Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected treatment-experienced patients

Abstract

Background: Vicriviroc, an investigational CCR5 antagonist, demonstrated short-term safety and antiretroviral activity.

Methods: Phase 2, double-blind, randomized study of vicriviroc in treatment-experienced subjects with CCR5-using HIV-1. Vicriviroc (5, 10, or 15 mg) or placebo was added to a failing regimen with optimization of background antiretroviral medications at day 14. Subjects experiencing virologic failure and subjects completing 48 weeks were offered open-label vicriviroc.

Results: One hundred eighteen subjects were randomized. Virologic failure (<1 log10 decline in HIV-1 RNA > or =16 weeks postrandomization) occurred by week 48 in 24 of 28 (86%), 12 of 30 (40%), 8 of 30 (27%), 10 of 30 (33%) of subjects randomized to placebo, 5, 10, and 15 mg, respectively. Overall, 113 subjects received vicriviroc at randomization or after virologic failure, and 52 (46%) achieved HIV-1 RNA <50 copies per milliliter within 24 weeks. Through 3 years, 49% of those achieving suppression did not experience confirmed viral rebound. Dual or mixed-tropic HIV-1 was detected in 33 (29%). Vicriviroc resistance (progressive decrease in maximal percentage inhibition on phenotypic testing) was detected in 6 subjects. Nine subjects discontinued vicriviroc due to adverse events.

Conclusions: Vicriviroc seems safe and demonstrates sustained virologic suppression through 3 years of follow-up. Further trials of vicriviroc will establish its clinical utility for the treatment of HIV-1 infection.

Trial registration: ClinicalTrials.gov NCT00082498.

Figures

Figure 1

Time to virologic failure (Intention-to-treat approach: follow-up censored at date of last available HIV-1 RNA measurement or at the date of dose increase to 15mg for subjects randomized to 5 mg) Note: Virologic failure is defined as 10 decline from baseline at or after 16 weeks after randomization.

Figure 2

Time to viral rebound (confirmed HIV-1 RNA >50 copies/mL) among subjects HIV-1 RNA suppressing to

Figure 3a and 3b

Vicriviroc susceptibility of HIV-1 from a subject for whom vicriviroc-containing antiretroviral therapy failed. Vicriviroc susceptibility was examined at week 0 (study entry) (a), and after 2 years of vicriviroc use by the PhenoSense entry assay (Monogram Biosciences, South San Francisco, CA) (21).