We describe a 49-year-old man with human immunodeficiency virus infection and stable chronic renal insufficiency who developed acute oliguric renal failure and severe lactic acidosis and who died several weeks after tenofovir was added to an antiretroviral regimen that included didanosine. Although the role of tenofovir in precipitating acute renal failure is unclear, progressive accumulation of the drug and pharmacologic interaction that caused increased levels of didanosine were the likely antecedents of increased mitochondrial toxicity that led to lactic acidosis.

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