Vicriviroc in combination therapy with an optimized regimen for treatment-experienced subjects: 48-Week results of the VICTOR-El phase 2 trial

Background. Agents that block the CCR5 coreceptor for human immunodeficiency virus (HIV) have demonstrated potent antiretroviral activity. In early clinical studies, the CCR5 antagonist vicriviroc proved to be a safe and effective component of combination antiretroviral therapy. Methods. This double-blind, dose-ranging, phase 2 trial randomized subjects to receive 30 mg or 20 mg of vicriviroc or placebo once daily plus re-optimized background therapy containing a protease inhibitor with ritonavir. Subjects were adults infected with CCR5-tropic HIV who were experiencing failure of triple antiretroviral regimens. The primary end point was mean change in baseline log₁₀ HIV RNA level at 48 weeks, based on an intent-to-treat analysis. Results. One hundred fourteen persons received vicriviroc at 30 mg (n = 39), vicriviroc at 20 mg (n = 40), or placebo (n = 35). The mean change in baseline HIV RNA level at week 48 was -1.77 log₁₀ copies/mL for 30 mg of vicriviroc and -1.75 log₁₀ copies/mL for 20 mg of vicriviroc, compared with -0.79 log₁₀ copies/mL for placebo (P = .002 and P = .003, respectively, compared with placebo). Mean CD4 counts increased by 102, 136, and 63 cells/mm³ for 30 mg vicriviroc, 20 mg vicriviroc, and placebo, respectively (P = .260 and P = .039, respectively, compared with placebo). Rates of adverse events (mostly mild-to-moderate) were 111.4, 112.5, and 147.4 events per 100 subject-years, respectively. Conclusions. Vicriviroc administered with a protease inhibitor plus ritonavir-containing regimen shows potent antiretroviral and immunologic activity sustained over 48 weeks in treatment-experienced patients.