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.

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.

• Authors: Roy M Gulick, Zhaohui Su, Charles Flexner, Michael D Hughes, Paul R Skolnik, Timothy J Wilkin, Robert Gross, Amy Krambrink, Eoin Coakley, Wayne L Greaves, Andrew Zolopa, Richard Reichman, Catherine Godfrey, Martin Hirsch, Daniel R Kuritzkes, AIDS Clinical Trials Group 5211 Team
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 196 Issue 2 Pg. 304-12 (Jul 15 2007) ISSN: 0022-1899 [Print] United States
• PMID: 17570119 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Retroviral Agents
• CCR5 Receptor Antagonists
• Piperazines
• Pyrimidines
• RNA, Viral
• Ritonavir
• vicriviroc

Topics

• Adult
• Anti-Retroviral Agents (adverse effects, therapeutic use)
• CCR5 Receptor Antagonists
• CD4 Lymphocyte Count
• Double-Blind Method
• Drug Therapy, Combination
• Female
• HIV Infections (drug therapy, prevention & control)
• HIV-1 (classification, drug effects)
• Humans
• Male
• Middle Aged
• Piperazines (adverse effects, therapeutic use)
• Pyrimidines (adverse effects, therapeutic use)
• RNA, Viral (analysis, drug effects)
• Ritonavir (therapeutic use)
• Viral Load