Clinical trial NCT00084136
Conditions: HIV Infections
Keywords: Treatment Naive Adherence Drug Resistance Treatment Failure
Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Start date: 2005-05-01; Completion date: 2010-05-01
Enrollment: 1571 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study compared 3 different three-drug combinations in HIV infected individuals starting their first HIV treatment regimens. Participants were recruited from resource-limited areas in Africa, Asia, South America, Haiti, and also from the United States. The study hypothesis was each of the once daily combinations (PI based, or NNRTI based) would not have inferior efficacy compared to the twice daily NNRTI based combination.

Detailed description:
In developed countries, standard effective antiretroviral (ARV) therapy for treatment-naive HIV infected people includes three-drug combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, direct comparisons of ARV efficacy in persons that more closely reflect the worldwide demographics of HIV-1 infection are needed.\> \> Trial participants were recruited in Africa (Malawi, South Africa, Zimbabwe), Asia (India, Thailand), South America (Brazil, Peru), Haiti, and the United States.\>

\> All participants were randomly assigned to one of three arms, and random allocation was stratified by 2 factors: country, and screening plasma HIV-1 RNA level (\< 100,000 copies/mL versus \>= 100,000 copies/mL). Participants assigned to the ZDV/3TC+EFV arm received lamivudine/zidovudine twice daily and efavirenz once daily. Participants assigned to the ddI+FTC+ATV arm received emtricitabine, atazanavir, and enteric-coated didanosine once daily. Participants assigned to the TDF/FTC+EFV arm received emtricitabine, tenofovir disoproxil fumarate, and efavirenz once daily. \>

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\> Physical exam and blood collection occurred at entry and at most study visits. Participants experiencing virologic failure were offered a switch to another regimen. \>

\> On May 23, 2008, the ddI+FTC+ATV was closed following a planned interim review by the study's independent Data and Safety Monitoring Board (DSMB). The DSMB recommendation was based upon compelling evidence that this arm had significantly more virologic failure (and therefore was inferior when) compared to the ZDV/3TC+EFV arm . Participants still receiving ddI+FTC+ATV were offered alternative medications, and all participants continued to be followed. \>

\> On November 3, 2009, the DSMB recommended that the study close to all follow-up on May 31, 2010, before the designed termination (based on 30% of participants meeting the primary outcome) was met. The board observed that the recent accumulation of primary efficacy events (i.e. regimen failures) was very slow. Therefore, if the study were to continue another 1-2 years, the precision gained for treatment comparisons would likely be small.

Arms: arm 1: ZDV/3TC+EFV participants will receive lamivudine/zidovudine and efavirenz arm 2: ddI+FTC+ATV participants will receive emtricitabine, atazanavir, and enteric-coated didanosine arm 3: TDF/FTC+EFV participants will receive emtricitabine/tenofovir disoproxil fumarate and efavirenz
Interventions: intervention 1: Atazanavir intervention 2: Didanosine (enteric-coated) intervention 3: Efavirenz intervention 4: Emtricitabine intervention 5: Emtricitabine/Tenofovir disoproxil fumarate intervention 6: Lamivudine/Zidovudine
Intervention descriptions: intervention 1: 400 mg taken orally daily intervention 2: 400 mg taken orally daily intervention 3: 600 mg taken orally daily intervention 4: 200 mg taken orally daily intervention 5: 200 mg/300 mg taken orally once daily intervention 6: 150 mg/300 mg taken orally twice daily

Protocol documents: