TY - JOUR
T1 - Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in hiv-1-infected treatment-experienced patients
AU - Wilkin, Timothy J.
AU - Su, Zhaohui
AU - Krambrink, Amy
AU - Long, Jianmin
AU - Greaves, Wayne
AU - Gross, Robert
AU - Hughes, Michael D.
AU - Flexner, Charles
AU - Skolnik, Paul R.
AU - Coakley, Eoin
AU - Godfrey, Catherine
AU - Hirsch, Martin
AU - Kuritzkes, Daniel R.
AU - Gulick, Roy M.
PY - 2010/8/15
Y1 - 2010/8/15
N2 - 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 ≥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.
AB - 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 ≥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.
KW - CCR5 antagonist
KW - HIV-1
KW - antiretroviral therapy
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U2 - 10.1097/QAI.0b013e3181e2cba0
DO - 10.1097/QAI.0b013e3181e2cba0
M3 - Article
C2 - 20672447
AN - SCOPUS:77955006578
SN - 1525-4135
VL - 54
SP - 470
EP - 476
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 5
ER -