Hepatotoxicity of antiretroviral therapy in HIV-infected patients

Objective. To estimate the rate and degree of hepatotoxicity in patients receiving different antiretroviral therapy (ART) regimens for further improvement of therapeutic approaches. Subjects and methods. The rate of hepatotoxicity during the first 48 weeks of ART was analyzed in 720 adult patients with HIV infection. Hepatotoxicity was estimated using the international adverse drug reaction scale on the basis of clinical symptoms and time-course of changes in the ALT and AST levels measured before and 1, 3, 6, and 12 months after ART. Results. The levels of liver enzymes were most frequently elevated after 3-6 months of ART regardless of its regimen. The rate of severe (grade 3) hepatotoxicity increased in proportion to the time antiretroviral drugs were taken. The use of protease inhibitors (PIs) did not virtually affect the rate of an elevation in the level of transaminases while that of nonnucleoside reverse transcriptase inhibitors (NNRTIs) caused hepatotoxicity in more than half of the patients at 6 months of ART. Elevated baseline ALT levels and the presence of chronic viral hepatitis were the most unfavorable factors of hepatotoxicity during ART particularly in patients receiving NNRTIs. Women with a CD4+ lymphocyte count of more than 250 cells/ßl and men with this indicator greater than 400 cells/ßl should be considered as a hepatotoxicity risk group before nevirapine intake. Conclusion. In addition to 2 NNRTIs, a PI should be incorporated in an ART regimen for patients with chronic viral hepatitis or elevated transaminase levels. In so far as each class contains drugs with a higher or lower effect hepatotoxic effect, it is crucially important to choose ART regimens strictly individually with regard to all patient characteristics.

HIV infection, antiretroviral therapy, hepatotoxicity, chronic viral hepatitides