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.
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.



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.



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.



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.



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.



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.
Juergen K
JK
Rockstroh
Vicente
V
Soriano
Frank
F
Plonski
Meena
M
Bansal
Gerd
G
Fätkenheuer
Catherine B
CB
Small
David M
DM
Asmuth
Gilles
G
Pialoux
Geoffrey
G
Mukwaya
Shyla
S
Jagannatha
Jayvant
J
Heera
Juan A
JA
Pineda
D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D065100:CCR5 Receptor Antagonists / Q000008:administration & dosage; D060085:Coinfection; D003510:Cyclohexanes / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000187:drug effects; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D010919:Placebos; D014230:Triazoles / Q000008:administration & dosage
D044966:Anti-Retroviral Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D010919:Placebos; D014230:Triazoles; D000077592:Maraviroc
HIV,; Hepatitis B,; Hepatitis C,; Hepatotoxicity,; Maraviroc