Currently, the preferred anti-HIV regimens used in the United States consist of two nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleoside 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 test the safety, tolerability, and effectiveness of 4 different regimens in HIV infected adults who have never taken anti-HIV drugs.

Condition	Intervention	Phase
HIV Infections	Drug: Abacavir/lamivudine  Drug: Atazanavir  Drug: Efavirenz  Drug: Emtricitabine/tenofovir disoproxil fumarate  Drug: Ritonavir	Phase III

Further Study Details: 

Primary Outcomes: Time from randomization to virologic failure (HIV viral load of 1000 copies/ml or greater at or after Week 16 and before Week 24 or 200 copies/ml or greater at or after Week 24); time from treatment dispensation to the first development of a Grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline; time from treatment dispensation to treatment discontinuation
Secondary Outcomes: Time from treatment dispensation to regimen completion (first occurrence of virologic failure or treatment discontinuation); HIV viral load levels less than 50 and less than 200 copies/ml at 48 and 96 weeks; CD4 count and other immunologic responses at 48 and 96 weeks and at virologic failure; HIV-1 drug resistance patterns at baseline and at time of virologic failure; occurrence of fasting hypertriglyceridemia, indication of drug therapy of dyslipidemia, receipt of new drug therapy for dyslipidemia, change from baseline in components of lipid panel at Weeks 8, 24, 48, 72, and 96; virologic and immunologic response, safety, and tolerability by race/ethnicity, age, gender, and hepatitis B and C coinfection; occurrence of targeted clinical events, including death, AIDS-defining illness, and HIV-1 related events (including the CDC Category B diseases)
Expected Total Enrollment:  1800

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 4 different treatment regimens in HIV infected treatment-naive adults.

The treatment portion of this study will last 96 weeks. Participants will be followed for an additional 48 weeks after the treatment portion is completed. Participants will be randomly assigned to one of four arms:

• Arm A participants will receive EFV, FTC/TDF, and placebo for ABC/3TC.
• Arm B participants will receive EFV, placebo for FTC/TDF, and ABC/3TC.
• Arm C participants will receive ritonavir (RTV) boosted ATV, FTC/TDF, and placebo for ABC/3TC.
• Arm D participants will receive RTV boosted ATV, placebo for FTC/TDF, and ABC/3TC.

There will be 16 study visits; they will occur at study entry, Weeks 1, 2, 4, 8, 16, 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.

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• HIV-1 infected. A resistance assay must be obtained if the participant has evidence of recent infection. More information on this criterion can be found in the protocol.
• Antiretroviral naive, defined as 7 days or less of ARV treatment at any time prior to study entry. Participants who have received ARVs as part of post-exposure prophylaxis or who have received a investigational drug that was not an NRTI, NNRTI, or PI are eligible for this study.
• HIV viral load greater than 1000 copies/ml within 90 days of study entry
• Willing to use acceptable forms of contraception
• Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria:

• Immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry
• Known allergy/sensitivity to study drugs or their formulations
• Active alcohol or drug use that, in the opinion of the investigator, may interfere with the study
• Serious illness requiring systemic treatment or hospitalization. Patients who have completed therapy or are clinically stable on therapy for at least 7 days prior to study entry are not excluded.
• Known cardiac conduction system disease
• Requires certain medications
• Any major drug resistance-associated mutation on genotypic resistance testing
• Current imprisonment or involuntary incarceration for psychiatric or physical (e.g., infectious disease) illness
• Pregnancy or breastfeeding

Please refer to this study by ClinicalTrials.gov identifier  NCT00118898

Alabama
      University of Alabama at Birmingham, Birmingham,  Alabama,  35924-2050,  United States

Study chairs or principal investigators

Eric Daar, MD,  Study Chair,  Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute   
Paul Sax, MD,  Study Chair,  Division of Infectious Diseases, Brigham and Women''''s Hospital   

Study ID Numbers:  ACTG A5202; ACTG 5224s
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 11, 2005
ClinicalTrials.gov Identifier:  NCT00118898
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-26