Primary Outcomes

Measure: HIV-1 RNA change from baseline over the first 14 days of study

Time: 14 days

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Secondary Outcomes

Measure: safety and tolerability; pharmacokinetics

Time: 14 days

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Primary Outcomes

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 months

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Description: 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 months

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Secondary Outcomes

Description: 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 months

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Description: 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 months

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Description: 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 months

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Description: 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 months

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Description: 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 months

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Description: 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 months

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Description: 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 months

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Description: 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 months

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Description: 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 months

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Primary Outcomes

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-up

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Description: 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-up

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Description: 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-up

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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. 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-up

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Description: 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-up

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Description: 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-up

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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 Oral TDF-FTC and Oral Placebo Arms

Time: For up to 30 months of follow-up

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Description: 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-up

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Description: 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-up

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Description: 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 years

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Secondary Outcomes

Description: 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 years

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Primary Outcomes

Description: The primary study endpoint was the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 24 of study participation. The per-protocol primary analysis was conducted intention-to-treat, with missing evaluations counted as failures. Achievement of HIV-1 viral load below 50 copies/ml was defined as having HIV-1 RNA <50 copies/ml during the Week 24 analysis window (>18 and <30 weeks post-entry).

Measure: The Antiretroviral Activity of Etravirine 400 mg Given Once Daily, With Fixed-dose Truvada Once Daily, Among Treatment-naïve HIV-1 Infected Adults as Measured by the Percentage of Participants With HIV RNA < 50 Copies/mL at Week 24

Time: 24 weeks

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Secondary Outcomes

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 48 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <50 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 48 weeks

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Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 96 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <50 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 96 weeks

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Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <200 copies/ml at Week 24 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <200 Copies/mL at Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 24 weeks

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Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <200 copies/ml at Week 48 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <200 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 48 weeks

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Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA 200 copies/ml at Week 96 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <200 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 96 weeks

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Description: The per-protocol analysis of change in CD4+ cell count from baseline to Week 24 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% confidence interval (CI).

Measure: Change in CD4+ Cell Count From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

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Description: The per-protocol intention-to-treat analysis of change in CD4+ cell count from baseline to Week 48 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% CI.

Measure: Change in CD4+ Cell Count From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 48 weeks

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Description: The per-protocol intention-to-treat analysis of change in CD4+ cell count from baseline to Week 96 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% CI.

Measure: Change in CD4+ Cell Count From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

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Description: Per-protocol, genotype testing was conducted at confirmation of virologic failure if the confirmatory HIV-1 RNA was above the laboratory-specified threshold of 500 copies/mL. HIV-1 genotype was determined using the TRUGENE® HIV-1 assay (Siemens Healthcare Diagnostics, Tarrytown, NY)

Measure: Resistance Mutations in the Subset of Patients With Confirmed Virologic Failure Who Have HIV RNA >500 Copies/mL and Genotype Resistance Results

Time: 96 weeks

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Description: The safety/tolerability endpoint was defined as the first grade 3 or higher sign, symptom or laboratory abnormality that was at least one grade higher than baseline among participants ever exposed to etravirine (regardless of treatment status), or permanent discontinuation of etravirine due to any toxicity (regardless of grade). Modification of tenofovir/emtricitabine was not a safety/tolerability event. The Kaplan-Meier method was used to estimate the proportion of participants ever exposed to etravirine who remained event-free through Week 96, with a 95% CI using Greenwood's variance estimate and a log-log transformation. Time was handled as continuous (weeks from treatment start to event or censoring).

Measure: Tolerability of Etravirine in HIV-1 Infected Adults Initiating Antiretroviral Therapy

Time: 96 weeks

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Description: The Kaplan-Meier method was used to estimate the proportion of participants ever exposed to etravirine who remained event-free through Week 96, with a 95% CI using Greenwood's variance estimate and a log-log transformation. Time was handled as continuous (weeks from treatment start to event or censoring).

Measure: Probability of Remaining Free of a Safety/Tolerability Event at 96 Weeks

Time: 96 weeks

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Description: Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

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Description: Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

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Description: Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 48 weeks

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Description: Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 48 weeks

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Description: Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5.

Measure: Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

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Description: Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

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Description: Changes from baseline to follow-up in limb fat, trunk fat, total body fat, and lean mass were calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Limb and Trunk Fat Distribution as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

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Description: Changes from baseline to follow-up in limb fat, trunk fat, total body fat, and lean mass were calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Limb and Trunk Fat Distribution as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

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Description: Change from baseline to follow-up in fat mass ratio was calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Fat mass ratio was calculated as the ratio of trunk fat percentage and lower limb fat percentage (% trunk fat mass / % lower limb fat mass). Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Fat Mass Ratio as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

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Description: This secondary outcome measure assessed the ratio of semen:plasma concentration of etravirine in paired semen and plasma samples collected from 14 male participants at Week 4 of treatment with etravirine and fixed dose tenofovir/emtricitabine.

Measure: Pharmacokinetics of Etravirine in Genital Secretions of up to 10 Men and up to 10 Women at Week 4 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 4 weeks

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Description: Change from baseline to follow-up in fat mass ratio was calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Fat mass ratio was calculated as the ratio of trunk fat percentage and lower limb fat percentage (% trunk fat mass / % lower limb fat mass). Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Fat Mass Ratio as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

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Description: Population pharmacokinetics were calculated using sparse sampling. Plasma concentrations of etravirine measured in samples from participants who provided blood samples at multiple study visits, with variation in sampling times relative to dosing of etravirine used to cover the spectrum of the dosing schedule. Model simulations and fitting were performed with NONMEM ® 7.3. (ICON, plc) and model exploration was performed with Berkeley Madonna (Berkeley, CA, USA)

Measure: Population Pharmacokinetics of Etravirine 400 mg Once Daily, in Combination With Fixed-dose Emtricitabine-tenofovir Among Treatment-naïve HIV-1 Infected Adults

Time: At or after 4 weeks

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Description: Population pharmacokinetics were calculated using sparse sampling. Plasma concentrations of etravirine measured in samples from participants who provided blood samples at multiple study visits, with variation in sampling times relative to dosing of etravirine used to cover the spectrum of the dosing schedule. Model simulations and fitting were performed with NONMEM ® 7.3. (ICON, plc) and model exploration was performed with Berkeley Madonna (Berkeley, CA, USA)

Measure: Population Pharmacokinetics of Etravirine 400 mg Once Daily, in Combination With Fixed-dose Emtricitabine-tenofovir Among Treatment-naïve HIV-1 Infected Adults: Etravirine AUC-24 Hours at Steady State

Time: At or after 4 weeks

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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 24

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Secondary 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 24

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Description: 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 48

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Description: 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 24

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Description: 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 48

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Description: 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 24

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Description: 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 48

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Description: 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 24

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Description: 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 48

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Description: 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 24

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Description: 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 48

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Description: 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 24

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Description: 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 24

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Description: 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 48

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Description: 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 48

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Description: 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 24

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Description: 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 48

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Description: 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 48

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Description: 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 24

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Description: 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 48

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Description: 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 24

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Description: 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 48

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Description: 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 24

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Description: 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 48

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Primary Outcomes

Description: Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death

Measure: The Antiretroviral Treatment Failure Rate at 12 Months.

Time: 12 months post ART intiation or until time of death

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Secondary Outcomes

Description: Difference between 12 months and randomisation CD4+ count was calculated and then summarised

Measure: Change in CD4+ Cell Count From Randomisation to 12 Months Post-randomisation

Time: Measured at 12 months post ART initiation

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Measure: Tenofovir Resistance, Defined as Presence of K65R, K70E or Any of the TAMS Mutations

Time: From randomisation until either time of termination or time of death

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Measure: Reported Adverse Events With Severity Grades 3 and 4 Based on the DAIDS Toxicity Grading Tables

Time: From randomisation until either time of termination or time of death

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Description: We will assess whether exposure to tenofovir gel at the time of HIV acquisition alters the subsequent humoral and cellular immune responses following antiretroviral treatment initiation

Measure: Cellular and Humoral Immune Responses

Time: 3 years

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Measure: Genital Viral Shedding (Viral Load on Tear Flow)

Time: 3 years

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Primary Outcomes

Measure: Actual Glomerular Filtration Rate (aGFR) Using Iohexol Plasma Clearance (CLiohexol) at Week 24

Time: Week 24

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Description: GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFR = (140 - age) * (mass in kg) * (0.85 if female) divided by 72 * serum creatinine in mg/dL

Measure: Estimated GFR (eGFR) Calculated by Cockcroft-Gault Formula at Week 24

Time: Week 24

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Description: MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender. eGFR (mL/min/1.73 m^2) = 186 * (Scr)^-1.154 * (Age)^(-0.203) * (0.742 if female) * (1.212 if black). Scr = serum creatinine in mg/dL

Measure: Estimated GFR Calculated by Modification of Diet in Renal Disease (MDRD) Formula at Week 24

Time: Week 24

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Secondary Outcomes

Measure: Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Urine Glucose (by Dipstick)

Time: Up to 24 weeks plus 30 days

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Measure: Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Serum Glucose (Fasting)

Time: Up to 24 weeks plus 30 days

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Measure: Percentage Change From Baseline in Urine Albumin to Creatinine Ratio (mg/g) at Week 24

Time: Baseline; Week 24

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Measure: Percentage Change From Baseline in Urine Protein to Creatinine Ratio (mg/g) at Week 24

Time: Baseline; Week 24

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Measure: Percentage Change From Baseline in Urine β2-microglobulin to Creatinine Ratio (µg/g) at Week 24

Time: Baseline; Week 24

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Measure: Percentage Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio (µg/g) at Week 24

Time: Baseline; Week 24

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Description: Cmax is defined as the maximum observed concentration of drug in plasma.

Measure: Pharmacokinetic (PK) Parameter: Cmax for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: Tmax is defined as the time of Cmax.

Measure: PK Parameter: Tmax for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: Clast is defined as the last observable concentration of drug.

Measure: PK Parameter: Clast for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: Tlast is defined as the time of Clast. Plasma samples for PK analysis were collected out to 10 hours postdose, and the predose concentration was used as a surrogate for the 24 hour concentration for PK parameter generation.

Measure: PK Parameter: Tlast for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: Ctau is defined as the observed drug concentration at the end of the dosing interval.

Measure: PK Parameter: Ctau for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: λz is defined as the terminal elimination rate constant.

Measure: PK Parameter: λz for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).

Measure: PK Parameter: AUCtau for COBI

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Measure: PK Parameter: t1/2 for COBI

Time: Predose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: Cmax for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: Tmax for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: Clast for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: Plasma samples for PK analysis were collected out to 10 hours postdose, and the predose concentration was used as a surrogate for the 24 hour concentration for PK parameter generation.

Measure: PK Parameter: Tlast for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: Ctau for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: AUCtau for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: λz for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: t1/2 for RTV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: Cmax for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: Tmax for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: Clast for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: Plasma samples for PK analysis were collected out to 10 hours postdose, and the predose concentration was used as a surrogate for the 24 hour concentration for PK parameter generation.

Measure: PK Parameter: Tlast for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: Ctau for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: λz for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: AUCtau for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Measure: PK Parameter: t1/2 for TFV

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

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Description: AUC inf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

Measure: PK Parameter: AUCinf for Iohexol

Time: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" on Day 1 and Weeks 4, 8, 16, and 24

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Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL Week 24 as Determined by Snapshot Algorithm

Time: Week 24

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Measure: Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count at Week 24

Time: Baseline; Week 24

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Description: Incidences of adverse events and laboratory abnormalities will be summarized.

Measure: Percentage of Participants Experiencing Adverse Events (AEs)

Time: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days)

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Description: Graded laboratory abnormalities were defined as values that increased at least one toxicity grade from predose at any postdose up to the last dose date of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant.

Measure: Percentage of Participants Experiencing Treatment Emergent (TE) Grade 3 or 4 Laboratory Abnormalities

Time: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days)

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Primary Outcomes

Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24

Time: Week 24

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Secondary Outcomes

Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 12 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12

Time: Week 12

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Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 48

Time: Week 48

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Measure: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline; Week 24

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Measure: Change From Baseline in CD4+ Cell Count at Week 48

Time: Baseline; Week 48

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Primary Outcomes

Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 12 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

Measure: Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 12 as Defined by Pure Virologic Response (PVR)

Time: Week 12

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Secondary Outcomes

Description: Development of new resistance mutations was assessed in participants who developed virologic failure, defined as 2 consecutive HIV-1 RNA result ≥ 50 copies/mL at any point in the study or with HIV-1 RNA ≥ 50 copies/mL at last visit.

Measure: Percentage of Participants With Emergence of New Mutations in HIV-1 Reverse Transcriptase and Integrase

Time: Day 1 up to 48 weeks

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Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 24 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using PVR

Time: Week 24

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Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 48 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using PVR

Time: Week 48

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 71 and 98 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the FDA Snapshot Analysis

Time: Week 12

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 24 window was between Day 141 and 210 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the FDA Snapshot Analysis

Time: Week 24

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 295 and 378 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA Snapshot Analysis

Time: Week 48

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Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 12 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 71 and 98 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 12 Using the FDA Snapshot Analysis

Time: Week 12

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Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 24 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 24 window was between Day 141 and 210 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 24 Using the FDA Snapshot Analysis

Time: Week 24

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Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 48 was also analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 12 window was between Day 295 and 378 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 Using the FDA Snapshot Analysis

Time: Week 48

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the Missing = Failure (M = F) Approach

Time: Week 12

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the M = F Approach

Time: Week 24

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = F Approach

Time: Week 48

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the Missing = Excluded (M = E) Approach

Time: Week 12

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the M = E Approach

Time: Week 24

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach

Time: Week 48

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Measure: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 12

Time: Baseline (Day 1); Week 12

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Measure: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline (Day 1); Week 24

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Measure: Change From Baseline in CD4+ Cell Count at Week 48

Time: Baseline (Day 1); Week 48

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Measure: Change From Baseline in CD4 Percentage (%) at Week 12

Time: Baseline (Day 1); Week 12

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Measure: Change From Baseline in CD4 % at Week 24

Time: Baseline (Day 1); Week 24

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Measure: Change From Baseline in CD4 % at Week 48

Time: Baseline (Day 1); Week 48

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Primary Outcomes

Measure: Percent Change From Baseline to Week 48 in Spine BMD

Time: Baseline; Week 48

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Measure: Percent Change From Baseline to Week 48 in Hip BMD

Time: Baseline; Week 48

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Secondary Outcomes

Measure: Percent Change From Baseline to Week 24 in Spine BMD

Time: Baseline; Week 24

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Measure: Percent Change From Baseline to Week 24 in Hip BMD

Time: Baseline; Week 24

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm

Time: Week 24

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Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm

Time: Week 48

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Measure: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline; Week 24

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Measure: Change in Baseline in CD4+ Cell Count at Week 48

Time: Baseline; Week 48

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Primary Outcomes

Description: Sustained Virologic Response (SVR12) was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.

Measure: Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12)

Time: HCV Posttreatment Week 12

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Secondary Outcomes

Description: SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping LDV/SOF treatment.

Measure: Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4)

Time: HCV Posttreatment Week 4

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Description: The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm

Time: 24 weeks after start of HIV treatment

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Measure: Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment

Time: Up to 32 weeks plus 30 days

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Primary Outcomes

Description: The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) <50 c/mL at Week 48 will be assessed using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks).

Measure: Percentage of patients with HIV-1 RNA levels of less than 50 copies/mL at week 48

Time: 48 weeks

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Secondary Outcomes

Description: The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) <400 c/mL at Week 24 will be assessed using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm.

Measure: Percentage of patients with HIV-1 RNA <400 copies/mL at week 24

Time: 24 weeks

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Description: An genotiping test will be made at time to virological failure to detect mutation across reverse transcriptase (RT), and Protease (PRO). Protocol defined virological failure was defined as confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 or confirmed plasma HIV-1 RNA levels >=50 copies/mL at week 48

Measure: Number and type of resistance mutations in case of virologic failure

Time: from week 24 to week 48

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Description: Change from Baseline in CD4+ cell counts will be assessed at Weeks 24 and 48.

Measure: CD4+ lymphocyte count and change between baseline (defined as the average between screening and baseline visit values) and weeks 24 and 48

Time: week 24 and 48

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Description: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

Measure: Frequency, type and severity of adverse events and laboratory abnormalities.

Time: week 24 and 48

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Description: Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline (BS) to a CDC CAT C event (EV); CDC CAT B at BS to a CDC CAT C EV; CDC CAT C at BS to a new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.

Measure: Clinical disease progression (CDP)

Time: week 24 and 48

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Description: The evaluation of quality of life will be done through two validated instruments: the Medical Outcomes Study HIV Health Survey ( MOS - HIV) and EuroQol 5D (EQ - 5D ) . Both instruments will be administered to patients at baseline , week 24 and week 48 .

Measure: Changes in quality of life

Time: baseline, week 24 and week 48

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Primary Outcomes

Description: Change in total energy expenditure (kcal/day)

Measure: Change in energy balance

Time: 24 weeks

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Primary Outcomes

Description: Number of patients with virologic suppression, defined as HIV RNA <50 copies/ml at week 24 RNA.

Measure: Virologic Suppression Rates

Time: 1 year

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Description: Number of patients retained in study, defined as at least 2 visits or 2 HIV-1 RNA viral load reports occurring at least 3 months apart within the 12-month study time period

Measure: Retention in Care

Time: 1 year

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Secondary Outcomes

Description: Favorable outcomes concerning health and and social related determinants as assessed by responses to a series of Patient Reported Outcomes at 6 and 12 months. See full list in attached documents.

Measure: Patient Reported Outcomes concerning social and health related barriers

Time: 1 year

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