Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected treatment-experienced patients.
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.
Wilkin
Timothy J
TJ
Division of Infectious Diseases Weill Cornell Medical College, New York, NY, USA. tiw2001@med.cornell.edu
Su
Zhaohui
Z
Krambrink
Amy
A
Long
Jianmin
J
Greaves
Wayne
W
Gross
Robert
R
Hughes
Michael D
MD
Flexner
Charles
C
Skolnik
Paul R
PR
Coakley
Eoin
E
Godfrey
Catherine
C
Hirsch
Martin
M
Kuritzkes
Daniel R
DR
Gulick
Roy M
RM
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects*; D010919:Placebos / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D010879:Piperazines; D010919:Placebos; D011743:Pyrimidines; C486781:vicriviroc