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 (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. 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.
RCT Entities:
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 (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. 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.
Authors: Timothy J Wilkin; Zhaohui Su; Amy Krambrink; Jianmin Long; Wayne Greaves; Robert Gross; Michael D Hughes; Charles Flexner; Paul R Skolnik; Eoin Coakley; Catherine Godfrey; Martin Hirsch; Daniel R Kuritzkes; Roy M Gulick Journal: J Acquir Immune Defic Syndr Date: 2010-08 Impact factor: 3.731
Authors: Zahra F Parker; Shilpa S Iyer; Craig B Wilen; Nicholas F Parrish; Kelechi C Chikere; Fang-Hua Lee; Chuka A Didigu; Reem Berro; Per Johan Klasse; Benhur Lee; John P Moore; George M Shaw; Beatrice H Hahn; Robert W Doms Journal: J Virol Date: 2012-12-26 Impact factor: 5.103
Authors: Robert A Ogert; Lei Ba; Yan Hou; Catherine Buontempo; Ping Qiu; Jose Duca; Nicholas Murgolo; Peter Buontempo; Robert Ralston; John A Howe Journal: J Virol Date: 2009-09-23 Impact factor: 5.103