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Experimental CCR5 Antagonist Vicriviroc Appears Safe and Well Tolerated in HIV/HCV Coinfected Patients

The investigational CCR5 antagonist vicriviroc, now undergoing clinical trials for treatment of HIV, appeared to be safe and well tolerated in a 28 day study of individuals with HIV/HCV coinfection, according to a study described in the January 1, 2010 Journal of Acquired Immune Deficiency Syndromes. Vicriviroc did not affect hepatitis C virus (HCV) levels, but it also did not lower HIV viral load as intended.

HIV can use 2 different surface co-receptors -- CCR5 and CXCR4 -- to gain entry into CD4 cells. CCR5 antagonists, including the approved antiretroviral drug maraviroc (Selzentry) and the experimental candidate vicriviroc, are intended to work against CCR5-tropic strains of the virus. Individuals considering these drugs are screened using a tropism assay to ensure that they carry only CCR5-tropic HIV, not CXCR4-tropic or dual/mixed-tropic strains.

CCR5 antagonists are a novel class of drugs and the potential ramifications of their use are not yet clear, since the CCR5 receptor plays a role in immune recognition and response that is not fully understood. As with CD4 cells susceptible to HIV infection, CD8 T-cells involved in clearing hepatitis C virus (HCV) also carry the CCR5 receptor on their surface.

In the present study, Gerd Fätkenheuer from the University of Cologne in Germany and colleagues evaluated the short-term safety of vicriviroc in people with HIV/HCV coinfection.

This randomized, double-blind trial included 28 HIV/HCV coinfected patients with compensated liver disease and plasma HIV RNA < 400 copies/mL who were taking combination antiretroviral therapy regimens containing a ritonavir-boosted protease inhibitor.

Participants were randomly assigned to receive vicriviroc at doses of 5, 10, or 15 mg/day or else placebo for 28 days. Clinical and laboratory evaluations were performed 21 days after the treatment period.

Results

• Treatment with vicriviroc resulted in no clinically meaningful changes in HCV or HIV viral load.
• There were also no changes in any measured immune parameters.
• Adverse events occurred with equal frequency in the vicriviroc and placebo groups.
• 1 patient in the 10 mg vicriviroc group and 1 placebo recipient reported liver transaminase (ALT and AST) elevations of grade 1 or higher.
• Vicriviroc plasma concentrations in this coinfected group were similar to those observed in healthy uninfected volunteers.

"Short-term treatment with vicriviroc as part of a ritonavir-containing protease inhibitor-based regimen was safe and well tolerated in HIV/HCV coinfected subjects," the study authors concluded. "HIV/HCV coinfection also did not affect vicriviroc pharmacokinetics."

1/12/10

Reference

G Fätkenheuer, C Hoffmann, J Slim, and others. Short-Term Administration of the CCR5 Antagonist Vicriviroc to Patients with HIV and HCV Coinfection Is Safe and Tolerable. Journal of Acquired Immune Deficiency Syndromes 53(1): 78-85 (Abstract). January 1, 2010.