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

TitleThree-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected treatment-experienced patients.
Publication TypeJournal Article
Year of Publication2010
AuthorsWilkin TJ, Su Z, Krambrink A, Long J, Greaves W, Gross R, Hughes MD, Flexner C, Skolnik PR, Coakley E, Godfrey C, Hirsch M, Kuritzkes DR, Gulick RM
JournalJ Acquir Immune Defic Syndr
Volume54
Issue5
Pagination470-6
Date Published2010 Aug
ISSN1944-7884
KeywordsAdult, Anti-HIV Agents, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Piperazines, Placebos, Pyrimidines, Treatment Outcome, Viral Load
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.

Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID20672447
PubMed Central IDPMC2917795
Grant ListAI- 69511 / AI / NIAID NIH HHS / United States
AI-25859 / AI / NIAID NIH HHS / United States
AI-27661 / AI / NIAID NIH HHS / United States
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