Depletion of mitochondrial DNA in liver under antiretroviral therapy with didanosine, stavudine, or zalcitabine

• DOI: 10.1002/hep.20074
• Publication Date: 2004-02-03T17:05:53Z
• Authors: Ulrich A. Walker; Jochen Bäuerle; Montse Laguno; Javier Murillas; Stefan Mauss; Günther Schmutz; Bernhard Setzer; Rosa Miquel; José M. Gatell; Josep Mallolas
• Keywords: Didanosine; Stavudine; Zalcitabine; Mitochondrial toxicity; Hyperlactatemia; Abacavir

The “D drug” HIV reverse-transcriptase inhibitors zalcitabine, didanosine, and stavudine are relatively strong of polymerase-gamma compared with the “non-D drugs” zidovudine, lamivudine, abacavir. D drugs deplete mitochondrial DNA (mtDNA) in cultured hepatocytes. This mtDNA depletion is associated an increased vitro production lactate. To investigate origin hyperlactatemia HIV-infected patients effects antiretroviral therapy on liver mtDNA, we biopsied tissue from 94 individuals chronic hepatitis C virus (HCV) infection. Eighty subjects were coinfected HIV. Serum lactate was measured at time biopsy. Hepatic histology centrally assessed. Liver content receiving biopsy (n = 34) decreased by 47% ( P <.0001) those without 35). Aside a possible association between HCV genotype I status multivariate analysis, there no other virologic, immunologic, histologic, demographic or treatment-related variables that could explain depletion. Lactate above upper limit normal only three patients, all whom treated drugs. each them lower than any non-D drug patient significantly .017) depleted In conclusion, treatment hepatic Moderate does not necessarily lead to hyperlactatemia, but more pronounced decreases may be important contributor elevation. (Hepatology 2004;39:311-317.)