SNPMiner Trials (Home Page)
Report for Mutation L74I
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 4 clinical trials
Clinical Trials
1 A Phase IIIB, Randomized Trial of Open-Label Efavirenz or Atazanavir With Ritonavir in Combination With Double-Blind Comparison of Emtricitabine/Tenofovir or Abacavir/Lamivudine in Antiretroviral-Naive Subjects
Currently, the preferred anti-HIV regimens used in the United States consist of two nucleoside reverse transcriptase inhibitors (NRTIs) and the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV). However, with new anti-HIV drugs being approved, alternative regimens need to be tested to determine if new drug combinations have increased effectiveness in treating HIV. The purpose of this study is to test the safety, tolerability, and effectiveness of four different regimens in HIV-infected adults who have never taken anti-HIV drugs.
NCT00118898 HIV Infections Drug: Abacavir/Lamivudine Drug: Atazanavir Drug: Efavirenz Drug: Emtricitabine/Tenofovir disoproxil fumarate Drug: Ritonavir Drug: Abacavir/Lamivudine placebo Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo MeSH:HIV Infections
Major mutations were defined by International AIDS Society-United States of America (2008), as well as T69D, L74I, G190C/E/Q/T/V for reverse transcriptase and L24I, F53L, I54V/A/T/S, G73C/S/T/A, N88D for protease.. Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events.. AIDS-defining illnesses were defined per CDC category C definition. --- T69D --- --- L74I ---
Primary Outcomes
Description: Blood samples for determining virologic failure were obtained at visit weeks 16 and 24 , and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks after randomization and before 24 weeks, or >=200 copies/mL at or after 24 weeks. The 5th percentile for time to virologic failure is the time (in weeks) at which 5% of the participants have experienced virologic failure.
Measure: Time From Randomization to Virologic Failure Time: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Grade 3/4 safety event is defined as a grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline, total bilirubin and creatine kinase (CPK) were excluded. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.
Measure: Time From Treatment Dispensation to a Grade 3/4 Safety Event Time: All follow-up while on initially assigned regimen; the median (25th, 75th percentile) follow-up while on initial regimen was 120 (54, 156) weeks and the range was 0 to 205 weeks.Description: Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Time From Treatment Dispensation to Treatment Modification Time: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsSecondary Outcomes
Description: Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks. Treatment modification was defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) Time: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsMeasure: The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL Time: At Weeks 48 and 96
Measure: Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL Time: At Weeks 48 and 96
Description: Change was calculated as the CD4 count at Week 48 (or at Week 96) minus the baseline CD4 count (mean of pre-entry and entry values).
Measure: Change in CD4 Count (Cells/mm3) From Baseline Time: At Weeks 48 and 96Description: Emergence of resistant virus was assessed by genotypic testing performed at Stanford University for all participants who met criteria for virologic failure and retrospectively on baseline samples from these participants. Major mutations were defined by International AIDS Society-United States of America (2008), as well as T69D, L74I, G190C/E/Q/T/V for reverse transcriptase and L24I, F53L, I54V/A/T/S, G73C/S/T/A, N88D for protease.
Measure: Number of Participants With Virologic Failure and Emergence of Major Resistance Time: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: AIDS-defining illnesses were defined per CDC category C definition. HIV-1 related events were defined per CDC category B definition. Events underwent study chair review for classification. See link below for more details. http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm
Measure: Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. Time: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Only fasting results are included. The protocol did not require that samples be collected fasting.
Measure: Change in Fasting Total Cholesterol Level From Baseline Time: At Weeks 48 and 96Description: Only fasting results are included. The protocol did not require that samples be collected fasting.
Measure: Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline Time: At Weeks 48 and 96Description: Only fasting results are included. The protocol did not require that samples be collected fasting.
Measure: Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline Time: At Weeks 48 and 96Description: Only fasting results are included. The protocol did not require that samples be collected fasting.
Measure: Change in Fasting Triglyceride Level From Baseline Time: At Weeks 48 and 96Other Outcomes
Description: Participants were to be followed for 96 weeks after the last enrollment. Accrual was expected to take 96 weeks, thus the planned follow-up time was 96 to 192 weeks, dependent on when in the study the participant enrolled. This outcome summarizes that total amount of actual follow-up in weeks from randomization to last contact.
Measure: Amount of Study Follow-up Time: Follow-up time was variable, median follow-up was 138 weeksDescription: Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks.
Measure: Number of Participants With Virologic Failure Time: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks.
Measure: Cumulative Probability of Not Experiencing Virologic Failure Time: At week 48 and 96Description: Grade 3/4 safety event is defined as a grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline, total bilirubin and creatine kinase (CPK) were excluded. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables. As-treated analysis censored at 1st modification of initially assigned regimen, participants who never started treatment were excluded.
Measure: Number of Participants With a Grade 3/4 Safety Event Time: Over all study follow-up while on initially assigned treatment, median follow-up was 120 weeksDescription: Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. Grade 3/4 safety event is defined as a grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline, total bilirubin and creatine kinase (CPK) were excluded. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables. As-treated analysis censored at 1st modification of initially assigned regimen, participants who never started treatment were excluded.
Measure: Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event Time: At week 48 and 96Description: Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Number of Participants With Treatment Modification Time: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Cumulative Probability of Not Experiencing Treatment Modification Time: At week 48 and 96Description: Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks. Treatment modification was defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Number of Participants With Regimen Failure Time: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks. Treatment modification was defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Cumulative Probability of Not Experiencing Regimen Failure Time: At week 48 and 962 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
- No mutation (either on pre-ART genotype or on DNA genotype at screening) among the following: T66K, G118R, V151L, S153F/Y, R263K, T66K + L74M, E92Q + N155H, Q148R +N155H, Q148H/K/R with at least one mutation of L74I or E138A/K/T or G140A/C/S - Negative HBs Ag - Informed consent form signed by patient and investigator - A specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the Dolutegravir + Rilpivirine arm and will volunteer for this PK study - Patient covered with health insurance - Effective contraception Exclusion Criteria: - HIV-2 infection - Dialysis or severe renal failure (creatinine clearance < 30 ml/min) - History of decompensated liver disease - History of HIV-associated neurocognitive disorders - AST or ALT > 5 x ULN - Positive HBc Ac and negative HBs Ac - Patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug - Current pregnancy or breastfeeding - Patient involved in another research that precludes enrolment in another trial - Patient under guardianship, or deprived of liberty by a court or administrative decision. --- T66K --- --- G118R --- --- V151L --- --- S153F --- --- R263K --- --- T66K --- --- L74M --- --- E92Q --- --- N155H --- --- Q148R --- --- Q148H --- --- L74I ---
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 16Measure: 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 48Measure: 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: W48Description: 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 24Description: 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 48Description: 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 48Description: 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 24Description: 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 48Description: 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 24Description: 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 48Description: 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 24Description: 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 48Description: Assessment of patient satisfaction for their treatment at D0 by questionnaire
Measure: Measure of patient satisfaction for their treatment at Day 0 Time: Day 0Description: 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 24Description: 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 48Description: 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 24Description: 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 48Description: 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 4Description: 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 24Measure: 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
3 Darunavir/Cobicistat and Dolutegravir to Maintain Virologic Suppression and Reduce NRTI-associated Toxicity (The 'deNUC' Study; TMC114HIV2030)
This is a clinical research study to see if switching to Darunavir/Cobicistat ((PREZCOBIX™, DRV/COBI ) and Dolutegrivir (Tivicay®, DTG) in HIV-infected individuals with undetectable HIV viral load on nucleos(t)ide reverse transcriptase inhibitor (NRTI)-containing therapy will be effective in maintaining virologic suppression at 48 weeks of treatment.
NCT02499978 HIV/AIDS Drug: Darunavir/Cobicistat Drug: Dolutegravir
Prohibited protease mutations: V11I, V32I, L33F, I47V/A/L, I50V, I54T/S/L/M, T74P, L76V, V82F, I84V, or L89V Prohibited INSTI mutations: E92Q, E92K/A, G140S/A/C, Q148H/R/K or Q148 substitution plus any of the following: L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54T --- --- T74P --- --- L76V --- --- V82F --- --- I84V --- --- L89V --- --- E92Q --- --- E92K --- --- G140S --- --- Q148H --- --- L74I ---
Primary Outcomes
Description: Compare between arms the proportion of patients maintaining virologic suppression (i.e., no confirmed HIV RNA levels ≥200 copies/mL) at Week 24
Measure: Virologic suppression (24 weeks) Time: 24 weeksSecondary Outcomes
Description: Evaluate the proportion of participants who maintain virologic suppression 24 weeks post-switch (i.e. at 24 weeks in the immediate switch arm and at 48 weeks in the delayed switch arm)
Measure: Virologic Suppression (48 weeks) Time: 48 weeks4 Drug-Drug Interactions Between Rifapentine and Dolutegravir in HIV/LTBI Co-Infected Individuals
This study will evaluate the potential drug-drug interactions between dolutegravir (DTG) and steady state rifapentine (RPT) when RPT is given with isoniazid (INH) daily for 4 weeks (1HP) as part of treatment for latent TB infection (LTBI) in HIV-1 and LTBI co-infected individuals.
NCT04272242 HIV Infection LTBI Drug: Dolutegravir (DTG) Drug: Isoniazid (INH) Drug: Rifapentine (RPT) Drug: Antiretroviral Therapy (ART) Dietary Supplement: Pyridoxine (Vitamin B6) MeSH:Infection HIV Infections
This includes the following INSTI mutations: Q148 substitutions, T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, G193E/R, or N155H. --- T66A --- --- L74I ---
Primary Outcomes
Measure: DTG PK Parameter Maximum Plasma Concentration (Cmax) by visit week and arm Time: Measured at Days 0 and 28Measure: DTG PK Parameter Area Under the Curve (AUC0-12 for BID & AUC0-24 for QD dosing) by visit week and arm Time: Measured at Days 0 and 28
Measure: DTG PK Parameter Minimum Plasma Concentration (Cmin) by visit week and arm Time: Measured at Days 0 and 28
Secondary Outcomes
Description: Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017
Measure: Proportion of participants with all adverse events meeting the reporting criteria in the study protocol during administration of DTG with 1HP, by arm Time: Measured through Week 4Measure: Proportion of participants who discontinue study or study drugs during DTG and 1HP dosing, by arm Time: Measured through Week 4
Measure: Proportion of participants with HIV-1 RNA levels >50 copies/mL Time: Measured at Days 28 and 42