Clinical trial NCT00118898
Conditions: HIV Infections
Keywords: Treatment Naive
Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Start date: 2005-09-01; Completion date: 2009-11-01
Enrollment: 1864 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Currently, the preferred anti-HIV regimens used in the United States consist of two nucleoside reverse transcriptase inhibitors (NRTIs) and the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV). However, with new anti-HIV drugs being approved, alternative regimens need to be tested to determine if new drug combinations have increased effectiveness in treating HIV. The purpose of this study is to test the safety, tolerability, and effectiveness of four different regimens in HIV-infected adults who have never taken anti-HIV drugs.

Detailed description:
Antiretroviral (ARV) treatment regimens consisting of EFV and two NRTIs are the most commonly prescribed regimens for the initial therapy of HIV-infected people in the United States. Such regimens are popular because the drugs are easy to administer, have overall excellent efficacy, and are well tolerated. However, because of concerns about long-term drug toxicity, the development of drug resistance, and potential complications in pregnant women, it is imperative that other drug combinations be investigated as possible alternative initial regimens. Drugs recently approved by the Food and Drug Administration (FDA) for HIV treatment include the protease inhibitor (PI) atazanavir (ATV) and the two NRTI coformulations emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and abacavir/lamivudine (ABC/3TC). Data are limited on the efficacy of these new drugs when part of anti-HIV drug regimens. This study will evaluate and compare the safety, tolerability, and efficacy of four different treatment regimens in HIV-infected treatment-naive adults.

The treatment portion of this study will last 96 weeks after the last participant is enrolled. Participants will be randomly assigned to one of four arms:

* Arm 1 participants will receive EFV, FTC/TDF, and placebo for ABC/3TC.
* Arm 2 participants will receive EFV, ABC/3TC, and placebo for FTC/TDF.
* Arm 3 participants will receive ritonavir (RTV)-boosted ATV, FTC/TDF, and placebo for ABC/3TC.
* Arm 4 participants will receive RTV-boosted ATV, ABC/3TC and placebo for FTC/TDF.

NOTE: Lopinavir/ritonavir may be used in substitution of other drugs for certain participants.

Study visits will occur at study entry; Weeks 1, 2, 4, 8, 16, and 24; and every 12 weeks thereafter. A physical exam, blood collection, and urine collection will occur at most visits. Two pharmacokinetic blood samples will be collected from participants between Weeks 4 and 24. Participants will undergo adherence training at study entry and will be asked to complete adherence questionnaires at selected study visits. Some participants will be asked to participate in ACTG A5224s, a metabolic substudy of ACTG A5202.

The Data Safety Monitoring Board (DSMB) for A5202 met in January 2008 to review the study. After reviewing the study information, the DSMB noted that certain study regimens were significantly less effective than others. Specifically, ABC/3TC-containing regimens were not as effective in controlling the virus as TDF/FTC-containing regimens for participants entering the study with high viral loads. The DSMB also commented that participants assigned to ABC/3TC had a shorter time until they experienced side effects than participants assigned to TDF/FTC. The DSMB had no safety concerns for the other drug comparisons.

Based on DSMB review, in Feb 2008 participants who started the study with high viral loads were told whether they were taking ABC/3TC or TDF/FTC and offered the option to continue or change their NRTI study drug component, after discussion with their doctor. For participants who started the study with lower screening viral loads, study treatment continued without change.

For 74 participant the reason for first treatment modification was "unblinded and switched" as a consequence of the DSMB results (33 on EFV, ABC/3TC, and placebo FTC/TDF arm; 1 on RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC arm; and 40 on RTV-boosted ATV, ABC/3TC, and placebo FTC/TDF arm).

Arms: arm 1: Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks arm 2: Participants will receive EFV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks arm 3: Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks arm 4: Participants will receive RTV-boosted ATV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
Interventions: intervention 1: Abacavir/Lamivudine intervention 2: Atazanavir intervention 3: Efavirenz intervention 4: Emtricitabine/Tenofovir disoproxil fumarate intervention 5: Ritonavir intervention 6: Abacavir/Lamivudine placebo intervention 7: Emtricitabine/Tenofovir disoproxil fumarate placebo
Intervention descriptions: intervention 1: 600 mg abacavir/300 mg lamivudine tablet taken orally daily intervention 2: 300 mg tablet taken orally daily intervention 3: 600 mg tablet taken orally daily intervention 4: 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily intervention 5: 100 mg tablet taken orally daily intervention 6: Placebo tablet taken orally daily intervention 7: Placebo tablet taken orally daily

Protocol documents: