Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection

Objective:To assess efficacy and safety of cobicistat versus ritonavir as pharmacoenhancers for atazanavir when administered with emtricitabine/tenofovir df as initial treatment for HIV-1 infection. Design:Randomized, partially placebo-controlled, double-blind, multicenter study. Participants:Antiretroviral treatment-naive adults, screening HIV-1 RNA of at least 5000 copies/ml and CD4 cell count more than 50 cells/&mgr;l. Intervention:Randomized 2 : 1 (stratified by HIV RNA ⩽ or >100 000 copies/ml) to receive placebo-blinded once-daily cobicistat 150 mg or ritonavir 100 mg with open-label atazanavir and fixed-dose emtricitabine/tenofovir df. Main outcome measures:Efficacy and safety at weeks 24 and 48. Results:Eighty-four percent of ATV/co participants and 86% of ATV/r participants suppressed HIV-1 RNA (<50 copies/ ml) at week 24, and 82 and 86% at week 48, respectively, and mean CD4 cell count increased 203 and 199 cells/&mgr;l at week 24 and 208 and 177 cells/&mgr;l at week 48, respectively. Study treatment discontinuation due to adverse events occurred in 4% ATV/co and in 3% ATV/r participants through 48 weeks. Treatment-related adverse events occurred in 36% ATV/co and 48% ATV/r participants; hyperbilirubinemia occurred in 96 and 100%, and ocular icterus or jaundice occurred in 14 and 17%, respectively. Mean estimated glomerular filtration rate (Cockcroft–Gault, ml/min) decrease occurred in both treatment groups and was evident at week 2 (ATV/co −9, ATV/r −4), reached a nadir by week 24 (−15, −14, respectively), and did not progress further through week 48 (−13, −14). Conclusion:Using cobicistat and ritonavir as pharmacoenhancers for atazanavir and administered with emtricitabine/tenofovir df achieved comparable rates of virologic suppression and CD4 cell count increase with satisfactory safety profiles.