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

• Published in: The Journal of infectious diseases Vol. 196; no. 2; pp. 304 - 312
• Main Authors: Gulick, Roy M., Su, Zhaohui, Flexner, Charles, Hughes, Michael D., Skolnik, Paul R., Wilkin, Timothy J., Gross, Robert, Krambrink, Amy, Coakley, Eoin, Greaves, Wayne L., Zolopa, Andrew, Reichman, Richard, Godfrey, Catherine, Hirsch, Martin, Kuritzkes, Daniel R.
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 15.07.2007; University of Chicago Press
• Subjects: Adult; AIDS; Anti-Retroviral Agents - adverse effects; Anti-Retroviral Agents - therapeutic use; Antiretrovirals; CCR5 Receptor Antagonists; CD4 Lymphocyte Count; Clinical trials; Dosage; Double-Blind Method; Drug Therapy, Combination; Female; HIV 1; HIV Infections - drug therapy; HIV Infections - prevention & control; HIV-1 - classification; HIV-1 - drug effects; HIV/AIDS; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Humans; Male; Middle Aged; Piperazines - adverse effects; Piperazines - therapeutic use; Placebos; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Receptors; Ritonavir - therapeutic use; RNA; RNA, Viral - analysis; RNA, Viral - drug effects; Viral Load; Virology; Viruses
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1086/518797

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 ⩾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 level changes at week 24. Results. One hundred eighteen subjects were randomized with a median HIV-1 RNA level of 36,380 (4.56 log10) copies/mL and a median CD4 cell count of 146 cells/mm3. At 14 days and 24 weeks, mean changes in HIV-1 RNA level (log10 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.