Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211.

TitlePhase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211.
Publication TypeJournal Article
Year of Publication2007
AuthorsGulick RM, Su Z, Flexner C, Hughes MD, Skolnik PR, Wilkin TJ, Gross R, Krambrink A, Coakley E, Greaves WL, Zolopa A, Reichman R, Godfrey C, Hirsch M, Kuritzkes DR
Corporate AuthorsAIDS Clinical Trials Group 5211 Team
JournalJ Infect Dis
Volume196
Issue2
Pagination304-12
Date Published2007 Jul 15
ISSN0022-1899
KeywordsAdult, Anti-Retroviral Agents, CCR5 Receptor Antagonists, CD4 Lymphocyte Count, Double-Blind Method, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Piperazines, Pyrimidines, Ritonavir, RNA, Viral, Viral Load
Abstract

BACKGROUND: Vicriviroc, an investigational CCR5 inhibitor, demonstrated short-term antiretroviral activity in a phase 1 study.

METHODS: The present study was a double-blind, randomized phase 2 study of vicriviroc in treatment-experienced, human immunodeficiency virus (HIV)-infected subjects experiencing virologic failure while receiving a ritonavir-containing regimen with an HIV-1 RNA level >or=5000 copies/mL and CCR5-using virus. Vicriviroc at 5, 10, or 15 mg or placebo was added to the failing regimen for 14 days, after which the antiretroviral regimen was optimized. The primary end point was the change in plasma HIV-1 RNA levels at day 14; secondary end points included safety/tolerability and HIV-1 RNA changes at week 24.

RESULTS: One hundred eighteen subjects were randomized with a median HIV-1 RNA level of 36,380 (4.56 log(10)) copies/mL and a median CD4 cell count of 146 cells/mm(3). At 14 days and 24 weeks, mean changes in HIV-1 RNA level (log(10) copies/mL) were greater in the vicriviroc groups (-0.87 and -1.51 [5 mg], -1.15 and -1.86 [10 mg], and -0.92 and -1.68 [15 mg]) than in the placebo group (+0.06 and -0.29) (P<.01). Grade 3/4 adverse events were similar across groups. Malignancies occurred in 6 subjects randomized to vicriviroc and in 2 to placebo.

CONCLUSIONS: In HIV-1-infected, treatment-experienced patients, vicriviroc demonstrated potent virologic suppression through 24 weeks. The relationship of vicriviroc to malignancy is uncertain. Further development of vicriviroc in treatment-experienced patients is warranted.

DOI10.1086/518797
Alternate JournalJ. Infect. Dis.
PubMed ID17570119
Grant ListAI-25859 / AI / NIAID NIH HHS / United States
AI-27661 / AI / NIAID NIH HHS / United States
AI-32783 / AI / NIAID NIH HHS / United States
AI-34853 / AI / NIAID NIH HHS / United States
AI-39439 / AI / NIAID NIH HHS / United States
AI-46370 / AI / NIAID NIH HHS / United States
AI-46381 / AI / NIAID NIH HHS / United States
AI-68634 / AI / NIAID NIH HHS / United States
AI-69411 / AI / NIAID NIH HHS / United States
AI-69418 / AI / NIAID NIH HHS / United States
AI-69419 / AI / NIAID NIH HHS / United States
AI-69423 / AI / NIAID NIH HHS / United States
AI-69424 / AI / NIAID NIH HHS / United States
AI-69432 / AI / NIAID NIH HHS / United States
AI-69434 / AI / NIAID NIH HHS / United States
AI-69450 / AI / NIAID NIH HHS / United States
AI-69465 / AI / NIAID NIH HHS / United States
AI-69471 / AI / NIAID NIH HHS / United States
AI-69472 / AI / NIAID NIH HHS / United States
AI-69474 / AI / NIAID NIH HHS / United States
AI-69494 / AI / NIAID NIH HHS / United States
AI-69495 / AI / NIAID NIH HHS / United States
AI-69501 / AI / NIAID NIH HHS / United States
AI-69502 / AI / NIAID NIH HHS / United States
AI-69532 / AI / NIAID NIH HHS / United States
AI-69556 / AI / NIAID NIH HHS / United States
K23 AI-55038 / AI / NIAID NIH HHS / United States
K24-AI-51966 / AI / NIAID NIH HHS / United States
M01-RR00044 / RR / NCRR NIH HHS / United States
M01-RR00046 / RR / NCRR NIH HHS / United States
M01-RR00047 / RR / NCRR NIH HHS / United States
M01-RR00051 / RR / NCRR NIH HHS / United States
M01-RR00052 / RR / NCRR NIH HHS / United States
M01-RR00096 / RR / NCRR NIH HHS / United States
P30-AI-45008 / AI / NIAID NIH HHS / United States
P30-AI-50410 / AI / NIAID NIH HHS / United States
U01-AI-68636 / AI / NIAID NIH HHS / United States