstable hypertension or diabetes - Known risk of premature delivery - In case of previous treatment with a protease inhibitor : presence of resistance mutations on the HIV-1 protease gene by genotyping analysis (1 mutation among V32I et I47A, I50V V82A/F/S/T, I84V, L90 M or more than 3 mutations among L10 F/I/R/V, K20/M/R, L24I, L33F, M46I/L, F53L, I54M/L/T/V, L63P, A71L/V/T,) Inclusion Criteria: Assessed between 20 and 24 months of pregnancy - Pregnancy known before 24 weeks of gestation - Documented HIV-1 infection without indication for ARV therapy - CD4 count above or equal to 350 per mm3 - VL under 30 000 copies per ml - Naïve for PI (except treatment during previous pregnancy) - Informed consent signed Exclusion Criteria: - HIV2 infection or HIV1 group O infection - Any pathology related to pregnancy - Contra-indication to study drugs - Unstable hypertension or diabetes - Known risk of premature delivery - In case of previous treatment with a protease inhibitor : presence of resistance mutations on the HIV-1 protease gene by genotyping analysis (1 mutation among V32I et I47A, I50V V82A/F/S/T, I84V, L90 M or more than 3 mutations among L10 F/I/R/V, K20/M/R, L24I, L33F, M46I/L, F53L, I54M/L/T/V, L63P, A71L/V/T,) HIV Infections HIV Infections Recent data from the French perinatal cohort and others indicate that HIV-RNA levels at delivery correlate with risk of transmission among women treated with antiretroviral agents. --- V32I --- --- I47A --- --- I50V --- --- V82A ---

Inclusion Criteria: Assessed between 20 and 24 months of pregnancy - Pregnancy known before 24 weeks of gestation - Documented HIV-1 infection without indication for ARV therapy - CD4 count above or equal to 350 per mm3 - VL under 30 000 copies per ml - Naïve for PI (except treatment during previous pregnancy) - Informed consent signed Exclusion Criteria: - HIV2 infection or HIV1 group O infection - Any pathology related to pregnancy - Contra-indication to study drugs - Unstable hypertension or diabetes - Known risk of premature delivery - In case of previous treatment with a protease inhibitor : presence of resistance mutations on the HIV-1 protease gene by genotyping analysis (1 mutation among V32I et I47A, I50V V82A/F/S/T, I84V, L90 M or more than 3 mutations among L10 F/I/R/V, K20/M/R, L24I, L33F, M46I/L, F53L, I54M/L/T/V, L63P, A71L/V/T,) Inclusion Criteria: Assessed between 20 and 24 months of pregnancy - Pregnancy known before 24 weeks of gestation - Documented HIV-1 infection without indication for ARV therapy - CD4 count above or equal to 350 per mm3 - VL under 30 000 copies per ml - Naïve for PI (except treatment during previous pregnancy) - Informed consent signed Exclusion Criteria: - HIV2 infection or HIV1 group O infection - Any pathology related to pregnancy - Contra-indication to study drugs - Unstable hypertension or diabetes - Known risk of premature delivery - In case of previous treatment with a protease inhibitor : presence of resistance mutations on the HIV-1 protease gene by genotyping analysis (1 mutation among V32I et I47A, I50V V82A/F/S/T, I84V, L90 M or more than 3 mutations among L10 F/I/R/V, K20/M/R, L24I, L33F, M46I/L, F53L, I54M/L/T/V, L63P, A71L/V/T,) HIV Infections HIV Infections Recent data from the French perinatal cohort and others indicate that HIV-RNA levels at delivery correlate with risk of transmission among women treated with antiretroviral agents. --- V32I --- --- I47A --- --- I50V --- --- V82A --- --- I84V --- --- L24I --- --- L33F --- --- M46I --- --- F53L --- --- I54M --- --- L63P --- --- A71L --- --- V32I --- --- I47A --- --- I50V --- --- V82A ---

Primary Outcomes

Measure: Proportion of mother with plasma HIV1 below 200 copies per ml after 8 weeks of treatment

Time: W8

Secondary Outcomes

Measure: Proportion of women maintained with monotherapy until delivery,

Time: delivery

Measure: Proportion of women with a VL below 50 copies per ml at delivery

Time: delivery

Measure: Proportion of women harbouring resistant HIV strains four weeks after delivery

Time: W4 post partum

Measure: Concentrations of studied drug in plasma and in cord-blood

Time: at delivery

Measure: HIV-1 detection and concentrations of studied drug in vaginal secretion before and after treatment

Time: W0, W8 of treatment

Measure: concentrations of studied drugs in the new born gastric fluid, HIV diagnostic in infant (criteria for stopping the trial at second infection)

Time: birth

6 A 24-week, Randomized, Open-label, 2-arm Study to Compare the Safety, Efficacy and Tolerability of Invirase® Tablets With Ritonavir Versus Kaletra® Tablets in HIV 1 Infected Adults on a Kaletra® Based Regimen With 2 Nucleosides/Nucleotides

This study will compare the benefit for patients switching from Kaletra® to Invirase® tablets over remaining on Kaletra® (based on randomization), to elicit the lipid benefits inferred in previous studies

NCT00438152
Conditions
  1. HIV Infections
Interventions
  1. Drug: Saquinavir (Invirase®)
  2. Drug: Lopinavir/ritonavir (Kaletra®)
MeSH:HIV Infections

- Ability and willingness to provide written informed consent and adhere to the study regimen - Females of childbearing potential must have a documented negative serum or urine pregnancy test at screening/baseline and ensure that 2 reliable forms of contraception are being used, including a barrier method, for the duration of the study and for 90 days after the last dose of study medication Exclusion Criteria: - Documented virological failure on a protease inhibitor ARV regimen prior to commencing Kaletra® regimen - Documented protease mutation (one or more from the following list) prior to commencing Kaletra® regimen: - M46I/L/V, I47A/V, G48V/M, I50V, F53L/Y, I54L/M/V/A/T/S, V82A/T/S/F/M/L, I84A/V/C, L90M - Patients with acute hepatitis B or C infection - Females who are pregnant, breast-feeding, or who plan to become pregnant or breast-feed during the study· - Significant renal dysfunction (creatinine clearance [CrCl] <60 mL/min) and/or hepatic impairment (aspartate aminotransferase/alanine aminotransferase [AST/ALT] >3 X ULN and/or documented liver cirrhosis) Note: The site will calculate each patient's CrCl using the Cockcroft-Gault formula [28] as shown below: CrCl = [140 - age (yr)] × weight (kg) × constant 72 × serum creatinine (Cr) (mg/dL) where, constant = 1 for men and 0.85 for women - Any current known clinical or laboratory parameter of ACTG Grade 4 (see Appendix 4). --- M46I --- --- I47A --- --- G48V --- --- I50V --- --- F53L --- --- I54L --- --- V82A ---

Primary Outcomes

Measure: To evaluate the lipid benefits of Invirase® tablets with ritonavir versus Kaletra® tablets in HIV-1 infected adults on an antiretroviral regimen containing Kaletra® with two nucleosides/nucleotides

Time: 24 weeks

Secondary Outcomes

Measure: To evaluate the efficacy of Invirase® tablets with ritonavir versus Kaletra® tablets in HIV-1 infected adults on an ARV regimen containing Kaletra® with 2 nucleosides/nucleotides.

Time: 4 weeks, 12 weeks and 24 weeks.

Measure: To evaluate additional safety and tolerability of Invirase® tablets with ritonavir versus Kaletra® tablets in HIV-1 infected adults on an antiretroviral regimen containing Kaletra® with 2 nucleosides/nucleotides.

Time: Week 24

7 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 ---

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

8 A 24 Week Phase IIIb/IV Single Arm Open Label Observational Study to Explore the Efficacy of Protease Inhibitors Given in Combination With Reverse Transcriptase Inhibitors to HIV-1 Infected Subjects With Protease Mutations Selected During Therapy With GW433908 Containing Antiretroviral Therapy

This study will assess the efficacy of subsequent protease inhibitor (PI)-containing therapy in subjects who have acquired HIV-1 protease mutations whilst receiving a GW433908 (fosamprenavir)-containing regimen.

NCT00242840
Conditions
  1. Infection, Human Immunodeficiency Virus I
  2. HIV Infection
Interventions
  1. Drug: No intervention; Observational study
MeSH:Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome

Exclusion criteria: - Have 2 or more of the primary resistance mutations D30N, G48V, V82A/F/T/S and L90M. --- D30N --- --- G48V --- --- V82A ---


9 A Phase 3, Randomized, Open-Label Study of Lopinavir/Ritonavir (LPV/r) Tablets 800/200 Milligram (mg) Once-Daily (QD) Versus 400/100 mg Twice-Daily (BID) When Coadministered With Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) in Antiretroviral-Experienced, Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects

The purpose of this study was to compare the safety, tolerability, and antiviral activity of once-daily (QD) and twice-daily (BID) dosing of the lopinavir/ritonavir (LPV/r) tablet formulation in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in antiretroviral-experienced human immunodeficiency virus type 1 infected subjects with detectable viral load while receiving their current antiretroviral therapy.

NCT00358917
Conditions
  1. Human Immunodeficiency Virus Infections
Interventions
  1. Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
  2. Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
MeSH:Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes
HPO:Immunodeficiency

Virologic Response (HIV-1 RNA <50 Copies/mL) at Week 48 for Participants With 0-2 Protease Inhibitor Substitutions at Baseline Associated With Reduced Response to Lopinavir/Ritonavir. Substitutions considered in the analysis were L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V as defined in the proposed United States Package Insert.. Percentage of Participants With New Primary Protease Mutations at Week 48. --- L10F --- --- K20M --- --- L24I --- --- L33F --- --- M36I --- --- I47V --- --- G48V --- --- I54L --- --- V82A ---

Primary Outcomes

Description: A participant was classified as a responder at the first of 2 consecutive human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) levels <50 copies/mL. The participant continued to be a responder until 2 consecutive values >=50 copies/mL were reached, until the final value if that value was >=50 copies/mL, or until discontinuation or death.

Measure: Percentage of Participants Responding at Week 48 Based on the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) Algorithm

Time: Week 48 (End of Study)

Secondary Outcomes

Measure: Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/Milliliter (mL) at Week 48

Time: Week 48 (End of Study)

Measure: Mean Change From Baseline to Week 48 in Cluster of Differentiation 4 Single-Positive Thymocyte (CD4+ T) Cell Counts

Time: Week 48 (End of Study)

Description: Substitutions considered in the analysis were L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V as defined in the proposed United States Package Insert.

Measure: Virologic Response (HIV-1 RNA <50 Copies/mL) at Week 48 for Participants With 0-2 Protease Inhibitor Substitutions at Baseline Associated With Reduced Response to Lopinavir/Ritonavir

Time: Week 48 (End of Study)

Description: Emergence of new primary protease inhibitor mutations (i.e., mutations at codons 30, 32, 48, 50, 82, 84, and 90 that were not present at baseline).

Measure: Percentage of Participants With New Primary Protease Mutations at Week 48

Time: Week 48 (End of Study)

10 Open-Label, Single-Centre, Randomised Pilot Study to Evaluate Immunovirological and Clinical Evolution of a Combination With Nucleoside Analogues/Nucleotides (Trizivir +Tenofovir) in Multiresistant Patients With Virological Failure

To evaluate whether the combined therapy of two nucleosides plus one nucleotide (Trizivir + TDF) manages to keep CD4 lymphocytes stable in patients with HIV infection on antiretroviral treatment that present virological failure and multiple resistance to antiretrovirals.

NCT00356616
Conditions
  1. HIV Infections
Interventions
  1. Drug: Trizivir (AZT+3HT+Abacavir) twice daily
  2. Drug: Viread (300 mg Tenofovir disoproxil fumarate) once daily
MeSH:HIV Infections

- 5 or more mutations that confer resistance to PI of the following: I10F/I/R/V, V32I, M46I/L, I54V/M/L, V82A/F/T/S/V, I84V/A/C, L90M. --- I10F --- --- V32I --- --- M46I --- --- I54V --- --- V82A ---

Primary Outcomes

Measure: Variations in the immune status of patients in each group throughout follow-up.

Time: 48 weeks

Secondary Outcomes

Measure: Percentage of patients that increase viral load by > 0.5 log

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that increase viral load by > 100,000 copies/mL

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that present some clinical event, B or C classification according to the CDC.

Time: during the 48 weeks of follow-up

Measure: Percentage of patients that present clinical or analytical adverse effects degree > 2 according to the WHO classification.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that drop out of treatment.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that drop out of the study due to intolerance or adverse effects.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of change in lipid determinations.

Time: weeks 12, 24, 36 and 48 with regard to baseline

Measure: Percentage of patients that report changes, improvement or worsening in redistribution of body fat.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that present adherence to the antiretroviral treatment > 95%.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that present improvement in the quality of life (MOS-HIV) and satisfaction questionnaires.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that present an increase in the number of active drugs.

Time: at the end of the study

11 Open-label, Comparative and Randomised Pilot Study to Evaluate the Efficacy and Safety of Saquinavir/Ritonavir in Single Therapy vs Standard HAART Therapy as Maintenance Therapy.

Study the efficacy of Saquinavir/Ritonavir when given in single therapy as maintenance therapy, compared to standard HAART therapies.

NCT00379405
Conditions
  1. HIV Infections
Interventions
  1. Drug: Saquinavir/Ritonavir : 2 capsules (500 mg) / 12 hours
MeSH:HIV Infections

- Documented existence of any of the primary mutations in the protease gene or 3 or more of the following: L10F/I/R/V, K20M/R, M36I/V, I54L/T/V, L63P, A71T/V , V82A/F/T/S, I84A/V OR L90M. --- L10F --- --- K20M --- --- M36I --- --- I54L --- --- L63P --- --- A71T --- --- V82A ---

Primary Outcomes

Measure: Virological response: Viral Load

Time: weeks 24 and 48

Secondary Outcomes

Measure: CD4 and CD8 lymphocyte count.

Time: weeks 24 and 48

Measure: Physical Exploration: including weight, height, index waist/hip (the abdominal perimeter is measured between the last floating rib and the iliac crest), assessment of changes in body fat distribution,...

Time: weeks 24 and 48

Measure: Karnofsky Index.

Time: weeks 24 and 48

Measure: Adverse events.

Time: during the 48 weeks of follow-up

Measure: Trough plasma concentrations of Saquinavir.

Time: during the 48 weeks of follow-up

Measure: Lipid study in plasma (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides)

Time: during the 48 weeks of follow-up

Measure: Serology for Hepatitis B and C virus.

Time: at baseline visit

Measure: Assessment of treatment adherence.

Time: at baseline and weeks 4, 12, 24, 36 and 48

Measure: Assessment of quality of life (by means of the MOS-HIV questionnaire).

Time: at baseline and weeks 4, 12, 24, 36 and 48

Measure: Genotype if virological failure.

Time: at any time of study if it is necessary

12 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 --- --- D67N --- --- K70R --- --- L210W --- --- K219Q --- --- I47V --- --- G48V --- --- I50V --- --- V82A ---

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

13 An Open-Label Phase 3B Study in HIV-Infected Individuals With Viremia on or After Their First-Line Non-Nucleoside Reverse Transcriptase Inhibitor or Integrase Inhibitor-Based Regimen and Starting a Second-Line Regimen Consisting of ATV/RTV or DRV/RTV With an Optimized NRTI Backbone

The purpose of this study is to determine the proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 in patients who failed their first line therapy containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) or an integrase inhibitor

NCT01605084
Conditions
  1. HIV
Interventions
  1. Drug: Atazanavir
  2. Drug: Darunavir
  3. Drug: Ritonavir
  4. Drug: Optimized NRTI backbone

An NRTI or PI (reported with or without ritonavir) with a "partially sensitive" net assessment will not be considered "fully sensitive" 4. Mentally able to participate in the study 5. Men and women ≥ 18 years old - Women of child bearing potential who engage in vaginal intercourse and who are not clinically sterilized must use highly effective methods of birth control during the study Exclusion Criteria: 1. Screening HIV genotype showing presence at baseline of any of the following Protease inhibitor (PI) Mutation Patterns associated with genotypic resistance to Atazanavir sulfate/ Ritonavir or Darunavir/Ritonavir will lead to exclusion: 1. Subjects with any darunavir associated mutations* at baseline (*V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V) 2. Subjects with a major mutation to Atazanavir sulfate consisting of N88S 3. Subjects with more than 3 of any of the following Atazanavir sulfate related mutations:D30N, M36I/V, M46I/L/T, I54V/L/T/M/A, A71V/T/I/G, G73S/A/C/T, V77I, V82A/F/T/S/I, I84V/A, N88D or L90M 2. Subjects with < 1 fully active NRTI on PhenoSense report, other than lamivudine and emtricitabine 3. Diagnosed with active tuberculosis 4. Chronic hepatitis B infection 5. Hepatitis C-positive patients who are not clinically stable or need treatment during the study period 6. --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- I54M --- --- T74P --- --- L76V --- --- I84V --- --- L89V --- --- N88S --- --- M36I --- --- M46I --- --- I54V --- --- A71V --- --- G73S --- --- V77I --- --- V82A ---

Primary Outcomes

Measure: Proportion of subjects with Human immunodeficiency virus 1 (HIV-1) Ribonucleic Acid (RNA) < 50 c/mL

Time: At Week 48

Secondary Outcomes

Measure: Proportion of subjects with HIV-1 RNA < 50 c/mL

Time: At week 24

Measure: Change from baseline in CD4 cell count

Time: Baseline (Week 0) and at week 48

Measure: Incidence rates of serious adverse event (SAEs) and adverse events (AEs) leading to discontinuation

Time: up to week 48

Measure: Incidence rates of antiretroviral resistance measured by newly emergent genotypic substitutions and phenotypic resistance to study drugs for virologic failure

Time: up to week 48

Measure: Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 by baseline M184V presence or absence

Time: Week 48

14 A Randomized, Open-label Study of Lopinavir/Ritonavir 400/100 mg Tablet Twice Daily + Co-formulated Emtricitabine/Tenofovir Disoproxil Fumarate 200/300 mg Once Daily Versus Lopinavir/Ritonavir 400/100 mg Tablet Twice Daily + Raltegravir 400 mg Twice Daily in Antiretroviral Naive, HIV-1 Infected Subjects

The purpose of this study is to compare the safety, tolerability, and antiviral activity of the lopinavir/ritonavir tablet when administered in combination with reverse transcriptase inhibitors to lopinavir/ritonavir tablets when administered in combination with a human immunodeficiency virus type 1 ( HIV-1) integrase inhibitor in antiretroviral naive HIV-1 infected subjects.

NCT00711009
Conditions
  1. Human Immunodeficiency Virus Infection
Interventions
  1. Drug: lopinavir/ritonavir (LPV/r)
  2. Drug: emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
  3. Drug: raltegravir (RAL)
MeSH:Virus Diseases Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes
HPO:Immunodeficiency

Evidence of lopinavir resistance was more conservatively defined as the presence of 1 or more of these mutations: protease I47V or A, G48V, I50V, V82A or F or T or S, I84V, L90M; or presence of at least 3 or more of these mutations: protease L10F or I or R or V, K20M or R, L24I, V32I, L33F, M36I, M46I or L, F53L, any change to I54, A71V or T, and G73S.. Change From Baseline on Physical Component Score of the Medical Outcomes Study HIV Health Survey. --- I47V --- --- G48V --- --- I50V --- --- V82A ---

Primary Outcomes

Description: A participant was classified as a responder at the first of 2 consecutive visits with plasma HIV-1 RNA levels below 40 copies/mL. The participant continued to be a responder until one of the following: the participant had 2 consecutive values greater than or equal to 40 copies/mL; the final measurement, if the final measurement was the first one documenting an increase in plasma HIV-1 RNA level to greater than or equal to 40 copies/mL; the participant discontinued participation in the study or died.

Measure: Percentage of Participants Responding (Plasma HIV-1 Ribonucleic Acid [RNA] Levels Less Than 40 Copies/Milliliter [mL]) at Week 48 Based on the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) Algorithm

Time: Baseline to Week 48

Description: Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Treatment-emergent, moderate or severe drug-related adverse events that occurred in at least 2% of participants in either treatment arm are presented.

Measure: Percentage of Participants With Moderate or Severe Treatment-emergent, Drug-related Adverse Events

Time: Week 96

Description: Potentially clinically significant laboratory values that occurred in at least 2% of participants in either treatment arm are presented.

Measure: Primary Outcome: Percentage of Participants With Potentially Clinically Significant Laboratory Values

Time: Baseline to Week 96

Secondary Outcomes

Description: A participant was classified as a responder at the first of 2 consecutive visits with plasma HIV-1 RNA levels below 40 copies/mL. The participant continued to be a responder until one of the following: 1) the participant had 2 consecutive values greater than or equal to 40 copies/mL; the final measurement, if the final measurement was the first one documenting an increase in plasma HIV-1 RNA level to greater than or equal to 40 copies/mL; the participant discontinued participation in the study or died.

Measure: Percentage of Participants Responding (Plasma HIV-1 RNA Levels Below 40 Copies/Milliliter [mL]) at Each Visit Based on the FDA Time to Loss of Virologic Response (TLOVR) Algorithm

Time: Baseline to Week 96

Measure: Mean Change in CD4+ T-Cell Counts From Baseline to Each Visit

Time: Baseline to Week 96

Description: Time of loss of virologic response was defined as the first of the following: first of 2 consecutive visits with plasma HIV-1 RNA greater than or equal to 40 copies/milliliter (mL), if the participant previously demonstrated 2 consecutive plasma HIV-1 RNA levels below 40 copies/mL; Study Day 1, if the subject never achieved 2 consecutive plasma HIV-1 RNA levels below 40 copies/mL; the day of the final measurement, if the final measurement was the first one documenting an increase in plasma HIV-1 RNA level to greater than or equal to 40 copies/mL.

Measure: Time to Loss of Virologic Response - Percentage of Participants Still Categorized as Responders at Day 672

Time: Baseline to Week 96

Description: Resistance to study drugs was defined as described by the International AIDS Society-USA (IAS-USA) Panel. All participants had an HIV-1 drug resistance genotype (lopinavir/ritonavir, tenofovir, or emtricitabine) obtained at the Screening Visit. Beginning at Week 8, if participant's plasma HIV-1 RNA was greater than or equal to 40 copies/milliliter (mL) and was below 40 copies/mL at the previous visit, additional procedures were undertaken to determine if resistance to study drug occurred.

Measure: Number of Participants Who Developed Resistance to Each Drug in the Study Regimen, as Defined by the International AIDS Society-USA (IAS-USA) Panel.

Time: Baseline to Week 96

Description: Beginning at Week 8, if participant's plasma HIV-1 RNA was greater than/equal to 40 copies/milliliter (mL) and was below 40 copies/mL at the previous visit, additional procedures were undertaken to determine if resistance occurred. Evidence of lopinavir resistance was more conservatively defined as the presence of 1 or more of these mutations: protease I47V or A, G48V, I50V, V82A or F or T or S, I84V, L90M; or presence of at least 3 or more of these mutations: protease L10F or I or R or V, K20M or R, L24I, V32I, L33F, M36I, M46I or L, F53L, any change to I54, A71V or T, and G73S.

Measure: Number of Participants Who Developed Resistance, Defined Conservatively, to Lopinavir

Time: Baseline to Week 96

Description: The Survey is a brief, comprehensive health status measure used in studies of people with HIV/AIDS. Participants rate their health and mental/emotional condition, how much their health limits physical activities (eating, dressing, bathing, climbing stairs, walking one block, etc.) and social activities (for example, visiting with friends or relatives), and other questions that measure quality of life. The physical component summarizes answers to questions about physical status. Possible scores range from 0 to 100. A higher score indicates better health, and increases indicate improvement.

Measure: Change From Baseline on Physical Component Score of the Medical Outcomes Study HIV Health Survey

Time: Baseline to Week 96

Description: The Survey is a brief, comprehensive health status measure used in studies of people with HIV/AIDS. Participants rate their health and mental/emotional condition, how much their health limits physical activities (eating, dressing, bathing, climbing stairs, walking one block, etc.) and social activities (visiting with friends or relatives, etc.), and other questions that measure quality of life. The mental component summarizes answers to questions about emotional and mental wellbeing. Possible scores range from 0 to 100. Higher scores indicates better health, and increases indicate improvement.

Measure: Change From Baseline on Mental Component of Medical Outcomes Study HIV Health Survey

Time: Baseline to Week 96

Description: The Effectiveness Scale of the TSQM evaluates the participant's satisfaction or dissatisfaction (1=extremely dissatisfied to 7=extremely satisfied) with the ability of the medication to prevent or treat the condition, the way the medication relieves symptoms, the amount of time it takes for the medication to start working, and other questions. Scores are converted to a range of 0 to 100. A higher score indicates greater satisfaction.

Measure: Score on Effectiveness Scale of Treatment Satisfaction Questionnaire for Medication (TSQM)

Time: Week 96

Description: The Side Effects scale of the TSQM asks if the participant experiences side effects (yes/no), and if so, how bothersome the side effects are, to what extent they interfere with physical health and ability to function (for example, strength and energy levels), to what extent they interfere with mental function (for example, ability to think clearly, stay awake, etc.), and to what extent the side effects affect the participants overall satisfaction with the medication. Scores are converted to a range of 0 to 100. Higher scores indicate less interference and/or less dissatisfaction.

Measure: Score on Side Effects Scale of Treatment Satisfaction Questionnaire for Medication

Time: Week 96

Description: The Global Satisfaction scale of the TSQM evaluates the participants rating of whether the good things about the medication outweigh the bad things (1=not at all certain to 5=extremely certain) and how satisfied or dissatisfied the participant is with the medication (1=extremely dissatisfied to 7=extremely satisfied). Scores are converted to a range of 0 to 100. Higher scores indicate greater satisfaction.

Measure: Score on Global Satisfaction Scale of Treatment Satisfaction Questionnaire for Medication

Time: Week 96

Measure: Mean Change From Baseline in Hemoglobin (Grams/Liter)

Time: Baseline to Week 96

Description: Hematocrit fraction is the percentage (%) by volume of packed red blood cells (RBCs) in the participant's blood. It was measured using standard clinical laboratory analysis of participants' blood samples.

Measure: Mean Change From Baseline in Hematocrit (Fraction)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Red Blood Cell Count (x 10^12/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Platelet Count (x 10^9/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in White Blood Cell Count (x 10^9/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Neutrophils (x 10^9/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Lymphocytes (x 10^9/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Monocytes (x 10^9/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Eosinophils (x 10^9/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Basophils (x 10^9/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Alanine Aminotransferase (Units/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Aspartate Aminotransferase (Units/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Alkaline Phosphatase (Units/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Creatine Phosphokinase (Units/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Total Bilirubin (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Creatinine (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Blood Urea Nitrogen (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Uric Acid (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Inorganic Phosphate (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Calcium (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Sodium (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Potassium (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Chloride (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Bicarbonate (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Albumin (Grams/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Total Protein (Grams/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Cholesterol (Micromoles/Liter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in High Density Lipoprotein Cholesterol (HDL) (Micromoles/Liter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Low Density Lipoprotein (LDL) (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Low Density Lipoprotein (LDL): High Density Lipoprotein (HDL) Ratio (Ratio)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Triglycerides (Micromoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Calculated Creatinine Clearance (Milliliters/Second)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Fasting Glucose (Millimoles/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Lactate Dehydrogenase (Units/Liter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Lipase (Units/Liter)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Magnesium (Millimoles/Liter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Adiponectin (Micrograms/Milliliter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Interleukin-6 (Nanograms/Liter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Lactate (Millimoles/Liter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-1 (Picograms/Milliliter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-2 (Picograms/Milliliter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Leptin (Nanograms/Milliliter)

Time: Baseline to Week 96

Description: Included in measures of metabolic toxicity

Measure: Mean Change From Baseline in Insulin (Picomoles/Liter)

Time: Baseline to Week 96

Description: Urine specific gravity is a laboratory test that measures the concentration of all chemical particles in the urine. The measurement produces a ratio of the urine density to water density.

Measure: Mean Change From Baseline in Urine Specific Gravity

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Urine pH

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Sitting Systolic Blood Pressure (mm Hg)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Sitting Diastolic Blood Pressure (mm Hg)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Sitting Heart Rate (Beats Per Minute)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Weight (kg)

Time: Baseline to Week 96

Measure: Mean Change From Baseline in Temperature (°F)

Time: Baseline to Week 96

Description: Chest circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Participant's chest circumference was measured at 5 cm above the xiphoid process using non-stretchable measuring tape with half centimeter marks.

Measure: Mean Change From Baseline in Chest Measurement (cm)

Time: Baseline to Week 96

Description: Waist circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Circumference of participant's waist was measured at the level of the navel using non-stretchable measuring tape with half centimeter marks.

Measure: Mean Change From Baseline in Waist Measurement (cm)

Time: Baseline to Week 96

Description: Arm circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Particpant's arm circumference was measured halfway between the acromial process on the shoulder and the tip of the elbow (olecranon process) using non-stretchable measuring tape with half centimeter marks.

Measure: Mean Change From Baseline in Mid-Arm Measurement (cm)

Time: Baseline to Week 96

Description: Hip circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Participant was measured at widest width of the hip using non-stretchable measuring tape with half centimeter marks.

Measure: Mean Change From Baseline in Hips Measurement (cm)

Time: Baseline to Week 96

Description: Mid-thigh circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Particpant's thigh circumference was measured halfway between the inguinal crease and the midpoint of the upper border of the patella using non-stretchable measuring tape with half centimeter marks.

Measure: Mean Change From Baseline in Mid-Thigh Measurement (cm)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Fat (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Lean Mass (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Total Mass (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Fat (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in DEXA Scan of Lower Extremity Lean Mass (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Total Mass (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Fat (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Lean Mass (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Mass (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Fat (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Lean Mass (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Mass (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan of bone mineral content was used to evaluate potential bone effects of treatment.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Content (Grams)

Time: Baseline to Week 96

Description: The dual energy X-ray absorptiometry (DEXA) scan of bone mineral content was used to evaluate potential bone effects of treatment.

Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Density (Grams/cm^2)

Time: Baseline to Week 96

15 A Phase II Randomized, Controlled, Partially Blinded Trial to Investigate Dose-response of TMC114/RTV in 3-class-experienced HIV-1 Infected Subjects, Followed by an Open-label Period on the Recommended Dose of TMC114/RTV.

The purpose of this study is to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir

NCT00650832
Conditions
  1. HIV
Interventions
  1. Drug: TMC114; darunavir; Prezista

Inclusion Criteria: - Patients with documented HIV-1 infection - Patients receiving a PI-containing regimen at screening initiated at least 8 weeks prior to screening with plasma HIV-1 RNA > 1000 copies/mL - Prior use of more than 1 NRTI for at least 3 months in total - Prior use of one or more NNRTIs (investigational included) as part of a failing regimen - Patients having at least 1 primary PI mutation at screening as defined by the IAS guidelines (D30N, M46I/L, G48V, I50V/L, V82A/F/T/S, I84V, L90M)16 - patients experienced to at least one PI for a total period of at least 3 months - Patients voluntarily signs the informed consent form - Patients can comply with the protocol requirements - Patients having a general medical condition that, in the investigator's opinion, does not interfere with the assessments and the completion of the trial. --- D30N --- --- M46I --- --- G48V --- --- I50V --- --- V82A ---

Primary Outcomes

Measure: The primary objective of the trial is to compare all TMC114/RTV dose groups with control at Week 24 (the primary endpoint) by means of the confirmed virologic response, defined as a drop in viral load of at least 1 log10 versus baseline.

Secondary Outcomes

Measure: To evaluate safety and tolerability over 24 to 144 weeks; To evaluate the durability of the antiviral activity; To investigate the dose-response by comparing the different TMC114/RTV dosages.

16 Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r) in Adolescents With CD4 + T Cells > 350 Cells/mm3 Initiating HAART

This study proposes to evaluate a pre-DHHS guideline of HAART initiation and then de-intensification management strategy in adolescents with mild immunosuppression and compare changes in CD4% from baseline to week 48 and then during de-intensification.

NCT00491556
Conditions
  1. HIV Infections
Interventions
  1. Procedure: Early Initiation of Highly Active Anti-Retroviral Therapy
  2. Procedure: Standard Care
MeSH:HIV Infections

The following genotypic mutations exclude subjects from participation in ATN 061: Major ATV mutations I50L; I84V; N88D/S, Major PI mutations including: D30N; V32I; L33I/F/V; M46I/L; I47V/A; G48V; I50V/L; I54V/L/A/M/T/S; L76V; V82A/F/T/S/L; L90M, Any major PI mutation as defined by the most current IAS-USA Drug Resistance Mutations Figures that would adversely affect a subject's future PI choices, Major RT mutations: Q151M and 69 insertion complex; Decisions regarding the selection of an NRTI backbone for subjects with NRTI resistance mutations other than those described above will be made by the site PI in consultation with the protocol chair or his designee. --- I50L --- --- I84V --- --- N88D --- --- D30N --- --- V32I --- --- L33I --- --- M46I --- --- I47V --- --- G48V --- --- I50V --- --- I54V --- --- L76V --- --- V82A ---

Primary Outcomes

Measure: Difference in CD4+ T Cell Percentage Between Week 0 and Week 48

Time: Week 0 and Week 48

Measure: Difference in CD4+ T Cell Percentage Between Week 48 and Week 152

Time: 152 Weeks

Secondary Outcomes

Measure: Difference in CD4+ T Cell Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ T Cell Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD4+ Naïve T Cell Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ Naïve T Cell Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD4+ Termed Central Memory (TCM) Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ TCM Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD4+ Effector Memory (TEM)Ro Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ TEMRo Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD4+ TEMRa Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ TEMRa Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8+ Naïve T-Cell Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8+ Naïve T-Cell Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8+ TCM Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8+ TCM Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8+ TEMRo Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8+ TEMRo Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8+ TEMRa Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8+ TEMRa Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 Naïve CD28 Cell Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 Naïve CD28 Cell Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 Naïve CD38 Cell Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 Naïve CD38 Cell Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 Naïve CD57 Cell Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 Naïve CD57 Cell Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 Naïve T-Cell Percentage Expressing Human Leukocyte Antigen-D Related (HLA-DR) Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 Naïve T-Cell Percentage Expressing HLA-DR Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TCM CD28 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TCM CD28 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TCM CD38 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TCM CD38 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TCM CD57 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TCM CD57 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TCM HLA-DR Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TCM HLA-DR Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRo CD28 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRo CD28 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRo CD38 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRo CD38 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRo CD57 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRo CD57 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRO HLADR Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRo HLA-DR Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRa CD28 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRa CD28 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRa CD38 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRa CD38 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRa CD57 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRa CD57 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRa HLA-DR Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRa HLA-DR Percentage Between Week 48 and Week 152

Time: 152 weeks


HPO Nodes


HP:0002721: Immunodeficiency
Genes 269
CHD7 ACP5 JAK3 TNFRSF4 NFE2L2 NFKB2 SRP54 MS4A1 LCK STAT1 EPG5 PRPS1 CUL4B CD19 MEIS2 CCDC47 GATA1 CD3E CTPS1 POLE ARVCF CDH23 ATM IRAK4 PRKDC RREB1 RAG2 RAG2 SLC46A1 PGM3 FOXN1 IL2RG LMNB2 CTBP1 JMJD1C PIK3CD CREBBP HYOU1 FCGR3A TBX1 PNP SPATA5 UNG TNFSF12 TERT PTEN MALT1 TBX1 CD81 UNC119 WIPF1 TNFRSF1B PARN NSD2 TTC7A HIRA SPATA5 GP1BB GATA2 ZBTB24 IRF7 CD19 CD81 UNC93B1 EP300 TNFRSF13B SEC24C IL2RB TRAF3 CRKL DCLRE1C CDC42 IL7R DCTN4 CLCA4 ATRX SIK3 IGLL1 SEC23B CHD1 AK2 XRCC4 TCF3 IGHM CD79A PIK3R1 NOP10 MS4A1 CD79B BCL11B BUB1B AGL IVNS1ABP TTC37 PTPRC FOXN1 TNFRSF13C KNSTRN TYK2 TINF2 BCL10 RAG1 RNF168 RTEL1 CYBA IL7R USB1 CD3G PKP1 RAC2 USF3 CR2 CARD11 LAMTOR2 CYBB POLE ICOS DNAJC21 SH2D1A DNMT3B IL21 ADA CPLX1 IL2RA PIK3CA PGM3 LYST CD3D CDCA7 PIK3R1 ICOS FRAS1 LIG4 CARD9 SDHC DCLRE1C DNMT3B NCF1 RAG1 ORAI1 ACD SKIV2L IL2RG ZBTB24 TINF2 MAGT1 CD40 IKBKG TNFRSF13B WAS CR2 TFRC NFKB1 FGFRL1 USP8 CD247 RMRP WRAP53 UFD1 IKBKG AP3D1 DKC1 IL12RB1 IL12B RTEL1 SHANK3 ISG15 STAT1 MBTPS2 IRF8 RMRP TNFRSF13C NFKB1 SMARCAL1 IRF8 TERT MYC RAG1 BTK RNF168 SP110 NFKB2 PIK3CD IKBKB RBCK1 LAT ADA HELLS XRCC4 DOCK2 CDC42 TICAM1 MTHFD1 SKIV2L RAG2 STAT1 ANTXR2 IRAK4 CD40LG IFNGR1 AICDA DKC1 SDHB IKZF1 RAB27A CD28 CREBBP MYD88 TLR3 CTC1 ADA2 NCF2 STIM1 LYST IRF2BP2 AKT1 CTLA4 LETM1 STX1A TNFRSF13C TBK1 CORO1A CFTR SBDS WHCR ICOS EFL1 TERC XIAP TTC7A RAG1 UROS LIG4 PARN AK2 BCR DKC1 SDHD LRRC8A KLLN HBB LRBA TGFB1 MAN2B1 NHP2 NHEJ1 NPM1 EXTL3 EPG5 MAN2B1 COMT PRKCD BLNK CR2 TBCE IL2RG CTLA4 RTEL1 MMUT LAMTOR2 TNFSF12 IFNGR2 MAPK1 IL21R ACTB CHD1 CD19 STK4 XIAP
SNP 0