Prospective, open-label comparative study of liver toxicity in an unselected population of HIV-infected patients treated for the first time with efavirenz or nevirapine

Objective: To compare the two nonnucleoside reverse transcriptase inhibitors (NNRTIs) when first introduced in an antiretroviral regimen, a prospective open-label assessment of the frequency, severity, risk factors, and outcome of hepatotoxicity was performed. Method: Liver enzymes were followed-up during 18 months in patients who received efavirenz (EFV; 324 patients) or nevirapine (NVP; 299). Results: The two study groups were comparable, except for the lower baseline CD4+ count found in the EFV group. No differences were found when considering the type and duration of eventual prior anti-HIV therapy; frequency and length of protease inhibitors, methadone, or anti-tubercular drug use; HCV-HBV co-infection; other hepatobiliary disorders; and alcohol-drug abuse. The frequency of overall and first-month drug interruption proved similar in the two study groups. A hepatotoxicity characterized by at least a 2-fold increase of transaminases versus baseline was significantly linked with NVP, and the number of patients showing hepatotoxicity tended to a reduction in the EFV group. Also the time to peak transaminase alterations was shorter in the NVP group. All significant differences regarding liver-pancreatic toxicities were controlled per eventual baseline hepatobiliary-pancreatic diseases, HIV stage, and concurrent drug therapies. Discussion: Hepatotoxicity is a significant concern in the setting of antiretroviral-treated HIV disease. NVP-based HAART may be more hepatotoxic than EFV-based HAART, and a role is played by chronic liver disorders. Although concurrent hepatobiliary disorders and the possible hepatotoxicity of antiretrovirals do not represent contraindications to nonnucleoside inhibitor use, strict monitoring is recommended.