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

NCT ID: NCT00112047

Last Updated: 2010-10-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

517 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-07-31

Study Completion Date

2009-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Efavirenz (EFV)

Intervention Type DRUG

Tablet containing 600 mg EFV, taken once daily, for 96 weeks

Lamivudine/zidovudine

Intervention Type DRUG

Fixed-dose combination tablet containing lamivudine 150 mg/zidovudine 300 mg, taken twice daily, for 240 weeks

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.

Group Type EXPERIMENTAL

Emtricitabine (FTC)

Intervention Type DRUG

Capsule containing 200 mg FTC, taken once daily, for 96 weeks

Tenofovir Disoproxil Fumarate (TDF)

Intervention Type DRUG

Tablet containing 300 mg TDF, taken once daily, for 96 weeks

Efavirenz (EFV)

Intervention Type DRUG

Tablet containing 600 mg EFV, taken once daily, for 96 weeks

FTC/TDF

Intervention Type DRUG

Fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg, once daily, from Week 96 to 144

FTC/TDF/EFV

Intervention Type DRUG

Fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg/EFV 600 mg, taken once daily, from Week 144 to 240

Interventions

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Emtricitabine (FTC)

Capsule containing 200 mg FTC, taken once daily, for 96 weeks

Intervention Type DRUG

Tenofovir Disoproxil Fumarate (TDF)

Tablet containing 300 mg TDF, taken once daily, for 96 weeks

Intervention Type DRUG

Efavirenz (EFV)

Tablet containing 600 mg EFV, taken once daily, for 96 weeks

Intervention Type DRUG

FTC/TDF

Fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg, once daily, from Week 96 to 144

Intervention Type 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

Intervention Type DRUG

Lamivudine/zidovudine

Fixed-dose combination tablet containing lamivudine 150 mg/zidovudine 300 mg, taken twice daily, for 240 weeks

Intervention Type DRUG

Other Intervention Names

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Emtriva Viread Sustiva Truvada (TVD) Atripla (ATR) Combivir (CBV)

Eligibility Criteria

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Inclusion Criteria

* 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

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Gilead Sciences, Inc

Principal Investigators

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Andrew Cheng, MD, PhD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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AIDS Healthcare Foundation Research

Beverly Hills, California, United States

Site Status

Capital Medical Associates, P.C.

Washington D.C., District of Columbia, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

NorthStar Medical Center

Chicago, Illinois, United States

Site Status

Jemsek Clinic

Huntersville, North Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 16421366 (View on PubMed)

Related Links

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Other Identifiers

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GS-01-934

Identifier Type: -

Identifier Source: org_study_id