Hepatotoxicity of nucleoside reverse transcriptase inhibitors.
Hepatotoxicity is an adverse effect of all available classes of antiretrovirals, including nucleoside reverse transcriptase inhibitors (NRTI). A syndrome of hepatic steatosis and lactic acidosis has been recognized as a rare, potentially fatal complication since the advent of NRTI monotherapy in the early 1990s. Today, NRTI remain the backbone of antiretroviral combination regimens, and, with the success of current treatment strategies, exposure to two or more of these agents may occur over a number of years. Hepatic steatosis and lactic acidosis are accordingly being observed more frequently, along with a more recently recognized syndrome of chronic hyperlactatemia. These as well as other adverse effects of NRTI are mediated by inhibition of human DNA polymerase gamma, resulting in mitochondrial dysfunction in the liver and other tissues. Early recognition and intervention are essential to avert serious outcomes.
Montessori
Valentina
V
Clinical Assistant Professor, University of British Columbia, Vancouver, Canada. valm@hivnet.ubc.ca
Harris
Marianne
M
Montaner
Julio S G
JS
D019380:Anti-HIV Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors