[Mitochondrial hepatic toxicity associated with antiretroviral treatment].
Highly active antiretroviral therapy (HAART) has become the gold standard treatment of HIV/AIDS infection. NRTI-related mitochondrial toxicity has been recognized as a serious adverse effect of HAART. The mechanisms underlying NRTI-induced mitochondriopathy involve the inhibition of the human DNA polymerase gamma mtDNA mutations and oxidative stress. The clinical spectrum of NRTI-related toxicity ranges from a subclinical disease e.g. mild hepatic abnormalities, to a rare life-threatening condition with lactic acidosis and hepatic insufficiency. In the latter, liver histology shows massive steatosis. Ultrastructural assessment of mitochondrial abnormalities may be of help to address the NRTI toxicity in poorly symptomatic patients. Efforts have been recently made to assess the clinical relevance of non-invasive tests including the evaluation of mtDNA or mitochondrial functions in peripheral blood mononuclear cells for the diagnosis of NRTI-associated toxicity.
Duong Van Huyen
Jean-Paul
JP
Service d'Anatomie Pathologique, Paris.
Batisse
Dominique
D
Bélair
Marie-France
MF
Bruneval
Patrick
P
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D000998:Antiviral Agents / Q000009:adverse effects*; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000473:pathology*
D000998:Antiviral Agents; D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase