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

Abstract

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. 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. 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). 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.