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Phase II study of vicriviroc versus efavirenz (both with zidovudine/lamivudine) in treatment-naive subjects with HIV-1 infection


Landovitz, R J; Angel, J B; Hoffmann, C; Horst, H; Opravil, M; Long, J; Greaves, W; Fätkenheuer, G (2008). Phase II study of vicriviroc versus efavirenz (both with zidovudine/lamivudine) in treatment-naive subjects with HIV-1 infection. Journal of Infectious Diseases, 198(8):1113-1122.

Abstract

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 log(10) copies/mL in the placebo arm, 0.93 log(10) copies/mL in the VCV 25 mg arm, 1.18 log(10) copies/mL in the VCV 50 mg arm, and 1.34 log(10) copies/mL in the VCV 75 mg arm ([Formula: see text] 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. CONCLUSIONS: 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.

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 log(10) copies/mL in the placebo arm, 0.93 log(10) copies/mL in the VCV 25 mg arm, 1.18 log(10) copies/mL in the VCV 50 mg arm, and 1.34 log(10) copies/mL in the VCV 75 mg arm ([Formula: see text] 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. CONCLUSIONS: 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:22 Dec 2008 10:06
Last Modified:05 Apr 2016 12:42
Publisher:University of Chicago Press
ISSN:0022-1899
Additional Information:2008 by the Journal of Infectious Diseases
Publisher DOI:10.1086/592052
PubMed ID:18783318
Permanent URL: http://doi.org/10.5167/uzh-8154

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