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

		SUMMARY: 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.

By Liz Highleyman

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.