There are 7 clinical trials
Randomized, blinded, placebo-controlled trial to demonstrate if pre-exposure prophylaxis decreases HIV-1 acquisition among HIV-1 uninfected individuals within HIV-1 discordant couples.
HIV-1 resistance as measured by the number of seroconverters who had an HIV-1 reverse transcriptase mutation (K65R, K70E, M184I, or M184V) conferring resistance to TDF or FTC. --- K65R --- --- K70E --- --- M184I ---
Description: The efficacy of once daily PrEP in preventing HIV-1 acquisition among uninfected heterosexuals in HIV-1 discordant partnerships, measured by calculating the HIV incidence per 100 person-years in each of three arms.
Measure: Incidence of HIV-1 Seroconversion Among HIV-1 Uninfected Participants Time: Up to 36 monthsDescription: Safety of daily TDF or FTC/TDF among HIV-1 uninfected individuals randomized to TDF or FTC/TDF compared to those randomized to placebo measured as the number of participants with Serious Adverse Events (SAEs) during follow-up.
Measure: Number of Participants With Serious Adverse Events (SAEs) Time: Up to 36 monthsDescription: Adherence to study medication as assessed by pill count at follow-up visits. We assessed the total number of doses taken of the total dispensed doses.
Measure: Study Drug Adherence: Total Number of Study Drug Doses Taken of the Total Dispensed Doses. Time: Up to 36 monthsDescription: Adherence to study drug measured as the percentage of visits when participants reported missing 1) any dose of study drug in the prior month and 2) 2 or more consecutive doses of study drug.
Measure: Study Drug Adherence: Self-reported Missed Doses of Study Drug Time: Up to 36 monthsDescription: HIV-1 resistance as measured by the number of seroconverters who had an HIV-1 reverse transcriptase mutation (K65R, K70E, M184I, or M184V) conferring resistance to TDF or FTC. These mutation types were pre-defined. Plasma samples for resistance testing were collected at the visit seroconversion was first detected and again at a visit within 1 month of seroconversion. Mutations detected at either of those visits are reported. Both seroconverters found to have a resistance mutation had been HIV infected at enrollment (TDF arm: n=1; FTC-TDF arm: n=1).
Measure: Number of Seroconverters With an HIV-1 Mutation Conferring Resistance to TDF or FTC Time: Up to 36 monthsDescription: Prevalence of STIs measured as the number of participants with a positive test result for N. gonorrhoeae, C. trachomatis, or T. vaginalis during follow-up. Participants were tested for STIs at annual follow-up visits and at intervening visits at which the participant presented with symptoms of an STI. Assessment for symptomatic sexually transmitted infections was conducted quarterly. N. gonorrhoeae and C. trachomatis testing were by APTIMA Combo 2 (Gen-Probe) or COBAS Amplicor (Roche Diagnostics). T. vaginalis testing was by APTIMA TV TMA (Gen-Probe) or In Pouch TV (Biomed Diagnostics).
Measure: Number of Participants With a Sexually Transmitted Infection (STI) During Follow-up Time: Up to 36 monthsDescription: Sexual risk behavior of participants, measured as the percentage of visits when participants reported having unprotected sex during follow-up.
Measure: Prevalence of Unprotected Sex During Follow-up Time: Up to 36 monthsDescription: Infant outcomes measured as the number of live-born infants born to female participants taking study drug that had any congenital anomalies.
Measure: Congenital Abnormalities Among Infants Born to Female Participants Taking Study Drug. Time: Up to 36 monthsDescription: The slope of the linear model of the growth of infants (length) during the entirety of follow-up. The length of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.
Measure: Length Among Infants Born to Female Participants Taking Study Drug Time: up to 12 monthsDescription: The slope of the linear model of the growth of infants (weight) during the entirety of follow-up. The weight of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.
Measure: Weight Among Infants Born to Female Participants Taking Study Drug Time: up to 12 monthsDescription: The slope of the linear model of the growth of infants (head circumference) during the entirety of follow-up. The head circumference of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.
Measure: Head Circumference Among Infants Born to Female Participants Taking Study Drug Time: up to 12 monthsElvucitabine is a novel nucleoside analog that is being studied as a treatment for patients infected with HIV-1. This Phase II study will enroll 60 HIV-1 naive subjects to assess the efficacy and safety of elvucitabine compared to lamivudine in combination with tenofovir and efavirenz measured by changes in the patient's HIV-RNA level and CD4 cell count. The study treatment will be 12 weeks of blinded study medication followed by an additional 84 weeks of open label treatment if the patient's response to treatment meets certain endpoints. Also there will be assessment of the pharmacokinetics of elvucitabine during the study.
2. Are 18 through 65 years old 3. Have documented HIV-1 infection by written prior history and clinically stable with no AIDS-defining events in the 3 months prior to Screening 4. Have plasma HIV-1 RNA levels greater than or equal to 5000 copies/mL at Screening 5. Are HIV-1 strain sensitive to elvucitabine, lamivudine, emtricitabine as demonstrated by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1 Genotyping Kit 6. Are HIV-1 strain genotypically sensitive to efavirenz (negative for K103 and Y188L mutations) and tenofovir (negative for K65R mutation) by TRUGENE HIV-1 Genotyping Kit 7. Have a CD4 count greater than or equal to 200 cells/mL and less than 500 cells/mL 8. Have acceptable hematologic and chemistry parameters, including the following: - Hemoglobin (Hgb) greater than or equal to 11g/dL - Absolute neutrophil count greater than or equal to 2000 cells/mm3 - Platelets greater than or equal to 125 000/mm3 - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 1.5 times the upper limit of normal - Total bilirubin less than or equal to 1.5 times the upper limit of normal - Creatinine within normal range 9. Are capable of understanding and has signed the informed consent document 10. --- M184V --- --- M184I ---
Subjects must be sensitive to elvucitabine, lamivudine, and emtricitabine as demonstrated by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1 Genotyping Kit. --- M184V --- --- M184I ---
Description: Proportion of subjects having achieved a virologic response for elvucitabine 10 mg/day in combination with efavirenz and tenofovir in HIV-1-infected subjects over 12 weeks compared with the proportion of subjects having achieved a virologic response for lamivudine 300 mg/day in combination with efavirenz and tenofovir. Virologic response was defined as having achieved undetectable (<50 copies/mL) HIV-1 RNA levels from baseline assessment.
Measure: The Proportion of Subjects With Virologic Response for 10 mg/Day Elvucitabine in HIV-1-infected Subjects by 12 Weeks Compared With the Proportion of Subjects With Lamivudine 300 mg/Day. Time: 12 WeeksDescription: Determination of the safety profile of elvucitabine as defined by the frequency, type and severity of treatment-emergent adverse events and the frequency of Grade 3 and Grade 4 laboratory abnormalities.
Measure: The Safety Profile of Elvucitabine. Time: 12 WeeksThis study is an open-label extension of RFSP-AMDX-2010 study for those subjects who received treatment with amdoxovir (300 mg or 500 mg twice daily) for 12 weeks and benefited from it. This study will examine the safety and efficacy of the investigational HIV drug, amdoxovir (300 mg and 500 mg bid doses; N = up to 30) in combination with zidovudine and lopinavir/ritonavir for 36 weeks. Subjects will continue to receive either amdoxovir 300 mg twice daily or amdoxovir 500 mg twice daily, each in combination with zidovudine 300 mg twice daily and lopinavir/ritonavir (400 mg/100 mg twice daily) for additional 36 weeks.
An Open-label, 36-week Extension Study on Amdoxovir at 500 mg Bid or 300 mg Bid in Combination With Zidovudine and Lopinavir/Ritonavir in HIV-1 Treatment-experienced Subjects With M184I/V Mutation in Addition to 0-2 Confirmed Thymidine Analog Mutations.. --- M184I ---
This is a double-blind Phase 2a study to test the safety and efficacy of an investigational HIV drug, amdoxovir (300 mg or 500 mg twice daily) compared with tenofovir DF 300 mg once daily in HIV-1 infected antiretroviral therapy-experienced subjects who are currently failing antiretroviral therapy. There are three treatment groups (N=45). Subjects will be randomized to receive either amdoxovir 300 mg twice daily (n=15) or amdoxovir 500 mg twice daily (n=15) or tenofovir DF 300 mg once daily (n=15); each in combination with zidovudine 300 mg twice daily. The study will assess initially amdoxovir (300 mg or 500 mg twice daily) or tenofovir DF 300 mg once daily, both in combination zidovudine 300 mg twice daily plus failing third drug, but then with lopinavir/ritonavir (400 mg/100 mg twice daily) after Week 2. Subjects who received amdoxovir (300 mg or 500 mg twice daily) and benefited from the drug may choose to enroll in the 36-week open-label study.
A Phase IIa, Randomized, Double-blind, Active-controlled, 12-week Study of Amdoxovir (Two Doses) Versus Tenofovir DF, in Combination With Zidovudine in HIV-1 Treatment-experienced Subjects With M184I/V Mutation in Addition to 0-2 Confirmed Thymidine Analog Mutations.. --- M184I ---
- Has M184I/V mutation in addition to 0-2 thymidine analog mutations (TAMs) at screening. --- M184I ---
A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) are oral, FDA-approved, anti-HIV drugs, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the safety and effectiveness of daily tenofovir 1% gel compared to a vaginal placebo gel, and the safety and effectiveness of oral TDF and oral FTC/TDF compared to an oral placebo in preventing HIV infection among women at risk for sexually transmitted infections.
The primary resistance mutations for the study were pre-defined as K65R and K70E (which confer resistance to TDF), and M184I and M184V (which confer resistance to FTC), for their potential to cause a decrease in susceptibility to the study drug. --- K65R --- --- K70E --- --- M184I ---
K65R, K70E, and M184I were not detected in HIV-1 from any HIV-1 seroconverters while on study product. --- K65R --- --- K70E --- --- M184I ---
Description: Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up.
Measure: Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms Time: For up to 30 months of follow-upDescription: Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).
Measure: Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms Time: For up to 30 months of follow-upDescription: This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).
Measure: Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms Time: For up to 30 months of follow-upDescription: Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up. Note that the data for both of these arms were censored on the date when sites were asked to discontinue treatment in the oral TDF group.
Measure: Person-years of Follow-up of Oral TDF and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).
Measure: Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).
Measure: Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up.
Measure: Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).
Measure: Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).
Measure: Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: This measure describes the number of participants with elevated serum creatinine levels, the only safety outcome of concern where a significant difference was detected between an active arm and the corresponding placebo arm.
Measure: Extended Safety of Daily Tenofovir 1% Gel, Oral TDF, and Oral FTC/TDF in Women at Risk for Sexually Transmitted HIV Infection Based on Occurrence of Grade 2, 3, and 4 Adverse Events Time: Throughout study, up to 2.5 yearsDescription: The primary resistance mutations for the study were pre-defined as K65R and K70E (which confer resistance to TDF), and M184I and M184V (which confer resistance to FTC), for their potential to cause a decrease in susceptibility to the study drug. K65R, K70E, and M184I were not detected in HIV-1 from any HIV-1 seroconverters while on study product. The number of HIV-1 seroconverters while on study with the M184V resistance mutation are reported for this outcome measure.
Measure: Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product Time: Throughout study, up to 2.5 yearsThis 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.
- Subject is virologically suppressed on ATV + RTV + TDF/FTC defined as HIV-1 RNA M184I/V or 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 ---
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 24Description: 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 48This two part study will 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 agent in participants harboring the archived nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance mutation M184V and/or M184I in HIV-1 reverse transcriptase. In Part 1, participants will have M184V and/or M184I (mixtures are acceptable) in reverse transcriptase without any other NRTI resistance mutation. 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. In Part 2, participants will have M184V and/or M184I (mixtures are acceptable) in reverse transcriptase with or without 1 or 2 thymidine analog-associated mutations.
Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) in Virologically-Suppressed HIV-1 Infected Adults Harboring the Archived Isolated NRTI Resistance Mutation M184V/M184I This two part study will 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 agent in participants harboring the archived nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance mutation M184V and/or M184I in HIV-1 reverse transcriptase. --- M184V --- --- M184V --- --- M184I ---
In Part 1, participants will have M184V and/or M184I (mixtures are acceptable) in reverse transcriptase without any other NRTI resistance mutation. --- M184V --- --- M184I ---
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. In Part 2, participants will have M184V and/or M184I (mixtures are acceptable) in reverse transcriptase with or without 1 or 2 thymidine analog-associated mutations. --- M184V --- --- M184I ---
Key Inclusion Criteria: - Documented historical genotype report showing M184V and/or M184I (mixtures are acceptable) in reverse transcriptase. --- M184V --- --- M184I ---
- Proviral DNA test must not have additional exclusion resistance mutations against PIs, NRTIs and INSTIs - Part 1 (first 50 individuals): Historical genotype report must show 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, T69 insertion and Q151M mutation complex [A62V, V75I, F77L, F116Y, Q151M] - Part 2 (after the interim efficacy review - 50 individuals): Historical genotype report must show M184V and/or M184I in reverse transcriptase WITH or WITHOUT one or two thymidine analogue-associated mutations (TAMs) [TAMs are: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E/N/R]. --- M184V --- --- M184I ---
- Proviral DNA test must not have additional exclusion resistance mutations against PIs, NRTIs and INSTIs - Part 1 (first 50 individuals): Historical genotype report must show 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, T69 insertion and Q151M mutation complex [A62V, V75I, F77L, F116Y, Q151M] - Part 2 (after the interim efficacy review - 50 individuals): Historical genotype report must show M184V and/or M184I in reverse transcriptase WITH or WITHOUT one or two thymidine analogue-associated mutations (TAMs) [TAMs are: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E/N/R]. --- M184V --- --- M184I --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215Y --- --- K219Q --- --- K65R --- --- Q151M --- --- A62V --- --- V75I --- --- F77L --- --- F116Y --- --- Q151M --- --- M184V --- --- M184I ---
Description: This outcome measure will be assessed with any post Day 1 sample with HIV-1 RNA ≥ 50 copies/mL.
Measure: Proportion of participants with emergence of new mutations in HIV-1 reverse transcriptase and integrase Time: Up to 48 weeks