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.
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
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
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
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
antiretroviral therapy regimens containing a ritonavir-boosted
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.
with vicriviroc resulted in no clinically meaningful
changes in HCV or HIV viral load.
were also no changes in any measured immune parameters.
events occurred with equal frequency in the vicriviroc
and placebo groups.
patient in the 10 mg vicriviroc group and 1 placebo
recipient reported liver transaminase (ALT and
AST) elevations of grade 1 or higher.
plasma concentrations in this coinfected group
were similar to those observed in healthy uninfected
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."
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.