Tenofovir Disoproxil Fumarate/Emtricitabine/Efavirenz Versus Combivir/Efavirenz in Antiretroviral-Naive HIV-1 Infected Subjects
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Emtricitabine (FTC); Tenofovir Disoproxil Fumarate (TDF); Efavirenz (EFV); FTC/TDF; FTC/TDF/EFV; Lamivudine/zidovudine
Intervention description: Capsule containing 200 mg FTC, taken once daily, for 96 weeks; Tablet containing 300 mg TDF, taken once daily, for 96 weeks; Tablet containing 600 mg EFV, taken once daily, for 96 weeks; Fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg, once daily, from Week 96 to 144; Fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg/EFV 600 mg, taken once daily, from Week 144 to 240; Fixed-dose combination tablet containing lamivudine 150 mg/zidovudine 300 mg, taken twice daily, for 240 weeks
Intervention MeSH terms: Tenofovir; Lamivudine; Emtricitabine; Zidovudine; Efavirenz; Lamivudine, zidovudine drug combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 517.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Human Immunodeficiency Virus

Summary:

      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.
    

Eligibility 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.