Lack of Hepatotoxicity Associated With Nonnucleoside Reverse Transcriptase Inhibitors

Abstract

Nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine, have been associated with hepatotoxicity. We performed a retrospective study to determine the incidence of NNRTI hepatotoxicity in a group of HIV-infected patients from a New York City practice. These patients are predominantly homosexual white males. We also analyzed the effect of coinfection with hepatitis B (HBV) or hepatitis C (HCV) virus. In total, 272 patients received NNRTIS: 40 (15%) received delavirdine, 91 (33%) received efavirenz, and 141 (52%) received nevirapine. Of the patients with known hepatitis status, 18 of 190 (9%) were coinfected with HBV, and 24 of 205 were coinfected (12%) with HCV. The overall rate of grade 3 to 4 elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) was 3 of 272 (1.1%) and did not differ significantly among the three NNRTIs. HBV or HCV was not associated with a significant increase in AST or ALT elevations. We conclude that NNRTIs are relatively free from hepatotoxicity in this population, despite the presence of coinfection with HBV or HCV.

Long-term efficacy and safety of treatment with nevirapine plus nucleoside reverse transcriptase inhibitors for HIV-1 infection: An eight-years follow-up

“…The significance of the ␥-GT increase remains obscure, but it has been hypothesized to represent a marker of microsomial induction rather than a liver damage sign. As in other studies [19,22,23], our HIV and HCV/HBV co-infected patients have not shown significant increase of ALT and AST levels. The 8-years follow-up highlights that liver enzyme levels of HBV/HCV and HIV co-infected patients are similar with those of patients without hepatitis, in spite of higher baseline levels.…”

“…In collusion with other studies [1,18,19], we have observed that NVP-treatment causes more often the increase of ␥-GT than ALT and AST: after two years, ␥-GT levels reached a plateau in patients without hepatitis. This trend has been pointed out also by the Murphy et al meta-analysis [19].…”

“…This trend has been pointed out also by the Murphy et al meta-analysis [19]. The significance of the ␥-GT increase remains obscure, but it has been hypothesized to represent a marker of microsomial induction rather than a liver damage sign.…”

Hepatotoxicity of antiretrovirals: Incidence, mechanisms and management

“…In some series, the incidence of liver toxicity is not higher compared to other antiretrovirals [41,43,44]. This is especially true in populations with a low prevalence of chronic HCV infection [43].…”

Chronic Liver Disease in the Human Immunodeficiency Virus Patient

“…64,83 Overall, however, NNRTIs have a low rate of clinically significant hepatotoxicity. 84,85 Among PIs, ritonavir and ritonavir-boosted HAART regimens have been most studied and identified as independent risk factors for the development of hepatotoxicity. Wit and colleagues 86 documented ritonavir (full-dose therapy) as an independent risk factor, with a 5.8-fold increased risk of developing grade 4 liver enzyme elevations.…”