SNPMiner Trials (Home Page)
Report for Mutation L210W
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 12 clinical trials
Clinical Trials
1 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 HIV Infection Hepatitis C Drug: Kaletra (lopinavir/ritonavir) Drug: Sustiva (efavirenz) 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 ---
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 signsMeasure: Physical examinations
Measure: Clinical laboratory tests
2 Cell Cycle Independent Antiretroviral Therapy: Combination of Nevirapine, FTC, and Tenofovir
Open label, two year study of the clinical efficacy of the combination of FTC, Tenofovir, and Nevirapine. Sixty HIV infected patients without previous exposure to antiretroviral therapy will be enrolled. Study will include a pharmacokinetic substudy to evaluate the interaction of FTC and Nevirapine. Truvada may be used.
NCT00344461 HIV Drug: Nevirapine, FTC, and Tenofovir
Evidence of mutation associated with primary drug resistance to Nevirapine (K103N, Y181C, Y188L, G190S), Tenofovir (M41L, T69 insertion, Q151M, L210W,and K65R), and/or FTC (184V) previously documented, or at time of screening. --- K103N --- --- Y181C --- --- Y188L --- --- G190S --- --- M41L --- --- Q151M --- --- L210W ---
Primary Outcomes
Description: The primary outcome is sustained Virologic response, defined as HIV-1 RNA <500 copies/mL until trial completion at 96 weeks.
Measure: Number of Participants With Sustained Virologic Response Time: 96 WeeksSecondary Outcomes
Description: The number of participants with grades 2,3 and 4 adverse events and laboratory toxicities.
Measure: Patients With Grade 2, 3 and 4 Adverse Events and Laboratory Toxicities Time: Protocol length is 96 weeksDescription: The number of participants with plasma HIV RNA < 50 copies/mL
Measure: Patients With Plasma HIV RNA < 50 Copies/mL Time: 96 weeks.Description: The number of participants with plasma HIV RNA < 400 copies/mL
Measure: Patients With Plasma HIV RNA < 400 Copies/mL Time: 96 weeksDescription: Percent Change From Baseline in Plasma HIV RNA at 96 weeks
Measure: Change in Plasma HIV RNA From Baseline to Week 96 Time: Baseline to week 96Description: To determine the mean change from Baseline in CD4 cell count to week 96.
Measure: Changes in CD4 Cell Count From Baseline and Week 96 Time: Baseline to week 963 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 HIV Infections Drug: Trizivir (AZT+3HT+Abacavir) twice daily Drug: Viread (300 mg Tenofovir disoproxil fumarate) once daily MeSH:HIV Infections
5. Genotype or phenotype resistance to three families of antiretrovirals (PI, NTRI and NNRTI) demonstrated in genotype study carried out in the last 48 weeks and defined as: - 3 or more TAMS of the following: M41L, E44D, D67N, V118I, L210W, T215Y/F, K219Q/E. --- M41L --- --- E44D --- --- D67N --- --- V118I --- --- L210W ---
Primary Outcomes
Measure: Variations in the immune status of patients in each group throughout follow-up. Time: 48 weeksSecondary Outcomes
Measure: Percentage of patients that increase viral load by > 0.5 log Time: weeks 12, 24, 36 and 48Measure: 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
4 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 ---
Primary Outcomes
Measure: HIV-1 RNA change from baseline over the first 14 days of study Time: 14 daysSecondary Outcomes
Measure: safety and tolerability; pharmacokinetics Time: 14 days5 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
2. Any of the following NRTI mutations: M184V/I, K70E/R, K65R, M41L, 69 insert, L210W, T215Y/F, K219Q/E, L74V. --- M184V --- --- K70E --- --- K65R --- --- M41L --- --- L210W ---
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 weeksSecondary 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeks6 Open Label, Randomized Trial of TDF/FTC+Raltegravir Vs. TDF/FTC+Efavirenz in HIV-1-Infected Women: Differential Effects on Viral Suppression/Reservoir, & Immune Parameters in Different Compartments, Including Gut & Genital Tract
Raltegravir not only has a unique mechanism of action, but may also have other unique effects on suppression of viral replication, viral reservoir, and immune reconstitution in blood and other important compartments. This may in part be due to the pharmacokinetics of Raltegravir in blood and gut tissue. Efavirenz will be the comparator antiretroviral drug in this study, with both drugs being used as part of a three-drug regimen with tenofovir and emtricitabine. The primary objectives are to determine differences in the effects of 2 anti-retroviral regimens, Raltegravir + Truvada versus Atripla, with respect to: 1. Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization). 2. Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract. 3. Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine profiles. The secondary objective is to determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz.
NCT00984152 HIV-1 Infections Drug: TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily Drug: TDF/FTC + Efavirenz (Atripla) Once-Daily
Exclusion Criteria: 1. Menopausal (may affect quantity of genital tract secretions) or any serious illness that requires treatment and/or hospitalization until the patient completes therapy 2. Any active infection, including co-infection with hepatitis B or C 3. Any neoplasm 4. Immunosuppressive therapy 5. Requirement for any medications that are prohibited by any of the study treatments 6. Significant liver or renal dysfunction 7. Baseline resistance to any of the study drugs by genotypic testing - NRTI: M41L, K65 R, D76N, T69D, K70R, L74V/I, y115F, Q151M, M184V, L210W, T215any, K219Q/E - NNRTI:L100I, K103N, V106A/M, V108I, Y181C/I, Y188C/L/H, G190anyA/S 8. Alcohol or substance abuse problems or psychiatric conditions that impair the ability of the subject to comply with the study protocol Inclusion Criteria: 1. Eligible subjects will be antiretroviral naïve (< 7 days of HAART at any time prior to entry) with plasma HIV-1 RNA > 50,000 copies/mL (obtained within 90 days prior to study entry by any laboratory that has a CLIA certification or its equivalent) and moderate immune suppression within 90 days prior to study entry. --- M41L --- --- D76N --- --- T69D --- --- K70R --- --- L74V --- --- Q151M --- --- M184V --- --- L210W ---
Exclusion Criteria: 1. Menopausal (may affect quantity of genital tract secretions) or any serious illness that requires treatment and/or hospitalization until the patient completes therapy 2. Any active infection, including co-infection with hepatitis B or C 3. Any neoplasm 4. Immunosuppressive therapy 5. Requirement for any medications that are prohibited by any of the study treatments 6. Significant liver or renal dysfunction 7. Baseline resistance to any of the study drugs by genotypic testing - NRTI: M41L, K65 R, D76N, T69D, K70R, L74V/I, y115F, Q151M, M184V, L210W, T215any, K219Q/E - NNRTI:L100I, K103N, V106A/M, V108I, Y181C/I, Y188C/L/H, G190anyA/S 8. Alcohol or substance abuse problems or psychiatric conditions that impair the ability of the subject to comply with the study protocol HIV-1 Infections This is a phase III, prospective, randomized (1:1), multicenter, open label study comparing the effects of two HAART regimens: - Arm A: Raltegravir 400 mg PO BID + TDF/FTC (Truvada, 300/200 mg) One PO Daily - Arm B: Efavirenz + TDF/FTC (Atripla) Once PO Daily The following local sites: Mt. --- M41L --- --- D76N --- --- T69D --- --- K70R --- --- L74V --- --- Q151M --- --- M184V --- --- L210W ---
Primary Outcomes
Measure: Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization) Time: 48 weeksMeasure: Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract Time: 48 weeks
Measure: Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine profiles Time: 48 weeks
Secondary Outcomes
Measure: Determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz Time: 48 weeks7 A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Abacavir/Lamivudine (ABC/3TC) Plus a Third Antiretroviral Agent to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed HIV 1 Infected Adult Subjects
The primary objective of this study is to evaluate the efficacy of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) relative to continuing on a baseline regimen consisting of abacavir/lamivudine (ABC/3TC) plus a 3rd antiretroviral agent in HIV-1 infected participants.
NCT02605954 HIV-1 Infection Drug: E/C/F/TAF Drug: ABC/3TC Drug: Third Antiretroviral Agent MeSH:Infection
- All documented historical plasma genotype(s) must not show resistance to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC), including, but not limited to the presence of reverse transcriptase resistance mutants K65R, K70E, M184V/I, or thymidine analog associated mutations (TAMs) (TAMs are: M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). --- K65R --- --- K70E --- --- M184V --- --- M41L --- --- D67N --- --- K70R --- --- L210W ---
Primary Outcomes
Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Measure: Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24 Time: Week 24Secondary Outcomes
Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 12 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Measure: Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12 Time: Week 12Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Measure: Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 48 Time: Week 48Measure: Change From Baseline in CD4+ Cell Count at Week 24 Time: Baseline; Week 24
Measure: Change From Baseline in CD4+ Cell Count at Week 48 Time: Baseline; Week 48
8 A Phase 3b Open-Label Pilot Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) in Virologically-Suppressed HIV-1 Infected Adult Subjects Harboring the Archived Isolated NRTI Resistance Mutation M184V/M184I
The primary objective of the study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) after switching from a stable regimen consisting of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) plus a third antiretroviral (ARV) agent in participants harboring the archived nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance mutation M184V and/or M184I in human immunodeficiency virus (HIV) -1 reverse transcriptase. This is a two part study. If the rate of virologic failure in Part 1 is deemed acceptable, once the internal data monitoring committee officially completes the interim review, the study will continue to Part 2.
NCT02616029 HIV-1 Infection Drug: E/C/F/TAF
- Proviral deoxyribonucleic acid (DNA) test must not have additional exclusion resistance mutations against PIs, NRTIs and INSTIs - Part 1: Historical genotype report must show mutation M184V and/or M184I in reverse transcriptase WITHOUT any other NRTI resistance mutation (including thymidine analogue-associated mutations [TAMs] [TAMs are: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E/N/R], K65R, K70E, T69 insertion, and Q151M mutation complex [A62V, V75I, F77L, F116Y, Q151M]) - Part 2 (after the interim efficacy review): Historical genotype report must show M184V and/or M184I in reverse transcriptase WITH or WITHOUT 1 or 2 TAMs. --- M184V --- --- M184I --- --- M41L --- --- D67N --- --- K70R --- --- L210W ---
Primary Outcomes
Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 12 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.
Measure: Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 12 as Defined by Pure Virologic Response (PVR) Time: Week 12Secondary Outcomes
Description: Development of new resistance mutations was assessed in participants who developed virologic failure, defined as 2 consecutive HIV-1 RNA result ≥ 50 copies/mL at any point in the study or with HIV-1 RNA ≥ 50 copies/mL at last visit.
Measure: Percentage of Participants With Emergence of New Mutations in HIV-1 Reverse Transcriptase and Integrase Time: Day 1 up to 48 weeksDescription: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 24 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using PVR Time: Week 24Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 48 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using PVR Time: Week 48Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 71 and 98 (inclusive).
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the FDA Snapshot Analysis Time: Week 12Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 24 window was between Day 141 and 210 (inclusive).
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the FDA Snapshot Analysis Time: Week 24Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 295 and 378 (inclusive).
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA Snapshot Analysis Time: Week 48Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 12 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 71 and 98 (inclusive).
Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 12 Using the FDA Snapshot Analysis Time: Week 12Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 24 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 24 window was between Day 141 and 210 (inclusive).
Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 24 Using the FDA Snapshot Analysis Time: Week 24Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 48 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 295 and 378 (inclusive).
Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 Using the FDA Snapshot Analysis Time: Week 48Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the Missing = Failure (M = F) Approach Time: Week 12Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the M = F Approach Time: Week 24Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = F Approach Time: Week 48Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the Missing = Excluded (M = E) Approach Time: Week 12Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the M = E Approach Time: Week 24Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach Time: Week 48Measure: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 12 Time: Baseline (Day 1); Week 12
Measure: Change From Baseline in CD4+ Cell Count at Week 24 Time: Baseline (Day 1); Week 24
Measure: Change From Baseline in CD4+ Cell Count at Week 48 Time: Baseline (Day 1); Week 48
Measure: Change From Baseline in CD4 Percentage (%) at Week 12 Time: Baseline (Day 1); Week 12
Measure: Change From Baseline in CD4 % at Week 24 Time: Baseline (Day 1); Week 24
Measure: Change From Baseline in CD4 % at Week 48 Time: Baseline (Day 1); Week 48
9 A Phase 3b, Randomized, Open-Label Study to Evaluate Switching From a Tenofovir Disoproxil Fumarate (TDF) Containing Regimen to Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Infected Subjects Aged ≥ 60 Years
The primary objective of this study is to evaluate the safety of elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (E/C/F/TAF) relative to unchanged current antiretroviral therapy (ART) by assessing spine and hip bone mineral density (BMD) measured at Week 48 in virologically-suppressed, HIV-1 infected participants aged ≥ 60 years.
NCT02616783 HIV-1 Infection Drug: E/C/F/TAF Drug: TDF Drug: FTC Drug: FTC/TDF Drug: 3TC Drug: Third agent MeSH:Infection
- Plasma HIV-1 RNA level < 50 copies/mL at screening visit - Adequate renal function - Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula (eGFRCG) and are on ARVs that are appropriately dose adjusted for renal function per package insert - All documented historical plasma genotype(s) must not show resistance to TDF or FTC, including, but not limited to the presence of reverse transcriptase resistance mutations K65R, K70E, M184V/I, or thymidine analog-associated mutations (TAMs) that include M41L, L210W, D67N, K70R, T215Y/F, K219Q/E/N/R. --- K65R --- --- K70E --- --- M184V --- --- M41L --- --- L210W ---
Primary Outcomes
Measure: Percent Change From Baseline to Week 48 in Spine BMD Time: Baseline; Week 48Measure: Percent Change From Baseline to Week 48 in Hip BMD Time: Baseline; Week 48
Secondary Outcomes
Measure: Percent Change From Baseline to Week 24 in Spine BMD Time: Baseline; Week 24Measure: Percent Change From Baseline to Week 24 in Hip BMD Time: Baseline; Week 24
Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm Time: Week 24Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm Time: Week 48Measure: Change From Baseline in CD4+ Cell Count at Week 24 Time: Baseline; Week 24
Measure: Change in Baseline in CD4+ Cell Count at Week 48 Time: Baseline; Week 48
10 A Phase 3b Randomized, Open-label, Controlled Study of the Efficacy, Safety and Tolerability of 12 Weeks of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Subjects Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment, the HIV/HCV Co-STARs Study (Co-infection Treatment With Single Tablet Antiviral Regimens)
This study will evaluate efficacy of ledipasvir/sofosbuvir (LDV/SOF) and safety and tolerability of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or emtricitabine/rilpivirine/tenofovir alafenamide (F/R/TAF) from the current antiretroviral (ARV) therapy and in virologically-suppressed, HIV-1/HCV co-infected participants.
NCT02707601 HIV-1 Infection HCV Infection Drug: E/C/F/TAF Drug: F/R/TAF Drug: LDV/SOF MeSH:Infection Communicable Diseases Hepatitis C
- Plasma HIV-1 RNA level < 50 copies/mL at the screening visit - Have no documented resistance to any of the HIV study agents at time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I, or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). --- K65R --- --- K70E --- --- K101E --- --- E138A --- --- V179L --- --- Y181C --- --- M184V --- --- Y188L --- --- H221Y --- --- F227C --- --- M230I --- --- M41L --- --- L210W ---
- Plasma HIV-1 RNA level < 50 copies/mL at the screening visit - Have no documented resistance to any of the HIV study agents at time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I, or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). --- K65R --- --- K70E --- --- K101E --- --- E138A --- --- V179L --- --- Y181C --- --- M184V --- --- Y188L --- --- H221Y --- --- F227C --- --- M230I --- --- M41L --- --- L210W --- --- M41L --- --- D67N --- --- K70R --- --- L210W ---
Primary Outcomes
Description: Sustained Virologic Response (SVR12) was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.
Measure: Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12) Time: HCV Posttreatment Week 12Secondary Outcomes
Description: SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping LDV/SOF treatment.
Measure: Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4) Time: HCV Posttreatment Week 4Description: The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm Time: 24 weeks after start of HIV treatmentMeasure: Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment Time: Up to 32 weeks plus 30 days
11 A Phase 4, Randomized, Open Label, Controlled Study of Boosted Darunavir and Lamivudine Versus Boosted Darunavir and Emtricitabine/Tenofovir or Lamivudine/Tenofovir in Naïve HIV-1 Infected Subjects
The purpose of this study is to compare the safety and efficacy of a combination of a QD regimen consisting on ritonavir boosted darunavir (FDC) and lamivudine versus ritonavir boosted darunavir (FDC) plus co-formulated tenofovir and emtricitabine or co-formulated tenofovir/lamivudine in naïve HIV-1 infected patients. Subjects will be ARV-naïve HIV-1-infected patients eligible to start ARV therapy according to current guidelines.Subjects will be adults ≥ 18 years of age who meet all of the inclusion criteria and none of the exclusion criteria.
NCT02770508 HIV-1 Infection Drug: darunavir/ritonavir Drug: Lamivudine Drug: emtricitabine-tenofovir(FTC/TDF)
- Any of the following mutations will be considered resistance to TDF: K65R, K70E, double insertion 69 or 3 TAMS including M41L or L210W. --- K65R --- --- K70E --- --- M41L --- --- L210W ---
Primary Outcomes
Description: The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) <50 c/mL at Week 48 will be assessed using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks).
Measure: Percentage of patients with HIV-1 RNA levels of less than 50 copies/mL at week 48 Time: 48 weeksSecondary Outcomes
Description: The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) <400 c/mL at Week 24 will be assessed using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm.
Measure: Percentage of patients with HIV-1 RNA <400 copies/mL at week 24 Time: 24 weeksDescription: An genotiping test will be made at time to virological failure to detect mutation across reverse transcriptase (RT), and Protease (PRO). Protocol defined virological failure was defined as confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 or confirmed plasma HIV-1 RNA levels >=50 copies/mL at week 48
Measure: Number and type of resistance mutations in case of virologic failure Time: from week 24 to week 48Description: Change from Baseline in CD4+ cell counts will be assessed at Weeks 24 and 48.
Measure: CD4+ lymphocyte count and change between baseline (defined as the average between screening and baseline visit values) and weeks 24 and 48 Time: week 24 and 48Description: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Measure: Frequency, type and severity of adverse events and laboratory abnormalities. Time: week 24 and 48Description: Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline (BS) to a CDC CAT C event (EV); CDC CAT B at BS to a CDC CAT C EV; CDC CAT C at BS to a new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.
Measure: Clinical disease progression (CDP) Time: week 24 and 48Description: The evaluation of quality of life will be done through two validated instruments: the Medical Outcomes Study HIV Health Survey ( MOS - HIV) and EuroQol 5D (EQ - 5D ) . Both instruments will be administered to patients at baseline , week 24 and week 48 .
Measure: Changes in quality of life Time: baseline, week 24 and week 4812 A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching From a Regimen of Two Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) Plus a Third Agent to a Fixed Dose Combination (FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), in Virologically-Suppressed, HIV-1 Infected African American Participants
The primary objective of this study is to evaluate the efficacy of switching from a regimen of 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and a third agent to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing their baseline regimen in HIV-1 infected, virologically suppressed African American participants.
NCT03631732 HIV-1 Infection Drug: B/F/TAF Drug: NRTIs Drug: Third Agent
- History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT substitutions are allowed, with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT will be excluded. --- M184V --- --- M41L --- --- D67N --- --- K70R --- --- L210W ---
- Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen for a minimum period of 6 months and at least the last two HIV-1 RNA measurements prior to the Screening visit - HIV-1 RNA levels < 50 copies/mL at Screening - Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance Key Exclusion Criteria: - History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT - No desire to switch from current antiretrovirals (ARVs) - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening - Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding) - Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) - Current alcohol or substance use judged by the Investigator to potentially interfere with participant study compliance - Active, serious infections (other than HIV-1 infection) requiring antibiotic or antifungal therapy within 30 days prior to Day 1 - Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial - Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with the dosing requirements - Known hypersensitivity to FDC of B/F/TAF tablets, their metabolites, or formulation excipient - Females who are pregnant (as confirmed by positive serum pregnancy test) - Females who are breastfeeding - Acute hepatitis in the 30 days prior to randomization - Active tuberculosis infection Note: Other protocol defined Inclusion/Exclusion criteria may apply. --- M41L --- --- D67N --- --- K70R --- --- L210W ---
Primary Outcomes
Measure: Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm Time: Week 24Secondary Outcomes
Measure: Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm Time: Week 48Measure: Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm Time: Week 24
Measure: Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm Time: Week 48
Measure: Change From Baseline in CD4+ Cell Count at Week 24 Time: Baseline; Week 24
Measure: Change From Baseline in CD4+ Cell Count at Week 48 Time: Baseline; Week 48