Hepatic safety and tolerability of raltegravir among HIV patients coinfected with hepatitis B and/or C

Background: Potential liver toxicity is an important consideration for antiretroviral selection among patients coinfected with HIV and viral hepatitis (B and/or C). We sought to describe the hepatic safety profile of raltegravir in this population. Methods: Using data from HIV clinical cohorts at Johns Hopkins University and the University of North Carolina at Chapel Hill, we evaluated factors associated with liver enzyme elevations (LEEs) and calculated adverse event incidence rates for patients initiated on raltegravir-containing regimens prior to 1 January 2010. LEEs were graded according to Division of AIDS definitions. Results: During the study period, 456 patients received raltegravir - of whom 36% were hepatitis-coinfected (138 HCV, 17 HBV, 11 HBV+HCV). Coinfected patients were more likely to have baseline abnormal LEEs and developed severe (grade 3-4) LEEs at a rate 3.4x that of HIV-monoinfected patients (95% CI 1.28, 9.61). Among all participants, the incidence rate for first occurrence of severe LEEs was 5 per 100 person-years (95% CI 3, 7). In adjusted analyses, coinfected patients had a 2.7-fold increased hazard of severe LEEs (95% CI 1.03, 7.04). 60% of severe abnormalities occurred within 6 months after starting raltegravir; the drug was discontinued in 3 (1.3%) coinfected patients and 18 (6.2%) monoinfected patients. Conclusions: Compared with HIV-monoinfected patients, those with HIV-hepatitis coinfection are at increased hazard of developing LEEs on raltegravir, at a level similar to other antiretrovirals. Severe events were uncommon, rarely leading to raltegravir discontinuation. With appropriate monitoring, raltegravir-based therapy is safe in hepatitis-coinfected patients.