Hepatic safety in subjects with HIV-1 and hepatitis C and/or B virus: a randomized, double-blind study of maraviroc versus placebo in combination with antiretroviral agents.

Background: One of the more clinically relevant co-morbidities in HIV-infected patients is the development of progressive liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV). In addition, hepatotoxicity has been observed with prolonged use of antiretroviral agents. Objective: To evaluate the hepatic safety of maraviroc in combination with other antiretroviral agents in HIV-1-infected subjects co-infected with HCV and/or HBV. Methods: In this 148-week randomized, double-blind, placebo- controlled, multicentre study (NCT01327547), subjects received maraviroc twice daily (n=70) or placebo (n=67) in combination with other antiretroviral agents. Primary endpoint: the percentage at week 48 of subjects with Grade 3 and Grade 4 ALT abnormalities, defined as > 5 x upper limit of normal (ULN) if baseline ALT <= ULN or > 3.5 x baseline if baseline ALT > ULN in the maraviroc versus the placebo arm. Results: At week 48, one subject in each group had met the primary endpoint definition. No subjects met protocol-defined liver stopping criteria and there were no cases of Hy's law or treatment-related hepatobiliary serious adverse events. No significant difference in change from baseline in enhanced liver fibrosis or hepatic elastography was observed between groups. Treatment-related hepatobiliary adverse events were reported in one and two subjects receiving maraviroc and placebo, respectively; discontinuations due to treatment-related AEs occurred in four and two subjects receiving maraviroc and placebo, respectively; two deaths were reported in the placebo group. Conclusions: The use of maraviroc does not increase hepatotoxicity in HIV-1-infected subjects co-infected with HCV and/or HBV through 48 weeks of treatment.