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

This study has been completed.
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00112047
First received: May 27, 2005
Last updated: October 11, 2010
Last verified: October 2010
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Emtricitabine (FTC)
Drug: Tenofovir Disoproxil Fumarate (TDF)
Drug: Efavirenz (EFV)
Drug: FTC/TDF
Drug: FTC/TDF/EFV
Drug: Lamivudine/zidovudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 48 (Defined by FDA TLOVR Algorithm) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With HIV-1 RNA < 50 c/mL at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 48 [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 48 [ Time Frame: Baseline to 48 Weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 48 [ Time Frame: Baseline to 48 Weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 48 [ Time Frame: Baseline to 48 Weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 48 [ Time Frame: Study baseline to Week 48 ] [ Designated as safety issue: No ]
    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).

  • Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 48 [ Time Frame: Study baseline to Week 48 ] [ Designated as safety issue: No ]
    Change from study baseline to Week 48 in CD4 cell count = Week 48 CD4 cell count value minus study baseline CD4 cell count value

  • Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 96 (Defined by FDA TLOVR Algorithm) [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 96 (Defined by FDA TLOVR Algorithm) [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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.

  • Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 96 [ Time Frame: Study baseline to Week 96 ] [ Designated as safety issue: No ]
    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).

  • Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 96 [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
    Change from study baseline to Week 96 in CD4 cell count = Week 96 CD4 cell count value minus study baseline CD4 cell count value

  • Change in Limb Fat (kg) From Week 48 to Week 96 [ Time Frame: Week 48 to Week 96 ] [ Designated as safety issue: Yes ]
    Change from Week 48 to Week 96 in limb fat = Week 96 limb fat value minus Week 48 limb fat value.

  • Change in Trunk Fat (kg) From Week 48 to Week 96 [ Time Frame: Week 48 to Week 96 ] [ Designated as safety issue: Yes ]
    Change from Week 48 to Week 96 in trunk fat = Week 96 trunk fat value minus Week 48 trunk fat value

  • Change in Total Body Fat (kg) From Week 48 to Week 96 [ Time Frame: 48 weeks to 96 weeks ] [ Designated as safety issue: Yes ]
    Change from Week 48 to Week 96 in total body fat = Week 96 total body fat value minus Week 48 total body fat value

  • Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 144 (Defined by FDA TLOVR Algorithm) [ Time Frame: 144 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 144 (Defined by FDA TLOVR Algorithm) [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 144 [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 144 [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 144 [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 144 [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) at Week 144 [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) at Week 144 [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    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.

  • Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 144 [ Time Frame: Study baseline to Week 144 ] [ Designated as safety issue: No ]
    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).

  • Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 144 [ Time Frame: Baseline to Week 144 ] [ Designated as safety issue: No ]
    Change from study baseline to Week 144 in CD4 cell count = Week 144 CD4 cell count value minus study baseline CD4 cell count value

  • Change in Limb Fat (kg) From Week 48 to Week 144 [ Time Frame: Week 48 to Week 144 ] [ Designated as safety issue: Yes ]
    Change from Week 48 to Week 144 in limb fat = Week 144 limb fat value minus Week 48 limb fat value

  • Change in Trunk Fat (kg) From Week 48 to Week 144 [ Time Frame: Week 48 to Week 144 ] [ Designated as safety issue: Yes ]
    Change from Week 48 to Week 144 in trunk fat = Week 144 trunk fat value minus Week 48 trunk fat value

  • Change in Total Body Fat (kg) From Week 48 to Week 144 [ Time Frame: Week 48 to Week 144 ] [ Designated as safety issue: Yes ]
    Change from Week 48 to Week 144 in total body fat = Week 144 total body fat value minus Week 48 total body fat value

  • Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96) Defined by the FDA TLOVR Algorithm [ Time Frame: Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96) Defined by the FDA TLOVR Algorithm [ Time Frame: Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96) [ Time Frame: Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96) [ Time Frame: Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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).

  • 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) [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ] [ Designated as safety issue: Yes ]
    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.

  • 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) [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) Through Week 240 (Atripla Week 96) [ Time Frame: Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) Through Week 240 (Atripla Week 96) [ Time Frame: Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 240 (Atripla Week 96) [ Time Frame: Study/Atripla baseline to Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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

  • Change in Limb Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ] [ Designated as safety issue: Yes ]
    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

  • Change in Trunk Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ] [ Designated as safety issue: Yes ]
    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

  • Change in Total Body Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ] [ Designated as safety issue: Yes ]
    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

  • 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. [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ] [ Designated as safety issue: No ]
    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").

  • 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. [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ] [ Designated as safety issue: No ]
    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").

  • Treatment Satisfaction Questionnaire (Satisfaction With Tolerability of Current Treatment Regimen) Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline. [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ] [ Designated as safety issue: No ]
    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").

  • Treatment Satisfaction Questionnaire (General Satisfaction With Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline. [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ] [ Designated as safety issue: No ]
    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").

  • 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. [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ] [ Designated as safety issue: No ]
    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").

  • Quality of Life (SF-12v2 Health Survey: Physical Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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).

  • Quality of Life (SF-12v2 Health Survey: Mental Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ] [ Designated as safety issue: No ]
    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).


Enrollment: 517
Study Start Date: July 2003
Study Completion Date: June 2009
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Sustiva
Drug: Lamivudine/zidovudine
Fixed-dose combination tablet containing lamivudine 150 mg/zidovudine 300 mg, taken twice daily, for 240 weeks
Other Name: 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: Emtricitabine (FTC)
Capsule containing 200 mg FTC, taken once daily, for 96 weeks
Other Name: Emtriva
Drug: Tenofovir Disoproxil Fumarate (TDF)
Tablet containing 300 mg TDF, taken once daily, for 96 weeks
Other Name: Viread
Drug: Efavirenz (EFV)
Tablet containing 600 mg EFV, taken once daily, for 96 weeks
Other Name: Sustiva
Drug: FTC/TDF
Fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg, once daily, from Week 96 to 144
Other Name: 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 Name: Atripla (ATR)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112047

Locations
United States, California
AIDS Healthcare Foundation Research
Beverly Hills, California, United States, 90211
United States, District of Columbia
Capital Medical Associates, P.C.
Washington, District of Columbia, United States, 20036
United States, Florida
Orlando Immunology Center
Orlando, Florida, United States, 32804
United States, Illinois
NorthStar Medical Center
Chicago, Illinois, United States, 60657
United States, North Carolina
Jemsek Clinic
Huntersville, North Carolina, United States, 28078
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Andrew Cheng, MD, PhD Gilead Sciences
  More Information

Additional Information:
Publications:
Responsible Party: Steven Chuck MD, Vice President, HIV Therapeutics, Clinical Research, Gilead Sciences, Inc
ClinicalTrials.gov Identifier: NCT00112047     History of Changes
Other Study ID Numbers: GS-01-934
Study First Received: May 27, 2005
Results First Received: June 22, 2010
Last Updated: October 11, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Human Immunodeficiency Virus

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Efavirenz
Emtricitabine
Lamivudine
Lamivudine, zidovudine drug combination
Tenofovir
Tenofovir disoproxil
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014