SNPMiner Trials by Shray Alag


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Report for Mutation L100I

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 7 clinical trials

Clinical Trials


1 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 HIV-1 Drug: Maraviroc + Zidovudine/Lamivudine Drug: Efavirenz + Zidovudine/Lamivudine Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine

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).. 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. --- K103N --- --- Y181C --- --- Y188C --- --- G190A --- --- V106A --- --- L100I ---

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

2 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 HIV Infections Drug: raltegravir potassium Drug: darunavir/ritonavir Drug: etravirine 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 --- --- I84V --- --- N88S --- --- L90M --- --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- G73S --- --- L76V --- --- I84V --- --- L89V --- --- A98G --- --- L100I ---

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

3 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 HIV Infections Drug: matching placebo 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 ---

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

4 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 HIV Infections Drug: Etravirine (Intelence) Drug: Truvada
MeSH: Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome

Any of the following nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations: V90I, A98G, L100I, K101E/H/P/Q, K103H/S/T, V106A/I/M, V108I, E138A/G/K/Q, V179D/E/F/G/I/T, Y181C/I/V, Y188C/H/L, V189I, G190A/C/E/Q/S, H221Y, P225H, F227C/L, M230I/L, P236L, K238N/T, K103N. --- V90I --- --- A98G --- --- L100I ---

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

5 A Multicenter, Single Arm, Open-Label Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients

This study is a Phase II single arm, open-label, multicenter, study of 50 human immunodeficiency virus-1 (HIV) infected adult patients, all of whom will receive etravirine (ETR) 400mg and DRV/r 800/100mg each given orally once daily. This trial is designed to evaluate the efficacy of the aforementioned ARV regimen, as measured by the percentage of patients with HIV RNA <50 copies/mL at 48 weeks, in early treatment-experienced HIV-infected patients. In addition to general safety parameter measurements, this trial will also assess changes in metabolic, inflammatory, immune restoration, and bone markers. Screening will occur over a 6-week period. The primary endpoint will be assessed at Week 48, and the treatment period is 48 weeks. The end of study endpoint will be met by either completing the Week 48 visit, or by early termination from the study for any reason.

NCT01199939 Human Immunodeficiency Virus (HIV) Drug: Etravirine Drug: Ritonavir Drug: Darunavir
MeSH: Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes
HPO: Immunodeficiency

Inclusion Criteria: - Male or female patients, aged 18 years or above - Patients with documented HIV-1 infection - On current HAART regimen for at least 12 weeks continuous duration at screening, and with an HIV-1 plasma viral load above 500 HIV-1 RNA copies/mL by site's currently utilized viral load assay (Note: For the purposes of this study, HAART is defined as treatment with a combination of 3 or more HIV antiretroviral medications from at least 2 different classes of medications (NRTIs, NNRTIs, PIs, integrase inhibitors, CCR5 antagonists, fusion inhibitors)) - No more than 2 previous virologic failures while on PI-containing HAART regimens where virologic failure is generally defined as either a lack of suppression of the subjects' viral load to lower limit of quantification (per standard assay historically used in care) after 24 weeks of treatment or, rebound of a previously suppressed viral load (undetectable per investigator's standard of care) to detectable limits and without demonstrated re-suppression on the same regimen - Demonstrated phenotypic sensitivity to both etravirine and darunavir based on resistance testing at Screening (FC= 2.9 for etravirine and FC = 10.0 for darunavir using the PhenoSense GT) - The absence of all of the following Resistance Associated Mutations (RAMS) at baseline: For Darunavir: V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V - For Etravirine: L100I, E138A, I167V, V179D, V179F, Y181I, Y181V, G190S - 7. CD4 count = 50 cells/mm3. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P --- --- L76V --- --- I84V --- --- L89V --- --- L100I ---

Primary Outcomes

Description: CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.

Measure: Number of Participants With Confirmed Virologic Response (CVR) at Week 48

Time: Week 48

Secondary Outcomes

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 4

Time: Baseline (Day 1) and Week 4

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 8

Time: Baseline (Day 1) and Week 8

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 12

Time: Baseline (Day 1) and Week 12

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 16

Time: Baseline (Day 1) and Week 16

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 20

Time: Baseline (Day 1) and Week 20

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 24

Time: Baseline (Day 1) and Week 24

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 30

Time: Baseline (Day 1) and Week 30

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 36

Time: Baseline (Day 1) and Week 36

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 42

Time: Baseline (Day 1) and Week 42

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 48

Time: Baseline (Day 1) and Week 48

Description: CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.

Measure: Time to Reach First Confirmed Virologic Response

Time: Baseline (Day 1) to Week 48

Description: Virologic Failure is defined as participant who is a rebounder or a non-responder. Rebounder participant is defined as a participant who is still in the study at Week 12 and first achieves 2 consecutive virologic responses (<50 copies/mL) followed by 2 consecutive non-responses or a discontinued participant (any reason) for which the last observed time point shows a non-response. Non responder participant is defined as a participant who is still in the study at Week 12 and never achieves 2 consecutive responses.

Measure: Number of Participants With Virologic Failure

Time: Baseline (Day 1) to Week 48

Measure: Change From Baseline in Cluster of Differentiation 4 (CD4+) and Cluster of Differentiation 8 (CD8+) Cell Counts at Week 48

Time: Baseline (Day 1) and Week 48

6 Dolutegravir + Rilpivirine Switch Study (DORISS): Pilot and Noninferiority Trial Comparing Dolutegravir + Rilpivirine vs. Continued HAART (Highly Active Antiretroviral Therapy) in Patients With Plasma HIV RNA ≤ 50 Copies/mL for at Least 2 Years

The primary objective of the study is to evaluate the capacity of Dolutegravir + Rilpivirine vs. continued triple combination HAART to maintain plasma HIV RNA ≤ 50 copies/ml throughout 24 weeks in patients with plasma HIV RNA ≤ 50 copies/mL for at least 2 years under conventional HAART (2 NNRTI + 3rd agent). The main secondary objectives are the following: - % of virologic success (plasma viral load ≤ 50 copies/mL) at W24 and W48 - % of patients who maintain a plasma viral load ≤ 50 copies / ml from D0 to W48 - % of virological failure defined by two consecutive plasma viral load > 50 copies/mL - Profile of genotypic resistance in case of virological failure. The trial will be conducted according to the design below, in 3 steps: - Step 1: enrollment of 80 patients (40 in each arm) - Step 2: enrollment on hold until W16 data from the 40 patients enrolled in the intervention arm have been analyzed. - Step 3: resumption and completion of enrollment if conditions for resuming enrollment at the end of step 2 are fulfilled, i.e. if the percentage of patients randomized to the intervention arm who have a plasma viral load ≤ 50 copies/mL from D0 to W16 is significantly > 70%, which translates in a maximum of 6 virologic failures.

NCT02069834 HIV Infection HAART-treated Virologically Controlled Drug: Arm 1 (intervention) Drug: Arm 2 (control)
MeSH: HIV Infections

- Plasma HIV-RNA ≤ 50 copies/mL for > 2 years - CD4 cell count > 350/mm3 for > 6 months - No prior virologic failure under an NNRTI-containing or an INSTI-containing ART regimen - No NNRTI mutation on pre-ART genotype (if no pre-ART genotype available: no NNRTI mutation on DNA genotype at screening) among the following: K101E/P, E138A/G/K/Q/R/S, V179L, Y181C/I/V, Y188L, H221Y, M230I/L/V, L100I + K103N/S, L100I +K103R +V179D. --- K101E --- --- E138A --- --- V179L --- --- Y181C --- --- Y188L --- --- H221Y --- --- M230I --- --- L100I ---

- Plasma HIV-RNA ≤ 50 copies/mL for > 2 years - CD4 cell count > 350/mm3 for > 6 months - No prior virologic failure under an NNRTI-containing or an INSTI-containing ART regimen - No NNRTI mutation on pre-ART genotype (if no pre-ART genotype available: no NNRTI mutation on DNA genotype at screening) among the following: K101E/P, E138A/G/K/Q/R/S, V179L, Y181C/I/V, Y188L, H221Y, M230I/L/V, L100I + K103N/S, L100I +K103R +V179D. --- K101E --- --- E138A --- --- V179L --- --- Y181C --- --- Y188L --- --- H221Y --- --- M230I --- --- L100I --- --- K103N --- --- L100I ---

Primary Outcomes

Measure: Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16)

Time: Week 16

Measure: Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks

Time: Week 24

Secondary Outcomes

Measure: Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48

Time: Week 48

Measure: Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48

Time: Week 48

Measure: Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL

Time: Week 48

Measure: Measure of the profile of genotypic resistance in plasma in case of virologic failure

Time: Week 48

Measure: Percentage of patients who discontinued or changed the strategy of the study

Time: Week 48

Description: Evolution of the HIV-DNA between Day 0 and week 48

Measure: Measure of the HIV-DNA between day 0 and week 48

Time: W48

Description: Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0

Measure: Measure of CD4 lymphocytes at week 24 compared to day 0

Time: Week 24

Description: Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0

Measure: Measure of CD4 lymphocytes at Week 48 compared to Day 0

Time: Week 48

Description: Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events

Measure: Number of patients with adverse events of grade 2 to 4

Time: Week 48

Description: Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0

Measure: Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0

Time: Week 24

Description: Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0

Measure: Measure of changes in serum lipid parameters at week 48 to Day 0

Time: Week 48

Description: Changes in fat mass distribution at Week 24 compared to Day 0

Measure: Measure of changes in fat mass distribution at week 24 compared to Day 0

Time: Week 24

Description: Changes in fat mass distribution at Week 48 compared to Day 0

Measure: Measure of changes in fat mass distribution at Week 48 compared to Day 0

Time: Week 48

Description: Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire

Measure: Measure of adherence to treatment at Week 24 compared to Day 0

Time: Week 24

Description: Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire

Measure: Measure of adherence to treatment at Week 48 compared to Day 0

Time: Week 48

Description: Assessment of patient satisfaction for their treatment at D0 by questionnaire

Measure: Measure of patient satisfaction for their treatment at Day 0

Time: Day 0

Description: Assessment of patient satisfaction for their treatment at Week 24 by questionnaire

Measure: Measure of patient satisfaction for their treatment at Week 24

Time: Week 24

Description: Assessment of patient satisfaction for their treatment at Week 48 by questionnaire

Measure: Measure of patient satisfaction for their treatment at Week 48

Time: Week 48

Description: Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .

Measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .

Time: Week 24

Description: Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .

Measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .

Time: Week 48

Description: Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4

Measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4

Time: Week 4

Description: Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24

Measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24

Time: Week 24

Measure: Measure of the profile of genotypic resistance in plasma in case of virologic failure

Time: Week 24

Measure: Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL

Time: Week 24

7 A Phase IV 48 Week, Open Label, Pilot Study of Darunavir Boosted by Cobicistat in Combination With Rilpivirine to Treat HIV+ Naïve Subjects (PREZENT)

Current HIV treatment guidelines recommend the use of triple-drug therapy (two nucleoside reverse transcriptase inhibitors and either a protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or an integrase inhibitor) for the treatment of antiretroviral (ARV)-naïve patients. With the introduction of highly active antiretroviral therapy (HAART), patients with HIV are living much longer. With the increasing lifespan of persons with HIV, long-term complications from therapy as well as the occurrence of co-morbidities with aging have prompted HCPs to re-think the current treatment paradigm and consider novel combinations of ARVs. All of the currently approved HIV antiretrovirals have been implicated in causing long-term toxicities; however the greatest body of evidence for long-term metabolic effects has implicated the nucleoside reverse transcriptase (NRTI) class. By utilizing a non-NRTI treatment regimen, it is hypothesized that many of these long-term metabolic effects (renal toxicity, bone loss, body fat changes) can be delayed or avoided altogether. The clinical data on novel combinations is currently limited but rapidly growing and has included several combinations that have utilized darunavir. This study will be the first of its kind using the unique combination of darunavir/cobicistat and rilpivirine. Currently, this drug combination is not a recommended option for first time treatment of HIV

NCT02404233 HIV Positive Drug: darunavir/cobicistat Drug: rilpivirine
MeSH: HIV Seropositivity

Exclusion Criteria 1. Patient with active AIDS-defining opportunistic infection or disease according to the 1993 CDC AIDS surveillance definition (Clinical Category C) in the 30 days prior to baseline and that, in the opinion of the investigator, would preclude the patient from participating in the study (See Appendix C). 2. Patient has none of the following darunavir-associated RAMs: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V 3. Having documented genotypic evidence of NNRTI resistance at screening or from historical data available in the source documents, i.e. at least one of the NNRTI rams from the following list; K101E, K101P, E138A, E138G, E138K, E138R, E138Q, , V179L, Y181C, Y181I, Y181V, Y188L, H221Y, F227C, M230I, M230L, or the combination of the K103N and L100I. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- I54M --- --- T74P --- --- L76V --- --- I84V --- --- L89V --- --- K101E --- --- K101P --- --- E138A --- --- E138G --- --- E138K --- --- E138R --- --- E138Q --- --- V179L --- --- Y181C --- --- Y181I --- --- Y181V --- --- Y188L --- --- H221Y --- --- F227C --- --- M230I --- --- M230L --- --- K103N --- --- L100I ---

Primary Outcomes

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

Time: up to weeks 48

Secondary Outcomes

Measure: Proportion of patients with plasma HIV-1 RNA <400 copies/mL at each time point evaluated

Time: At week 4, week 12, week 24, week 36, week 48

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

Time: At week 4, week 12, week 24


HPO Nodes


Immunodeficiency
Genes 257
LETM1 NFKB2 EPG5 BCL10 AK2 MS4A1 RTEL1 IFNGR2 LIG4 NFKB1 AGPAT2 FCGR3A NFKB2 RNF168 TERT ZBTB24 CHD1 ATRX ANTXR2 PKP1 WIPF1 NOP10 GATA2 HYOU1 XRCC4 SDHD NHP2 IRAK4 CORO1A TBX1 RBCK1 MALT1 TNFRSF4 LAT CD247 IL2RG PARN EPG5 BSCL2 PARN AK2 IRF7 ICOS GATA1 TNFSF12 USB1 ACTB SMARCAL1 UNG TYK2 IL21R TTC7A IL2RB STAT1 IKBKG FGFRL1 FOXN1 HIRA CCDC47 CLCA4 ACD TNFRSF13B MYC AICDA IRAK4 CD3G FCN3 CYBA CTBP1 CHD1 LAMTOR2 LIG4 CAVIN1 SIK3 IL7R LCK ICOS NPM1 MYD88 ORAI1 RAG2 CARD11 PTEN IGHM PTPRC LAMTOR2 RAG1 PGM3 ARVCF TNFRSF1B TNFRSF13C IRF8 SEC24C IL2RG COG6 IKBKG CD28 DKC1 POLE CR2 ADA JMJD1C TCF3 AP3D1 MBTPS2 SHANK3 HELLS COMT UFD1 RAG2 TTC37 IFNGR1 BCL11B CD19 CARD9 BLNK PRKDC CR2 BUB1B MEIS2 RAG1 SDHC NSD2 CTPS1 DOCK2 CDCA7 LMNB2 IRF2BP2 CD79B TERC LYST CD19 FOS CD3E TFRC NCF1 NHEJ1 IRF8 CTC1 LYST LRBA DNMT3B CAV1 CRKL STX1A MAGT1 CPLX1 TNFRSF13B MMUT DCLRE1C RMRP GP1BB CTLA4 DCLRE1C SKIV2L LRRC8A CD81 ICOS TGFB1 XIAP XRCC4 IL7R TTC7A SKIV2L TBCE RTEL1 IGLL1 NCF2 IL21 UNC119 SIN3A WHCR TNFRSF13C ISG15 JAK3 CD79A RAG1 USP8 CD19 CR2 STAT1 CD3D CFTR CYBB IL12RB1 WAS AKT1 IL2RA HBB IKBKB ATM STAT1 STK4 PRKCD ACP5 IKBKG SH2D1A MTHFD1 CDC42 ADA2 PGM3 RAG1 XIAP MAPK1 PIK3R1 SLC46A1 CHD7 MS4A1 FOXN1 RREB1 CDH23 KLLN WRAP53 CD40LG SEC23B ZBTB24 PIK3CA BTK FRAS1 TINF2 RAC2 IKZF1 RAB27A DKC1 DCTN4 TINF2 CD81 DKC1 RAG2 PRPS1 NFKB1 IKBKG IL2RG BCR UROS TNFRSF13C POLE SPATA5 TNFSF12 SDHB ADA CUL4B PIK3R1 STIM1 PIK3CD IL12B SP110 NFE2L2 PPARG TBX1 RNF168 AGL RTEL1 RMRP TERT CD40 DNMT3B