Lactic acidosis secondary to nucleoside analogue antiretroviral therapy

A 53-year-old woman with newly diagnosed HIV infection was treated with the nucleoside analogue antiretroviral agents lamivudine and stavudine and the protease inhibitor indinavir. An illness characterized by severe lethargy, persistent nausea and vomiting, lactic acidosis, hyperglycemia, and microvesicular hepatic steatosis developed. Her symptoms improved gradually after withdrawal of the antiretroviral agents. The illness can be explained by mitochondrial dysfunction caused by inhibition of mitochondrial DNA (mtDNA) polymerase by the nucleoside analogues. The patient was successfully treated with nonnucleoside reverse transcriptase inhibitors, which lack affinity for mtDNA polymerase.