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Report for Mutation Y115F
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 6 clinical trials
Clinical Trials
1 See Detailed Description
This study was designed to test the efficacy, safety, tolerability and durability of the antiviral response between atazanavir (ATV) + ritonavir (/r) + abacavir/lamivudine(ABC/3TC) Fixed dose combination (FDC) each administered once daily (QD) for 36 weeks followed by randomization to either a simplification regimen of ATV or continuation of ATV +/r for an additional 48 weeks, each in combination with ABC/3TC in antiretroviral (ART)-naive, HIV-1 infected, HLA-B*5701 negative subjects. All subjects who complete the 84-week study will be eligible to enter the treatment extension phase and continue for an additional 60 weeks. The purpose of this extension is to obtain longer term treatment data in subjects who have completed the 84-week study.
NCT00440947 Infection, Human Immunodeficiency Virus I HIV Infection Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r) Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) MeSH:Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome
- Subject testing positive for Hepatitis B or both Hepatitis B and Hepatitis C at screening (+ HbsAg) - Genotyping results performed at the screening indicate that the subject has any of the following mutations at the reverse transcriptase (RT) enzyme: K65R, L74V, or Y115F, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, or ≥ 3 of the following protease mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50, I54, A71, G73, V77, V82, I84, N88, and L90. - Women who are pregnant or breastfeeding. --- K65R --- --- L74V --- --- Y115F ---
Primary Outcomes
Description: The percentage of PAR with HIV-1 RNA virus <50 c/ml determined from a blood sample drawn at Week 84 was tabulated by treatment arm with stratification by baseline HIV-1 RNA (<100,000 c/ml and >=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed viral load <50 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <50 c/ml, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 50 c/ml, or had an unconfirmed HIV RNA of at least 50 c/ml at last visit.
Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c) /Milliliter (ml) at the Week 84 Visit Time: Week 84Secondary Outcomes
Description: The mean age of participants randomized to treatment in the Randomized Phase was calculated at Baseline.
Measure: Mean Age at Baseline of Participants Randomized to Treatment for the 48-Week Randomized Phase Time: Baseline of Randomized PhaseDescription: The percentage of PAR with HIV-1 RNA virus <50 c/ml from a Week 36 blood sample was tabulated. Per TLOVR algorithm, responders were PAR with confirmed viral load <50 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <50 c/ml, prematurely discontinued (DC) study or study medication (any reason), had confirmed rebound to >=50 c/ml, or had an unconfirmed HIV RNA >=50 c/ml at last visit. ITT-E observed analysis (Obs): all observed data. ITT-E M/D=F analysis: PAR with missing data/data collected after study medication DC were failures.
Measure: Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 36 Visit Time: Week 36Description: A blood sample was drawn to determine the amount of HIV-1 RNA virus in c/ml at Week 84. The percentage of participants with HIV-1 RNA <50 c/ml at Week 84 was tabulated. The secondary analysis methods were: Observed (Obs; uses all visits with data in the analysis period), and missing/discontinuation=failure (M/D=F) analyses. M/D=F: participants with missing data or data collected after study medication DC were considered failures.
Measure: Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 84 Visit Time: Week 84Description: Percentage of PAR with HIV-1 RNA <50 c/ml at Week 144 was tabulated; stratified by baseline HIV-1 RNA (<100,000 and >=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV RNA <50 c/ml who had not met any non-responder (NR) criterion. NR were PAR who never achieved CF HIV RNA <50 c/ml, prematurely discontinued (DC) study or study medication (Med), had CF rebound to >=50 c/ml, or had an unconfirmed HIV RNA >=50 c/ml at last visit. Observed analysis (Obs): all observed data. M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.
Measure: Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 144 Visit Time: Week 144Description: The percentage of PAR with HIV-1 RNA virus <400 c/ml from a Week 36 blood sample was tabulated. Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV RNA <400 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved CF HIV RNA <400 c/ml, prematurely discontinued (DC) study or study medication (Med; any reason), had CF rebound to >=400 c/ml, or had an unconfirmed HIV RNA >=400 c/ml at last visit. ITT-E observed analysis (Obs): all observed data. ITT-E M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.
Measure: Percentage of Participants Who Achieved Plasma HIV-1 RNA <400 c/ml at the Week 36 Visit Time: Week 36Description: Percentage of PAR with HIV-1 RNA <400 c/ml at Week 84 was tabulated; stratified by baseline HIV-1 RNA (<100,000 and >=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV-RNA <400 c/ml who had not met any non-responder (NR) criterion. NR were PAR who never achieved CF HIV RNA <400 c/ml, prematurely discontinued (DC) study or study medication (Med), had CF rebound to >=400 c/ml, or had an unconfirmed HIV RNA >=400 c/ml at last visit. Observed analysis (Obs): all observed data. M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.
Measure: Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 84 Visit Time: Week 84Description: Percentage of PAR with HIV-1 RNA <400 c/ml at Week 144 was tabulated; stratified by baseline HIV-1 RNA (<100,000 and >=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV-RNA <400 c/ml who had not met any non-responder (NR) criterion. NR were PAR who never achieved CF HIV RNA <400 c/ml, prematurely discontinued (DC) study or study medication (Med), had CF rebound to >=400 c/ml, or had an unconfirmed HIV RNA >=400 c/ml at last visit. Observed analysis (Obs): all observed data. M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.
Measure: Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 144 Visit Time: Week 144Description: The number of participants that failed to respond to therapy through 36 weeks on treatment, based on the protocol definition of virologic failure (PDVF), was tabulated. PDVF was defined as (a) failure to achieve plasma HIV-1 RNA <400 c/ml by Week 30 or (b) confirmed HIV-1 RNA rebound >=400 c/ml after achieving HIV-1 <400 c/ml.
Measure: Number of Participants Who Met the Protocol-defined Virologic Failure (PDVF) Criteria at Week 36 Time: Week 36Description: The number of participants that failed to respond to therapy from the time of treatment randomization through Week 84, based on the protocol definition of virologic failure (PDVF), was tabulated. PDVF was defined as (a) failure to achieve plasma HIV-1 RNA <400 c/ml by Week 30 or (b) confirmed HIV-1 RNA rebound >=400 c/ml after achieving HIV-1 <400 c/ml.
Measure: Number of Participants Who Met the PDVF Criteria at Week 84 Time: Week 84Description: The number of participants enrolled in the extension phase that failed to respond to therapy from Week 84 through Week 144, based on the protocol definition of virologic failure (PDVF) was tabulated,. PDVF was defined as (a) failure to achieve plasma HIV-1 RNA <400 c/ml by Week 30 or (b) confirmed HIV-1 RNA rebound >=400 c/ml after achieving HIV-1 <400 c/ml.
Measure: Number of Participants Who Met the PDVF Criteria at Week 144 Time: Week 144Description: Change from baseline was calculated as the Week 36 value minus the baseline value. Blood was drawn to analyze for plasma HIV viral load.
Measure: Change From Baseline in HIV-1 RNA at Week 36 Time: Baseline and Week 36Description: Change from baseline was calculated as the Week 84 value minus the baseline value. Blood was drawn to analyze for plasma HIV viral load.
Measure: Change From Baseline in HIV-1 RNA at Week 84 Time: Baseline and Week 84Description: Change from baseline was calculated as the Week 144 value minus the baseline value. Blood was drawn to analyze for plasma HIV viral load.
Measure: Change From Baseline in HIV-1 RNA at Week 144 Time: Baseline and Week 144Description: Blood was drawn to analyze for CD4+ cell count. A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from baseline was calculated as the Week 36 value minus the baseline value.
Measure: Change From Baseline in CD4+ Cell Count at Week 36 Time: Baseline and Week 36Description: A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from baseline was calculated as the Week 84 value minus the baseline value. Blood was drawn to analyze for CD4+ cell count.
Measure: Change From Baseline in CD4+ Cell Count at Week 84 Time: Baseline and Week 84Description: A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from baseline was calculated as the Week 144 value minus the baseline value. Blood was drawn to analyze for CD4+ cell count.
Measure: Change From Baseline in CD4+ Cell Count at Week 144 Time: Baseline and Week 144Description: A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New resistance-associated mutations (defined by the International AIDS Society-USA guidelines) that developed at the time of failure were tabulated by drug class. PAR, participants; VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Measure: Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 36 Time: Baseline through Week 36Description: A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDs Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Measure: Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Randomization at Week 36 Through Week 84 Time: Randomization at Week 36 through Week 84Description: A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDs Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Measure: Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Week 84 Through Week 144 Time: Week 84 through Week 144Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at baseline. PAR, participant.
Measure: Number of Confirmed Virologic Failure Participants From Baseline Through Week 36 With Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir Time: Baseline through Week 36Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at baseline. PAR, participant.
Measure: Number of Confirmed Virologic Failure Participants From Randomization at Week 36 Through Week 84 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir Time: Randomization at Week 36 through Week 84Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at baseline. PAR, participant.
Measure: Number of Confirmed Virologic Failure Participants From Week 84 Through Week 144 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir Time: Week 84 through Week 144Description: Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.
Measure: Mean Percent Compliance at Week 36 Time: Week 36Description: Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.
Measure: Mean Percent Compliance at Week 84 Time: Week 84Description: Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.
Measure: Mean Percent Compliance at Week 144 Time: Week 1442 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 ---
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 days3 A Study in Underrepresented Patient Population or Regimen Tolerability: SUPPoRT
The hope of this study is to gather data and information about the tolerability and effectiveness of Lexiva versus Sustiva in patients who have have been generally underrepresented in clinical trials.
NCT00727597 Human Immunodeficiency Virus Infections Drug: Efavirenz 600mg Drug: Boosted Lexiva MeSH:Acquired Immunodeficiency Syndrome HIV Infections
v. Sterilization (female subject or male partner of female subject) Exclusion Criteria: Screening HIV-1 genotype indicating the presence of any of the following mutations in the reverse transcriptase (RT) region: K65R, L74V, K103N, Y115F, Y181C/I, Y188C/L/H or G190S/A, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, associated with resistance to abacavir, lamivudine, or efavirenz; OR within the protease region, detection of any of the following mutations associated with resistance to fosamprenavir or ritonavir: I50V, I54L/M, I84V, or the combination of the two mutations V32I+I147V Positive for Hepatitis B surface antigen (HBsAg+) Requirement for active treatment for hepatitis C virus infection, as indicated by both a positive Hepatitis C Virus serology AND either: 1. Decompensated liver disease, or 2. Aspartate aminotransferase (AST) >3X the upper limit of normal (ULN), or 3. Alanine aminotransferase (ALT) >3X the ULN Currently pregnant, intending to become pregnant during the study period, or breast-feeding Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), any vaccinations, systemic cytotoxic chemotherapy, or investigational therapy within 28 days prior to study entry. --- K65R --- --- L74V --- --- K103N --- --- Y115F ---
Primary Outcomes
Description: Subjects were randomized and initiated treatment on one of the antiretroviral arms(FPV/r or EFV) at study Entry visit. Subjects would be switched for the follwing reasons: To resolve a Grade 3 or 4 Adverse Event The subject experienced a virologic failure (as defined in section 3.6.2) The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide)
Measure: Number of Subjects Needing to Switch Comparator Drugs (FPV/r or EFV) Time: 96 weeksMeasure: Number of Subjects Developing Any Treatment-related Grade 3-4 Adverse Events Time: 96 weeks
4 A Pilot Study of Highly Active Antiretroviral Therapy Using Isentress (Raltegravir) and Epzicom (Abacavir/Lamivudine) in Antiretroviral Naive HIV-Infected Subjects
To evaluate the efficacy and safety of Raltegravir and Epzicom over 48 weeks in ART-naive HIV-infected subjects.
NCT00740064 HIV Infections Drug: Raltegravir and Abacavir/Lamivudine MeSH:HIV Infections
Exclusion Criteria: - Screening HIV-1 genotype indicating the presence of any of the following mutations: K65R, L74V, and Y115F or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, associated with ABC and 3TC resistance, and mutations Q148H/R/K and N155H associated with RTG resistance. --- K65R --- --- L74V --- --- Y115F ---
Primary Outcomes
Measure: To evaluate the efficacy and safety of RTG and ABC/3TC over 48 weeks in ART-naive HIV-infected subjects. Time: 48 weeksSecondary Outcomes
Measure: To assess the immunologic response, changes in fasting lipids, renal function, and development of resistance of the study regimen Time: 48 weeks5 A Prospective, Randomized, Multicenter, Open-Label Study to Compare the Efficacy and Safety of Simplifying From a Regimen of Atazanavir (ATV) + Ritonavir (RTV) + Tenofovir/Emtricitabine to ATV + Abacavir/Lamivudine Without RTV in Virologically Suppressed, HIV-1 Infected, HLA-B*5701 Negative Subjects
This study is designed to compare the efficacy and safety of simplifying therapy from a regimen of atazanavir (ATV) + ritonavir (RTV) + tenofovir/emtricitabine (TDF/FTC) to a regimen of ATV + abacavir sulfate/lamivudine (ABC/3TC) without RTV in virologically suppressed, HIV-1 infected, HLA-B*5701 negative subjects for 48 weeks.
NCT01102972 Infection, Human Immunodeficiency Virus Drug: Reyataz + Norvir + Truvada Drug: Reyataz + Epzicom MeSH:Acquired Immunodeficiency Syndrome HIV Infections
- Subject is virologically suppressed on ATV + RTV + TDF/FTC defined as HIV-1 RNA Y115F, a combination of two or more thymidine analog mutations including M41L, D67N, K70R, K219Q or E that include changes at either L210 or T215), or 3 or more of the following HIV-1 protease mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50, I54, A71, G73, V77, V82, I84, N88, and L90 - Subject is HLA-B*5701 positive - Subject has hypersensitivity to any component of the study drugs - SUbject is pregnant or breastfeeding - Subject is enrolled in one or more investigational drug protocols within 30 days of screening - Subject has an active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial - Subject has ongoing clinically relevant hepatitis at screening and/or positive for Hepatitis B (+ HbsAg) - Subject has a creatinine clearance <50 mL/min via the Cockcroft-Gault method - Subject has a verified Grade 4 laboratory abnormality at screening unless the Investigator can provide a compelling explanation (e.g. --- K65R --- --- K70E --- --- L74V --- --- M184I --- --- Y115F ---
Primary Outcomes
Description: The percentage of PAR with HIV-1 RNA virus <50 c/mL determined from blood samples drawn at Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment. Per TLOVR algorithm, responders were PAR with confirmed viral load <50 c/mL who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <50 c/mL, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 50 c/mL, or had an unconfirmed HIV RNA of at least 50 c/mL at the last visit.
Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c)/Milliliter (mL) at the Week 24 Visit: TLOVR Analysis Time: Week 24Secondary Outcomes
Description: The percentage of PAR with HIV-1 RNA virus <50 c/mL determined from blood samples drawn through Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.
Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 c/mL at the Week 24 Visit: Observed, M/D=F, and SNAPSHOT Analyses Time: Week 24Description: The percentage of PAR with HIV-1 RNA virus <50 c/mL determined from blood samples drawn at Week 48 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.
Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 c/mL at the Week 48 Visit: TLOVR, Observed, M/D=F, and SNAPSHOT Analyses Time: Week 48Description: The percentage of PAR with HIV-1 RNA virus <400 c/mL determined from blood samples drawn at Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment. Per TLOVR algorithm, responders were PAR with confirmed viral load <400 c/mL who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <400 c/mL, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 400 c/mL, or had an unconfirmed HIV RNA of at least 400 c/mL at the last visit.
Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: TLOVR Analysis Time: Week 24Description: The percentage of PAR with HIV-1 RNA virus <400 c/mL determined from blood samples drawn at Week 48 was tabulated by treatment arm with stratification by initial antiretroviral treatment. Per TLOVR algorithm, responders were PAR with confirmed viral load <400 c/mL who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA <400 c/mL, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 400 c/mL, or had an unconfirmed HIV RNA of at least 400 c/mL at the last visit.
Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: TLOVR Analysis Time: Week 48Description: The percentage of PAR with HIV-1 RNA virus <400 c/mL determined from blood samples drawn at Week 24 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.
Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: Observed, MD=F, and SNAPSHOT Analyses Time: Week 24Description: The percentage of PAR with HIV-1 RNA virus <400 c/mL determined from blood samples drawn at Week 48 was tabulated by treatment arm with stratification by initial antiretroviral treatment using specific analysis methods.
Measure: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: Observed, MD=F, and SNAPSHOT Analyses Time: Week 48Description: Change from Baseline was calculated as the Week 24 value minus the Baseline value. Blood was drawn to analyze for plasma HIV viral load.
Measure: Change From Baseline in HIV-1 RNA at Week 24 Time: Baseline and Week 24Description: Change from Baseline was calculated as the Week 48 value minus the Baseline value. Blood was drawn to analyze for plasma HIV viral load.
Measure: Change From Baseline in HIV-1 RNA at Week 48 Time: Baseline and Week 48Description: Blood was drawn to analyze for CD4+ cell count. A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from Baseline was calculated as the Week 24 value minus the Baseline value.
Measure: Change From Baseline in CD4+ Cell Count at Week 24 Time: Baseline and Week 24Description: Blood was drawn to analyze for CD4+ cell count. A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from Baseline was calculated as the Week 48 value minus the Baseline value.
Measure: Change From Baseline in CD4+ Cell Count at Week 48 Time: Baseline and Week 48Description: Triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured at Week 24. A Fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 24 value minus the Baseline value for each parameter.
Measure: Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 24 Time: Baseline and Week 24Description: A Fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 24 value minus the Baseline value.
Measure: Change From Baseline in Cholesterol/HDL Ratio at Week 24 Time: Baseline and Week 24Description: Triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured or calculated at Week 48. A fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 48 value minus the Baseline value for each parameter.
Measure: Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 48 Time: Baseline and Week 48Description: A fasting blood sample was drawn to analyze for lipids. Change from Baseline was calculated as the Week 48 value minus the Baseline value for each parameter.
Measure: Change From Baseline in Cholesterol/HDL Ratio at Week 48 Time: Baseline and Week 48Description: The number of participants that failed to remain virologically suppressed through 24 weeks on treatment was assessed. Viral failure is defined per protocol as confirmed HIV-1 RNA >=400 c/mL.
Measure: Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 24 Time: From Baseline to Week 24Description: The number of participants that failed to remain virologically suppressed from baseline through 48 weeks on treatment was assessed. Viral failure is defined per protocol as confirmed HIV-1 RNA >=400 c/mL.
Measure: Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 48 Time: From Baseline to Week 48Description: Death and clinical disease progression (as per CDC classification) were assessed from Baseline through Week 48. Disease progression is defined as progression from CDC Class A to B, Class A to C, or from Class B to C. AIDS CDC classifications are: Class A, Asymptomatic/lymphadenopathy/acute HIV; Class B, Symptomatic, not AIDS; Class C, AIDS indicator conditions. The CDC categorization of HIV/AIDS is based on the lowest documented CD4 cell count (Class A, >=500 cells per microliter [µl]; Class B, 200-499 cells/µl; Class C, <200 cells/µl) and on previously diagnosed HIV-related conditions.
Measure: Number of Participants Who Experienced Death and/or Disease Progression Time: From Baseline to Week 48Description: A blood sample was drawn for particiapants with confirmed VF >=400 c/mL. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at Baseline. New resistance-associated viral mutations defined by the International Acquired Immunodeficiency Syndrome Society-United States of America guidelines present at the time of failure were tabulated by drug class. NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Measure: Number of Confirmed Virologic Failure (VF) Participants (PAR) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 24 Time: From Baseline to Week 24Description: A blood sample was drawn for particiapants with confirmed VF >=400 c/mL. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at Baseline. New resistance-associated viral mutations defined by the International Acquired Immunodeficiency Syndrome Society-United States of America guidelines present at the time of failure were tabulated by drug class. NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Measure: Number of Confirmed Virologic Failure (VF) Participants (PAR) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 48 Time: From Baseline to Week 48Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at Baseline.
Measure: Number of Confirmed Virologic Failure Participants (PAR) From Baseline Through Week 24 With the Indicated Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Tenofovir, Emtricitabine, Atazanavir, or Ritonavir Time: From Baseline to Week 24Description: A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at Baseline.
Measure: Number of Confirmed Virologic Failure Participants (PAR) From Baseline Through Week 48 With the Indicated Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Tenofovir, Emtricitabine, Atazanavir, or Ritonavir Time: From Baseline to Week 48Description: The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 is a descriptive terminology that can be utilized for AE reporting. A grading (severity) scale is provided for each AE. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1, mild AE; Grade 2, moderate AE; Grade 3, severe AE; Grade 4, life-threatening or disabling AE; Grade 5, death related to the AE.
Measure: Number of Participants With the Indicated Grade 2 to Grade 4 Adverse Events (AEs) Occurring at a Frequency of >=3% in Either Treatment Group Time: From Baseline to Week 24Description: The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 is a descriptive terminology that can be utilized for AE reporting. A grading (severity) scale is provided for each AE. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1, mild AE; Grade 2, moderate AE; Grade 3, severe AE; Grade 4, life-threatening or disabling AE; Grade 5, death related to the AE.
Measure: Number of Participants With the Indicated Grade 2 to Grade 4 Adverse Events (AEs) Occurring at a Frequency of >=3% in Either Treatment Group Time: From Baseline to Week 486 Explorations Into the Mechanism for INSTI-associated Weight Gain: a Focus on Energy Balance
Weight gain following antiretroviral therapy (ART) initiation occurs with all modern regimens. Recent real-world reports suggest that integrase strand transfer inhibitor (INSTI)-based ART may be associated with excess weight gain compared to other regimens. Weight gain appears to occur regardless of baseline weight, and is most pronounced among women and minorities, often those at highest risk of obesity-associated comorbidities. INSTI- and TAF-based regimens are now preferred regimens for most persons according to the Department of Health and Human Services ART-Treatment Guidelines. As a result, there is an urgent need to understand the underlying mechanisms for this weight gain. This study aims to understand the changes in energy balance that occur with changes in ART. Participants with HIV who have experienced >10% weight gain on INSTI (bictegravir or dolutegravir-based therapy) will be switched to doravirine for 12 weeks, and then back to their prior INSTI regimen, allowing for assessment of changes in metabolic parameters with drug withdrawal and reintroduction (with no change to NRTI-backbone). Twenty-four hour energy balance will be measured on both regimens during a 24-hour stay using a whole room indirect calorimetry, with a standardized diet. Ultimately, the investigator's goal is to understand the mechanisms of weight gain so that future interventions can most effectively mitigate ART-associated weight changes.
NCT04495348 HIV-1-infection Weight Gain Drug: Doravirine MeSH:Body Weight Weight Gain
HPO:Increased body weight
- Severe claustrophobia that would limit ability of participant to remain in the whole room calorimeter - Known resistance to any component of the study drugs, including detection of any of the following resistance mutations on prior HIV genotype test (genotype testing not required if not available): Doravirine resistance: V106A, V106I, V106T, V106M, Y188C, Y188H, Y188L, G190E, P225H, F227C, F227L, F227R, M230L, L234I Resistance to NRTIs: K65R, K65E, K65N, T69S (insertion complex), K70E, L74V, Y115F, Q151M, M184I, M184V. --- V106A --- --- V106I --- --- V106T --- --- V106M --- --- Y188C --- --- Y188H --- --- Y188L --- --- G190E --- --- P225H --- --- F227C --- --- F227L --- --- F227R --- --- M230L --- --- L234I --- --- K65R --- --- K65E --- --- K65N --- --- T69S --- --- K70E --- --- L74V --- --- Y115F ---
Primary Outcomes
Description: Change in total energy expenditure (kcal/day)
Measure: Change in energy balance Time: 24 weeks