Antiretroviral therapy-related hepatotoxicity: predictors and clinical management

Severe hepatotoxicity develops in 5-10% of people with HIV infection in the first 12 months following initiation of highly-active antiretroviral therapy (HAART), with continuing risk in subsequent years. The major risk factors for severe hepatotoxicity are underlying chronic viral hepatitis, abnormal baseline levels of serum hepatic transaminases, and nevirapine or high-dose ritonavir-containing antiretroviral therapy regimens. The vast majority of severe hepatotoxicity cases are not associated with development of symptoms of acute hepatitis or other adverse hepatic outcomes and resolve within a few months. Antiretroviral therapy should be discontinued in association with grade 4 elevations in serum hepatic transaminase measurements, hyperlactataemia, symptoms of acute hepatitis, or features of drug hypersensitivity.