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

Landovitz, Raphael J. ; Angel, Jonathan B. ; Hoffmann, Christian ; Horst, Heinz ; Opravil, Milos ; Long, Jianmin ; Greaves, Wayne ; Fätkenheuer, Gerd

In: Journal of Infectious Diseases, 2008, vol. 198, no. 8, p. 1113-1122

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    Titre
    • Phase II Study of Vicriviroc versus Efavirenz (both with Zidovudine/Lamivudine) in Treatment-Naive Subjects with HIV-1 Infection
    Auteur
    • Landovitz, Raphael J.. Schering-Plough Research Institute, Kenilworth, New Jersey
    • Angel, Jonathan B.. Department of Medicine, University of Ottawa, Ottawa, Canada
    • Hoffmann, Christian. Second Department of Medicine, University of Schleswig-Holstein, Campus Kiel
    • Horst, Heinz. Second Department of Medicine, University of Schleswig-Holstein, Campus Kiel
    • Opravil, Milos. Division of Infectious Diseases, University Hospital Zurich, Zurich, Switzerland
    • Long, Jianmin. Schering-Plough Research Institute, Kenilworth, New Jersey
    • Greaves, Wayne. Schering-Plough Research Institute, Kenilworth, New Jersey
    • Fätkenheuer, Gerd. Department 1 of Internal Medicine, University of Cologne, Cologne, Germany
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Journal of Infectious Diseases, 2008, vol. 198, no. 8, p. 1113-1122. The University of Chicago Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:294892
    Summary
    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 comparison of 3 dosages of VCV with placebo in treatment-naive subjects infected with CCR5-using HIV-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 from baseline values by 0.07 log10 copies/mL in the placebo arm, 0.93 log10 copies/mL in theVCV25 mg 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 25 mg/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. Conclusion. VCV administered with dual NRTIs in treatment-naive subjects with HIV-1 infection had increased rates of virologic failure, compared with efavirenz plus dual NRTIs. No treatment-limiting toxicity was observed. Study of higher doses of VCV as part of combination therapy is warranted