Hepatic safety and tolerability in the maraviroc clinical development program
- 13 November 2010
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in AIDS
- Vol. 24 (17), 2743-2750
- https://doi.org/10.1097/qad.0b013e32833f9ce2
Abstract
Maraviroc is the first CCR5 antagonist to be approved for the treatment of HIV-1 infection. It is generally well tolerated, with a similar side-effect profile to placebo in controlled studies. Many agents used to treat HIV disease are associated with the potential for hepatotoxicity. The hepatic effects of maraviroc were analyzed across all Pfizer-sponsored maraviroc clinical trials, in which 2350 volunteers received maraviroc. Although sporadic hepatic enzyme abnormalities were reported in 34 phase 1/2a studies of up to 28-day duration, they demonstrated no dose relationship or association with hyperbilirubinemia. In the four phase 2b/3 studies in antiretroviral -naive and antiretroviral-experienced patients, there was no significant imbalance in hepatic enzyme abnormalities or hepatobiliary adverse events in maraviroc versus comparator arms up to week 96. The findings were similar in patients coinfected with hepatitis B and/or C virus, although the number of coinfected patients was small. No patient met the strict definition for Hy's Law. Two participants reported severe hepatotoxicity and although other potential causes were present, the contribution of maraviroc to these events could not be excluded. This analysis suggests that maraviroc does not present significant risks to hepatic safety when taken at the recommended doses in the populations studied.This publication has 15 references indexed in Scilit:
- Hepatotoxicity Observed in Clinical Trials of Aplaviroc (GW873140)Antimicrobial Agents and Chemotherapy, 2008
- Antiretroviral drugs and liver injuryAIDS, 2008
- Liver-Related Deaths in Persons Infected With the Human Immunodeficiency VirusArchives of Internal Medicine, 2006
- CCR5 deficiency exacerbates T-cell-mediated hepatitis in miceJournal of Hepatology, 2005
- Drug-Induced Liver Injury Associated with the Use of Nonnucleoside Reverse-Transcriptase InhibitorsClinical Infectious Diseases, 2004
- Grade 4 Events Are as Important as AIDS Events in the Era of HAARTJAIDS Journal of Acquired Immune Deficiency Syndromes, 2003
- Risk of severe hepatotoxicity associated with antiretroviral therapy in the HIV-NAT Cohort, Thailand, 1996–2001AIDS, 2003
- Severe Hepatotoxicity During Combination Antiretroviral Treatment: Incidence, Liver Histology, and OutcomeJAIDS Journal of Acquired Immune Deficiency Syndromes, 2003
- Incidence of and Risk Factors for Severe Hepatotoxicity Associated with Antiretroviral Combination TherapyThe Journal of Infectious Diseases, 2002
- Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infectionAIDS, 2000