Phase II Study of Vicriviroc versus Efavirenz (both with Zidovudine/Lamivudine) in Treatment-Naive Subjects with HIV-1 Infection

Background. Vicriviroc (VCV) is a CCR5 antagonist with nanomolar activity against human immunodeficiency virus (HIV) replication in vitro and in vivo. We report the results of a phase II dose-finding study of VCV plus dual nucleoside reverse-transcriptase inhibitors (NRTIs) in the treatment-naive HIV-1–infected subjects. Methods. This study was a randomized, double-blind, placebo-controlled trial that began with a 14-day com-parison of 3 dosages of VCVwith placebo in treatment-naive subjects infected with CCR5-usingHIV-1. After 14 days of monotherapy, lamivudine/zidovudine was added to the VCV arms; subjects receiving placebo were treated with efavirenz and lamivudine/zidovudine; the planned treatment duration was 48 weeks. Results. Ninety-two subjects enrolled. After 14 days of once-daily monotherapy, the mean viral loads decreased frombaseline values by 0.07 log10 copies/mL in the placebo arm, 0.93 log10 copies/mL in theVCV25mg arm, 1.18 log10 copies/mL in the VCV 50 mg arm, and 1.34 log10 copies/mL in the VCV 75 mg arm (P .001 for each VCV arm vs. the placebo arm). The combination-therapy portion of the study was stopped because of increased rates of virologic failure in the VCV 25mg/day arm (relative hazard [RH], 21.6; 95 % confidence interval [CI], 2.8–168.9) and the VCV 50 mg/day arm (RH, 11.7; 95 % CI, 1.5–92.9), compared with that in the control arm. Conclusions. VCV administered with dual NRTIs in treatment-naive subjects with HIV-1 infection had in-creased rates of virologic failure, compared with efavirenz plus dual NRTIs. No treatment-limiting toxicity wa