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. Issue 2 (April 2015)

• Record Type: Journal Article
• Authors: Rockstroh, Juergen K.; Soriano, Vicente; Plonski, Frank; Bansal, Meena; Fätkenheuer, Gerd; Small, Catherine B.; Asmuth, David M.; Pialoux, Gilles; Mukwaya, Geoffrey; Jagannatha, Shyla; Heera, Jayvant; Pineda, Juan A.
• Is Part Of: HIV clinical trials. Volume 16:Issue 2(2015)
• Page Start: 72
• Page End: 80
• Publication Date: 2015-04
• Subjects: Hepatitis B, -- Hepatitis C, -- Hepatotoxicity, -- HIV, -- Maraviroc; HIV Infections -- Chemotherapy -- Periodicals; AIDS (Disease) -- Chemotherapy -- Periodicals; HIV Infections -- Research -- Periodicals; AIDS (Disease) -- Research -- Periodicals; 616.979206105
• DOI: 10.1179/1528433614Z.0000000011
• Languages: English
• ISSNs: 1528-4336

Abstract

Abstract : 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 × upper limit of normal (ULN) if baseline ALT ≤ ULN or >3.5 × 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.