No increased risk of hepatotoxicity in long-term use of nonnucleoside reverse transcriptase inhibitors in HIV-infected patients.

OBJECTIVE: The aim of this study was to assess the incidence of hepatotoxicity in patients who had used nonnucleoside reverse transcriptase inhibitors (NNRTIs) for at least 3 years.

METHODS: The study group consisted of HIV-infected patients under follow-up at our clinic, who had continuously used an NNRTI-containing regimen (efavirenz or nevirapine) for at least 3 years. Patients who had used protease inhibitors (PIs) for the same time span constituted a control group. Hepatotoxicity was graded according to the modified AIDS Clinical Trial Group grading system, using alanine aminotransferase (ALT) as a marker.

RESULTS: One hundred and twenty-two patients on an NNRTI regimen and 54 PI-using patients were included in the analysis. The mean follow-up time was nearly 6 years. Eighteen NNRTI-using patients (14.8%) developed a clinically relevant (≥  grade II) event of hepatotoxicity during treatment; five of them (4.1%) developed severe hepatotoxicity (≥  grade III). No significant difference in the hepatotoxicity rate was seen between NNRTI- and PI-using patients (14.8 vs. 18.5%, respectively; P = 0.52) or between patients using efavirenz and nevirapine (13.8% vs. 16.7%, respectively; P = 0.51). A hepatitis C virus (HCV) coinfection was associated with an increased risk of the development of hepatotoxicity during NNRTI therapy [odds ratio (OR) 1.83; 95% confidence interval (CI) 1.33-4.24; P < 0.01]. Finally, we observed that more hepatotoxic events occurred during the first year of NNRTI therapy compared with the entire period after 1 year (6.6 vs. 2.8 events, respectively, per 100 person-years of treatment; P = 0.04).

CONCLUSIONS: Long-term NNRTI use was not associated with a higher risk of clinically significant liver toxicity in patients who had been treated with NNRTI for at least 3 years.