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
1 other identifier
interventional
517
1 country
5
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 hiv-infections
Started Jul 2003
Longer than P75 for phase_3 hiv-infections
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2005
CompletedFirst Submitted
Initial submission to the registry
May 27, 2005
CompletedFirst Posted
Study publicly available on registry
May 30, 2005
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2009
CompletedResults Posted
Study results publicly available
October 13, 2010
CompletedOctober 13, 2010
October 1, 2010
1.6 years
May 27, 2005
June 22, 2010
October 11, 2010
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (52)
Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 48 (Defined by FDA TLOVR Algorithm)
Week 48
Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 48.
48 weeks
Percentage of Participants With HIV-1 RNA < 50 c/mL at Week 48
48 Weeks
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 48
Baseline to 48 weeks
Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 48
Baseline to 48 Weeks
- +47 more secondary outcomes
Study Arms (2)
EFV+CBV
ACTIVE COMPARATORParticipants 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.
EFV+FTC+TDF
EXPERIMENTALParticipants 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.
Interventions
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
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (5)
AIDS Healthcare Foundation Research
Beverly Hills, California, 90211, United States
Capital Medical Associates, P.C.
Washington D.C., District of Columbia, 20036, United States
Orlando Immunology Center
Orlando, Florida, 32804, United States
NorthStar Medical Center
Chicago, Illinois, 60657, United States
Jemsek Clinic
Huntersville, North Carolina, 28078, United States
Related Publications (1)
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.
PMID: 16421366RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dara Wambach MA, Associate Director, Regulatory Affairs
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Andrew Cheng, MD, PhD
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
Study Record Dates
First Submitted
May 27, 2005
First Posted
May 30, 2005
Study Start
July 1, 2003
Primary Completion
February 1, 2005
Study Completion
June 1, 2009
Last Updated
October 13, 2010
Results First Posted
October 13, 2010
Record last verified: 2010-10