ACTG A5202: EFAVIRENZ OR ATAZANAVIR WITH RITONAVIR IN ARV-NAIVE SUBJECTS (AIDS)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a phase IIIB, randomized, four-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced atazanavir (ATV) to efavirenz (EFV), in combination with either daily emtricitabine (FTC)/tenofovir (TDF) or abacavir (ABC)/lamivudine (3TC) and of partially blinded ABC/3TC compared to FTC/TDF in combination with either RTV-enhanced ATV or EFV as initial therapy for HIV-1 infection. Hypotheses: 1) RTV-enhanced ATV in combination with FTC/TDF is equivalent to EFV in combination with FTC/TDF with respect to antiviral potency. 2) RTV-enhanced ATV in combination with ABC/3TC is equivalent to EFV in combination with ABC/3TC with respect to antiviral potency. 3) EFV in combination with ABC/3TC is equivalent to EFV in combination with FTC/TDF with respect to antiviral potency. 4) RTV-enhanced ATV in combination with ABC/3TC is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to antiviral potency. Primary objectives: 1) To compare virologic efficacy between regimens with virologic failure defined as the time to confirmed plasma HIV-1 RNA level ?1000 copies/mL at or after 16 weeks and before 24 weeks or ?200 copies/mL at or after week 24. 2) To compare the safety between regimens with safety defined as the time to first development of Grade 3 or sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline. 3) To compare the tolerability between regimens with tolerability defined as the time to change in one or more drugs in the initial treatment regimen. The study will last approximately 96 weeks beyond the enrollment of the last subject. 1800 subjects (450 per treatment arm) will be enrolled. Subjects will be HIV-1-infected, antiretroviral (ARV) drug-na¿ve (days of ARV treatment at anytime prior to study entry) men and women ?16 years of age with plasma HIV-1 RNA levels >1000 copies/mL. Subjects will be stratified at screening based on plasma HIV-1 RNA levels <100,000 and ?100,000 copies/mL and intent and eligibility to enroll in the metabolic substudy A5224s. At entry subjects will be randomized to one of the following: ARM A: EFV 600 mg QD + FTC 200 mg/TDF 300 mg QD + ABC/3TC placebo QD ARM B: EFV 600 mg QD + ABC 600 mg/3TC 300 mg QD + FTC/TDF placebo QD ARM C: ATV 300 mg QD with RTV 100 mg QD + FTC 200 mg/TDF 300 mg QD + ABC/3TC placebo QD ARM D: ATV 300 mg QD with RTV 100 mg QD + ABC 600 mg/3TC 300 mg QD + FTC/TDF placebo QD A substudy, A5224, will determine long-term metabolic effects: changes in fat, blood sugar, bone density and renal function. Its primary objectives are as follows: 1) To assess changes within treatment arms in peripheral fat changes (limb fat) after the initiation of an ARV regimen containing ABC/3TC or FTC/TDF (Arms B/D or A/C). 2) To compare the effects of initiation of an ARV regimen containing ABC/3TC with those of a regimen containing FTC/TDF on bone mineral density (BMD), as assessed by lumbar spine and hip DEXA (Arms B/D versus A/C). The hypotheses of the substudy are 1) FTC/TDF and ABC/3TC arms in A5202 will be associated with relatively little loss of limb fat. 2) TDF-containing arms will lead to higher rates of bone loss when compared to the other NRTI arms.