Tenofovir Disoproxil Fumarate/Emtricitabine/Efavirenz Versus Combivir/Efavirenz in Antiretroviral-Naive HIV-1 Infected Subjects

A Phase 3, Randomized, Multicenter Study of the Treatment of Antiretroviral-Naive HIV-1 Infected Subjects Comparing Tenofovir Disoproxil Fumarate and Emtricitabine in Combination With Efavirenz vs Combivir (Lamivudine/Zidovudine) and Efavirenz

The purpose of Study GS-01-934 was to assess the efficacy and safety of two simplified antiretroviral treatment (ART) regimens in ART-naive, human immunodeficiency virus, type 1 (HIV-1) infected participants. The primary objective of the study was to assess noninferiority of emtricitabine (FTC) and tenofovir disoproxil fumarate (tenofovir DF; TDF) in combination with efavirenz (EFV) relative to Combivir (CBV) in combination with EFV in the treatment of HIV-1 infected ART-naive participants, determined by the achievement and maintenance of confirmed HIV-1 ribonucleic acid (RNA) < 400 copies/mL (c/mL) through Week 48, as defined by the United States (US) Food and Drug Administration (FDA) time-to-loss-of-virologic-response (TLOVR) algorithm.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Efavirenz (EFV); Drug: Lamivudine/zidovudine; Drug: Emtricitabine (FTC); Drug: Tenofovir Disoproxil Fumarate (TDF); Drug: FTC/TDF; Drug: FTC/TDF/EFV

Detailed Description

This study was originally planned as a 48-week, Phase 3, randomized, open-label, multicenter study comparing EFV+FTC+TDF (administered as the individual component drugs) versus CBV (lamivudine/zidovudine) + EFV to assess the efficacy and safety of both treatments in ART-Naive, HIV-1 infected participants. The regimen of CBV (administered twice daily) + EFV (administered once daily) served as the active control treatment and was compared with the regimen of EFV+FTC+TDF; each component drug in the EFV+FTC+TDF regimen was administered once daily.

Week 48 to Week 96:

The study was extended and continued to evaluate the efficacy and safety of the two regimens up to a total treatment duration of 96 weeks. The regimen of EFV+FTC+TDF continued to be dosed as the component drugs (EFV + FTC + TDF), once daily, without regard to meals. The regimen of CBV+EFV was dosed as 2 pills (CBV, twice daily in the morning without regard to meals) + EFV (once daily, without regard to meals).

Week 96 to Week 144:

A further study extension changed the 3-pill EFV+FTC+TDF regimen to a 2-pill regimen of EFV + Truvada ([TVD]: a fixed-dose combination pill containing FTC/TDF), once daily without regard to meals, and continued to evaluate the efficacy and safety of the two regimens for a further 48 weeks up to a total study treatment duration of 144 weeks. The regimen of CBV+EFV continued to be dosed as 2 pills (CBV, twice daily in the morning without regard to meals) + EFV (once daily, without regard to meals).

Week 144 to end of study (Week 240):

A final study extension provided all study participants from both treatment regimens the option to switch their respective treatments to the 1-pill regimen of for a further 96 weeks up to a total study duration of 240 weeks (5 years) to further assess the efficacy and safety of ART regimen simplification. At sites in France, the study was extended by a further 48 weeks (Year 6) or until ATR became commercially available (whichever happened first); once ATR became commercially available in France participants were not required to complete the full 288 weeks of the study.

• Study Type: Interventional
• Enrollment (Actual): 517
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • AIDS Healthcare Foundation Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, P.C.
  • Florida
    • Orlando, Florida, United States, 32804
      • Orlando Immunology Center
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Jemsek Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Participants must have met all inclusion criteria within 28 days prior to randomization unless specified otherwise including:

• Plasma HIV-1 RNA levels greater than 10,000 c/mL using Roche Amplicor HIV-1 Monitor Test Version 1.5 Standard
• Adequate renal function: Calculated creatinine clearance greater than or equal to 50 mL/min according to the Cockcroft-Gault Formula.
• Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) 3 x upper limit of normal (ULN).
• Total bilirubin less than or equal to 1.5 mg/dL.
• Adequate hematologic function (absolute neutrophil count greater than or equal to 1,000/mm^3; platelets greater than or equal to 50,000/mm^3; hemoglobin greater than or equal to 8.0 g/dL).
• Serum amylase less than or equal to 1.5 x ULN.
• Serum phosphorus greater than or equal to 2.2 mg/dL.
• Willingness to use effective contraception by both males and females while on study treatment and for 30 days following study drug completion.
• Life expectancy greater than or equal to 1 year
• The ability to understand and sign written informed consent form obtained prior to initiation of study procedures.

Exclusion Criteria: Participants were not eligible for entry to the study if any of the following were met:

• Prior treatment with any non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), or protease inhibitor (PI).
• A new AIDS-defining condition diagnosed (exception CD4 criteria) within 30 days of baseline.
• Receiving ongoing therapy with any of the following: nephrotoxic agents, probenecid, systemic chemotherapeutic agents, systemic corticosteroids, interleukin-2, drugs that interact with efavirenz. Administration of any of the above medications must be discontinued at least 30 days prior to baseline visit and for duration of study.
• Pregnant or lactating participants.
• Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. Participants with biopsy-confirmed KS were eligible but must not have received any systemic therapy for KS within 30 days of baseline and not anticipated starting systemic therapy during the study.
• Prior history of renal or bone disease.
• Any other clinical condition prior to therapy that would make the participant unsuitable for the study or unable to comply with the dosing requirements in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EFV+CBV; Participants in this group received EFV 600 mg once daily + Combivir ([CBV]; the fixed dose combination pill containing lamivudine 150 mg + zidovudine 300 mg) taken twice daily from the start of the study until Week 144. At Week 144 all participants who opted to roll over into the additional 96-week study extension received Atripla ([ATR]; the fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg/EFV 600 mg) taken once daily until the end of the study (Week 240). At sites in France, the study was extended by a further 48 weeks (Year 6) or until ATR became commercially available (whichever happened first); once ATR became commercially available in France participants were not required to complete the full 288 weeks of the study.	Drug: Efavirenz (EFV); Tablet containing 600 mg EFV, taken once daily, for 96 weeks; Other Names: Sustiva; Drug: Lamivudine/zidovudine; Fixed-dose combination tablet containing lamivudine 150 mg/zidovudine 300 mg, taken twice daily, for 240 weeks; Other Names: Combivir (CBV)
Experimental: EFV+FTC+TDF; Participants in this arm received 3 component drugs: efaviren (EFV; 600 mg) + emtricitabine (FTC; 200 mg) + tenofovir disoproxil fumarate (tenofovir DF [TDF]; 300 mg) as 3 separate pills once daily from the start of the study. At 96 weeks Truvada ([TVD] the fixed-dose combination pill containing FTC/TDF [200/300 mg] once daily) replaced the 2 component drugs FTC + TDF; participants continued to receive EFV 600 mg once daily. At Week 144 all participants who opted to roll over into the further 96-week study extension received ATR. At sites in France, the study was extended by a further 48 weeks (Year 6) or until ATR became commercially available (whichever happened first); once ATR became commercially available in France participants were not required to complete the full 288 weeks of the study.	Drug: Efavirenz (EFV); Tablet containing 600 mg EFV, taken once daily, for 96 weeks; Other Names: Sustiva; Drug: Emtricitabine (FTC); Capsule containing 200 mg FTC, taken once daily, for 96 weeks; Other Names: Emtriva; Drug: Tenofovir Disoproxil Fumarate (TDF); Tablet containing 300 mg TDF, taken once daily, for 96 weeks; Other Names: Viread; Drug: FTC/TDF; Fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg, once daily, from Week 96 to 144; Other Names: Truvada (TVD); Drug: FTC/TDF/EFV; Fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg/EFV 600 mg, taken once daily, from Week 144 to 240; Other Names: Atripla (ATR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 48 (Defined by the Food and Drug Administration [FDA] Time-to-Loss-of Virologic Response [TLOVR] Algorithm	Participants who achieved/maintained confirmed HIV-1 RNA < 400 c/mL had to satisfy the following criteria: 1) not experienced death, permanent study drug discontinuation, or addition of new antiretroviral drug except nevirapine in place of EFV prior to Week 48 visit; 2) achieved confirmed HIV-1 RNA < 400 c/mL on 2 consecutive visits prior to Week 48 visit (ie, the first of the 2 consecutive HIV-1 RNA < 400 c/mL occurred prior to the Week 48 visit; 3) not had confirmed HIV-1 RNA > 400 c/mL after achievement of confirmed HIV RNA levels < 400 c/mL prior to Week 48 visit.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 48 (Defined by FDA TLOVR Algorithm)	Participants who achieved/maintained confirmed HIV-1 RNA < 50 c/mL had to satisfy the following criteria: 1) not experienced death, permanent study drug discontinuation, or addition of new antiretroviral drug except nevirapine in place of EFV prior to Week 48 visit; 2) achieved confirmed HIV-1 RNA < 50 c/mL on 2 consecutive visits prior to Week 48 visit (that is, the first of the 2 consecutive HIV-1 RNA < 50 c/mL occurred prior to the Week 48 visit; 3) not had confirmed HIV-1 RNA > 50 c/mL after achievement of confirmed HIV RNA levels < 50 c/mL prior to Week 48 visit.	Week 48
Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 48.	The percentage of participants with plasma HIV-1 RNA < 400 c/mL at Week 48. Participants with missing observations/changes in ART were considered to have HIV-1 RNA ≥ 400 c/mL (i.e., ITT missing or switch=failure analysis).	48 weeks
Percentage of Participants With HIV-1 RNA < 50 c/mL at Week 48	The percentage of participants with plasma HIV-1 RNA < 50 c/mL at Week 48. Participants with missing observations/changes in ART were considered to have HIV-1 RNA ≥ 50 c/mL (i.e., ITT missing or switch=failure analysis).	48 Weeks
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 48	TLOVR for participants who achieved a confirmed virologic response was the time to the earliest of: premature study regimen discontinuation or the first of 2 consecutive HIV-1 RNA ≥ 400 c/mL or last HIV-1 RNA ≥ 400 c/mL followed by loss to follow-up. If the time to HIV-1 RNA ≥ 400 c/mL was immediately preceded by missing scheduled visits then the time of virologic failure was replaced by the first such missing visit. Participants who had not achieved a confirmed virologic response before regimen discontinuation were considered "non-responders" on Study Day 1.	Baseline to 48 weeks
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 48	TLOVR for participants who achieved a confirmed virologic response was the time to the earliest of: premature study regimen discontinuation or the first of 2 consecutive HIV-1 RNA ≥ 50 c/mL or last HIV-1 RNA ≥ 50 c/mL followed by loss to follow-up. If the time to HIV-1 RNA ≥ 50 c/mL was immediately preceded by missing scheduled visits then the time of virologic failure was replaced by the first such missing visit. Participants who had not achieved a confirmed virologic response before regimen discontinuation were considered "non-responders" on Study Day 1.	Baseline to 48 Weeks
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 48	Participants who achieved confirmed HIV-1 RNA < 400 c/mL but had not experienced a confirmed relapse were considered censored at the last HIV-1 RNA collection date.	Baseline to 48 Weeks
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 48	Participants who achieved confirmed HIV-1 RNA < 50 c/mL but had not experienced a confirmed relapse were considered censored at the last HIV-1 RNA collection date.	Baseline to 48 Weeks
Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 48	Change from study baseline to Week 48 in HIV-1 RNA in log10 scale (Week 48 HIV-1 RNA value in log10 scale minus study baseline HIV-1 RNA value in log10 scale).	Study baseline to Week 48
Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 48	Change from study baseline to Week 48 in CD4 cell count = Week 48 CD4 cell count value minus study baseline CD4 cell count value	Study baseline to Week 48
Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 96 (Defined by FDA TLOVR Algorithm)	Participants who achieved/maintained confirmed HIV-1 RNA < 400 c/mL had to satisfy the following criteria: 1) not experienced death, permanent study drug discontinuation, or addition of new antiretroviral drug except nevirapine in place of EFV prior to Week 96 visit; 2) achieved confirmed HIV-1 RNA < 400 c/mL on 2 consecutive visits prior to Week 96 visit (that is, the first of the 2 consecutive HIV-1 RNA < 400 c/mL occurred prior to the Week 96 visit; 3) not had confirmed HIV-1 RNA > 400 c/mL after achievement of confirmed HIV RNA levels < 400 c/mL prior to Week 96 visit.	96 Weeks
Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 96 (Defined by FDA TLOVR Algorithm)	Participants who achieved/maintained confirmed HIV-1 RNA < 50 c/mL had to satisfy the following criteria: 1) not experienced death, permanent study drug discontinuation, or addition of new antiretroviral drug except nevirapine in place of EFV prior to Week 96 visit; 2) achieved confirmed HIV-1 RNA < 50 c/mL on 2 consecutive visits prior to Week 96 visit (that is, the first of the 2 consecutive HIV-1 RNA < 50 c/mL occurred prior to the Week 96 visit; 3) not had confirmed HIV-1 RNA > 50 c/mL after achievement of confirmed HIV RNA levels < 50 c/mL prior to Week 96 visit.	Week 96
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 96	TLOVR for participants with confirmed virologic response (2 consecutive HIV-1 RNA < 400 c/mL) prior to study drug discontinuation, was the time to the earliest of premature study regimen discontinuation, or confirmed HIV-1 RNA > 400 c/mL (2 consecutive HIV-1 RNA ≥ 400 c/mL, or the last HIV-1 RNA ≥ 400 c/mL followed by premature study regimen discontinuation due to loss to follow-up). Participants who did not achieve confirmed virologic response before premature study regimen discontinuation or last HIV-1 RNA, were assumed to have lost virologic response on Study Day 1.	Week 96
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 96	TLOVR for participants who achieved a confirmed virologic response was the time to the earliest of: premature study regimen discontinuation or the first of 2 consecutive HIV-1 RNA ≥ 50 c/mL or last HIV-1 RNA ≥ 50 c/mL followed by loss to follow-up. If the time to HIV-1 RNA ≥ 50 c/mL was immediately preceded by missing scheduled visits then the time of virologic failure was replaced by the first such missing visit. Participants who had not achieved a confirmed virologic response before regimen discontinuation were considered "non-responders" on Study Day 1.	Week 96
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 96	Participants who achieved confirmed HIV-1 RNA < 400 c/mL but had not experienced a confirmed relapse were considered censored at the last HIV-1 RNA collection date.	Week 96
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 96	Participants who achieved confirmed HIV-1 RNA < 50 c/mL but had not experienced a confirmed relapse were considered censored at the last HIV-1 RNA collection date.	Week 96
Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 96	Change from study baseline to Week 96 in HIV-1 RNA in log10 scale (Week 96 HIV-1 RNA value in log10 scale minus study baseline HIV-1 RNA value in log10 scale).	Study baseline to Week 96
Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 96	Change from study baseline to Week 96 in CD4 cell count = Week 96 CD4 cell count value minus study baseline CD4 cell count value	Baseline to Week 96
Change in Limb Fat (kg) From Week 48 to Week 96	Change from Week 48 to Week 96 in limb fat = Week 96 limb fat value minus Week 48 limb fat value.	Week 48 to Week 96
Change in Trunk Fat (kg) From Week 48 to Week 96	Change from Week 48 to Week 96 in trunk fat = Week 96 trunk fat value minus Week 48 trunk fat value	Week 48 to Week 96
Change in Total Body Fat (kg) From Week 48 to Week 96	Change from Week 48 to Week 96 in total body fat = Week 96 total body fat value minus Week 48 total body fat value	48 weeks to 96 weeks
Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 144 (Defined by FDA TLOVR Algorithm)	Participants who achieved/maintained confirmed HIV-1 RNA < 400 c/mL had to satisfy the following: 1) not experienced death, permanent study drug discontinuation, or addition of new antiretroviral drug, except nevirapine in place of EFV, prior to Week 144 visit; 2) achieved confirmed HIV-1 RNA < 400 c/mL on 2 consecutive visits prior to Week 144 visit (i.e., the first of the 2 consecutive HIV-1 RNA < 400 c/mL occurred prior to the Week 144 visit; 3) not had confirmed HIV-1 RNA > 400 c/mL after achievement of confirmed HIV-1 RNA levels < 400 c/mL prior to Week 144 visit.	144 weeks
Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 144 (Defined by FDA TLOVR Algorithm)	Participants who achieved/maintained confirmed HIV-1 RNA < 50 c/mL (c/mL) had to satisfy the following criteria: 1) not experienced death, permanent study drug discontinuation, or addition of new antiretroviral drug, except nevirapine in place of EFV, prior to Week 144 visit; 2) achieved confirmed HIV-1 RNA < 50 c/mL on 2 consecutive visits prior to Week 144 visit (that is, the first of the 2 consecutive HIV-1 RNA < 50 c/mL occurred prior to the Week 144 visit; 3) not had confirmed HIV-1 RNA > 50 c/mL after achievement of confirmed HIV-1 RNA levels < 50 c/mL prior to Week 144 visit.	Week 144
Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 144	The percentage of participants with plasma HIV-1 RNA < 400 c/mL at Week 144. Participants with missing observations/changes in ART were considered to have HIV-1 RNA ≥ 400 c/mL (i.e., ITT missing or switch=failure analysis).	Week 144
Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 144	The percentage of participants with plasma HIV-1 RNA < 50 c/mL at Week 144. Participants with missing observations/changes in ART were considered to have HIV-1 RNA ≥ 50 c/mL (i.e., ITT missing or switch=failure analysis).	Week 144
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 144	TLOVR for participants who achieved a confirmed virologic response was the time to the earliest of: premature study regimen discontinuation or the first of 2 consecutive HIV-1 RNA ≥ 400 c/mL or last HIV-1 RNA ≥ 400 c/mL followed by loss to follow-up. If the time to HIV-1 RNA ≥ 400 c/mL was immediately preceded by missing scheduled visits then the time of virologic failure was replaced by the first such missing visit. Participants who had not achieved a confirmed virologic response before regimen discontinuation were considered "non-responders" on Study Day 1.	Week 144
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 144	TLOVR for participants who achieved a confirmed virologic response was the time to the earliest of: premature study regimen discontinuation or the first of 2 consecutive HIV-1 RNA ≥ 50 c/mL or last HIV-1 RNA ≥ 50 c/mL followed by loss to follow-up. If the time to HIV-1 RNA ≥ 50 c/mL was immediately preceded by missing scheduled visits then the time of virologic failure was replaced by the first such missing visit. Participants who had not achieved a confirmed virologic response before regimen discontinuation were considered "non-responders" on Study Day 1.	Week 144
Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) at Week 144	Participants who achieved confirmed HIV-1 RNA < 400 c/mL but had not experienced a confirmed relapse were considered censored at the last HIV-1 RNA collection date.	Week 144
Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) at Week 144	Participants who achieved confirmed HIV-1 RNA < 50 c/mL but had not experienced a confirmed relapse were considered censored at the last HIV-1 RNA collection date.	Week 144
Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 144	Change from study baseline to Week 144 in HIV-1 RNA in log10 scale (Week 144 HIV-1 RNA value in log10 scale minus study baseline HIV-1 RNA value in log10 scale).	Study baseline to Week 144
Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 144	Change from study baseline to Week 144 in CD4 cell count = Week 144 CD4 cell count value minus study baseline CD4 cell count value	Baseline to Week 144
Change in Limb Fat (kg) From Week 48 to Week 144	Change from Week 48 to Week 144 in limb fat = Week 144 limb fat value minus Week 48 limb fat value	Week 48 to Week 144
Change in Trunk Fat (kg) From Week 48 to Week 144	Change from Week 48 to Week 144 in trunk fat = Week 144 trunk fat value minus Week 48 trunk fat value	Week 48 to Week 144
Change in Total Body Fat (kg) From Week 48 to Week 144	Change from Week 48 to Week 144 in total body fat = Week 144 total body fat value minus Week 48 total body fat value	Week 48 to Week 144
Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96) Defined by the FDA TLOVR Algorithm	Participants who achieved/maintained confirmed HIV-1 RNA < 400 c/mL had to satisfy the following criteria: 1) not experienced death, permanent study drug discontinuation, or addition of new antiretroviral drug except nevirapine in place of EFV prior to Week 240 visit; 2) achieved confirmed HIV-1 RNA < 400 c/mL on 2 consecutive visits prior to Week 240 visit (that is, the first of the 2 consecutive HIV-1 RNA < 400 c/mL occurred prior to the Week 240 visit; 3) not had confirmed HIV-1 RNA > 400 c/mL after achievement of confirmed HIV RNA levels < 400 c/mL prior to Week 240 visit.	Week 144 (Atripla baseline) to Week 240 (Atripla Week 96)
Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96) Defined by the FDA TLOVR Algorithm	Participants who achieved/maintained confirmed HIV-1 RNA < 50 c/mL had to satisfy the following criteria: 1) not experienced death, permanent study drug discontinuation, or addition of new antiretroviral drug except nevirapine in place of EFV prior to Week 240 visit; 2) achieved confirmed HIV-1 RNA < 50 c/mL on 2 consecutive visits prior to Week 240 visit (that is, the first of the 2 consecutive HIV-1 RNA < 50 c/mL occurred prior to the Week 240 visit; 3) not had confirmed HIV-1 RNA > 50 c/mL after achievement of confirmed HIV RNA levels < 50 c/mL prior to Week 240 visit.	Week 144 (Atripla baseline) to Week 240 (Atripla Week 96)
Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96)	The percentage of participants with plasma HIV-1 RNA < 400 c/mL at Week 240. Participants with missing observations/changes in ART were considered to have HIV-1 RNA ≥ 400 c/mL (i.e., ITT missing or switch=failure analysis).	Week 240 (Atripla Week 96)
Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96)	The percentage of participants with plasma HIV-1 RNA < 50 c/mL at Week 240. Participants with missing observations/changes in ART were considered to have HIV-1 RNA ≥ 50 c/mL (i.e., ITT missing or switch=failure analysis).	Week 240 (Atripla Week 96)
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) From Week 144 (Atripla Baseline) Through Week 240 (Atripla Week 96)	TLOVR for participants who achieved a confirmed virologic response was the time to the earliest of: premature study regimen discontinuation or the first of 2 consecutive HIV-1 RNA ≥ 400 c/mL or last HIV-1 RNA ≥ 400 c/mL followed by loss to follow-up. If the time to HIV-1 RNA ≥ 400 c/mL was immediately preceded by missing scheduled visits then the time of virologic failure was replaced by the first such missing visit. Participants who had not achieved a confirmed virologic response before regimen discontinuation were considered "non-responders" on Study Day 1.	Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) From Week 144 (Atripla Baseline) Through Week 240 (Atripla Week 96)	TLOVR for participants who achieved a confirmed virologic response was the time to the earliest of: premature study regimen discontinuation or the first of 2 consecutive HIV-1 RNA ≥ 50 c/mL or last HIV-1 RNA ≥ 50 c/mL followed by loss to follow-up. If the time to HIV-1 RNA ≥ 50 c/mL was immediately preceded by missing scheduled visits then the time of virologic failure was replaced by the first such missing visit. Participants who had not achieved a confirmed virologic response before regimen discontinuation were considered "non-responders" on Study Day 1.	Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)
Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) Through Week 240 (Atripla Week 96)	Participants who achieved confirmed HIV-1 RNA < 400 c/mL but had not experienced a confirmed relapse were considered censored at the last HIV-1 RNA collection date.	Week 240 (Atripla Week 96)
Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) Through Week 240 (Atripla Week 96)	Participants who achieved confirmed HIV-1 RNA < 50 c/mL but had not experienced a confirmed relapse were considered censored at the last HIV-1 RNA collection date.	Week 240 (Atripla Week 96)
Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 240 (Atripla Week 96)	Change from baseline to Week 240 (Atripla Week 96) in CD4 cell count = Week 240 (Atripla Week 96) CD4 cell count value minus baseline CD4 cell count value	Study/Atripla baseline to Week 240 (Atripla Week 96)
Change in Limb Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)	Change from Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) in limb fat = Week 240 (Atripla Week 96) limb fat value minus Week 144 (Atripla Baseline) limb fat value	Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)
Change in Trunk Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)	Change from Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) in trunk fat = Week 240 (Atripla Week 96) trunk fat value minus Week 144 (Atripla Baseline) trunk fat value	Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)
Change in Total Body Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)	Change from Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) in total body fat = Week 240 (Atripla Week 96) total body fat value minus Week 144 (Atripla Baseline) total body fat value	Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)
Treatment Satisfaction Questionnaire (Satisfaction With Convenience and Simplicity of Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.	Participants were asked: "In general, how satisfied are you with the convenience and simplicity of your current treatment regimen?" Possible responses were on a 4-category scale: "very satisfied"; "somewhat satisfied"; "somewhat dissatisfied"; and "very dissatisfied". For the evaluation of changes in treatment satisfaction from Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) responses were dichotomized into "very satisfied" and "not very satisfied" ("not very satisfied" included "very dissatisfied"; "somewhat dissatisfied"; and "somewhat satisfied").	Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96)
Treatment Satisfaction Questionnaire (Satisfaction With Current Treatment Regimen to Control HIV): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.	Participants were asked: "In general, how satisfied are you with the ability of your current treatment regimen to control your HIV infection?" Possible responses were on a 4-category scale: "very satisfied"; "somewhat satisfied"; "somewhat dissatisfied"; and "very dissatisfied". For the evaluation of changes in treatment satisfaction from Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) responses were dichotomized into "very satisfied" and "not very satisfied" ("not very satisfied" included "very dissatisfied"; "somewhat dissatisfied"; and "somewhat satisfied").	Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96)
Treatment Satisfaction Questionnaire (Satisfaction With Tolerability of Current Treatment Regimen) Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.	Participants were asked: "In general, how satisfied are you with your ability to tolerate your current treatment regimen?" Possible responses were on a 4-category scale: "very satisfied"; "somewhat satisfied"; "somewhat dissatisfied"; and "very dissatisfied". For the evaluation of changes in treatment satisfaction from Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) responses were dichotomized into "very satisfied" and "not very satisfied" ("not very satisfied" included "very dissatisfied"; "somewhat dissatisfied"; and "somewhat satisfied").	Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96)
Treatment Satisfaction Questionnaire (General Satisfaction With Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.	Participants were asked: "In general, how satisfied are you with your current treatment regimen?" Possible responses were on a 4-category scale: "very satisfied"; "somewhat satisfied"; "somewhat dissatisfied"; and "very dissatisfied". For the evaluation of changes in treatment satisfaction from Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) responses were dichotomized into "very satisfied" and "not very satisfied" ("not very satisfied" included "very dissatisfied"; "somewhat dissatisfied"; and "somewhat satisfied").	Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96)
Treatment Satisfaction Questionnaire (Bothered With the Side Effects of Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.	Participants were asked: "How bothered are you with the side effects of your current treatment regimen?" Possible responses were on a 4-category scale: "does not bother me"; "bothers me a little bit"; "bothers me a lot"; and "bothers me terribly". For the evaluation of the change in treatment satisfaction from Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) responses were dichotomized into "does not bother me" and "bothers me" ("bothers me" included "bothers me a little bit"; "bothers me a lot"; "bothers me terribly").	Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96)
Quality of Life (SF-12v2 Health Survey: Physical Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)	The change from Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) in the SF-12v2 Health Survey: Physical Component Summary (PCS). The SF-12v2 includes 8 concepts commonly represented in health surveys: physical functioning, role functioning physical, bodily pain, general health, vitality, social functioning, role functioning emotional, and mental health. Results are expressed in terms of 2 composite scores: the PCS and the Mental Component Summary (MCS). PCS and MCS values can range from 0 to 100 and are designed to have a mean value of 50 and SD of 10 (in the general population).	Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)
Quality of Life (SF-12v2 Health Survey: Mental Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)	The change from Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) in the SF-12v2 Health Survey MCS. The SF-12v2 includes 8 concepts commonly represented in health surveys: physical functioning, role functioning physical, bodily pain, general health, vitality, social functioning, role functioning emotional, and mental health. Results are expressed in terms of 2 composite scores: the PCS and the MCS. PCS and MCS values can range from 0 to 100 and are designed to have a mean value of 50 and a SD of 10 (in the general population).	Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Andrew Cheng, MD, PhD, Gilead Sciences

Publications and helpful links

General Publications

• Gallant JE, DeJesus E, Arribas JR, Pozniak AL, Gazzard B, Campo RE, Lu B, McColl D, Chuck S, Enejosa J, Toole JJ, Cheng AK; Study 934 Group. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006 Jan 19;354(3):251-60. doi: 10.1056/NEJMoa051871.

Helpful Links

• Gilead Website
• Viread website
• Sustiva website

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): February 1, 2005
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: May 27, 2005
• First Submitted That Met QC Criteria: May 27, 2005
• First Posted (Estimate): May 30, 2005

Study Record Updates

• Last Update Posted (Estimate): October 13, 2010
• Last Update Submitted That Met QC Criteria: October 11, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: Human Immunodeficiency Virus
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Emtricitabine; Lamivudine; Zidovudine; Efavirenz; Lamivudine, zidovudine drug combination
• Other Study ID Numbers: GS-01-934