Severe lactic acidosis in HIV-infected patients treated with nucleosidic reverse transcriptase analogs: a report of 9 cases

Symptomatic lactic acidosis requiring intensive care is a rare and severe adverse event related to the mitochondrial toxicity of the nucleoside analog reverse transcriptase inhibitors (NRTIs). We retrospectively investigated the clinical and biological features of HIV-infected patients who developed severe lactic acidosis syndrome at the University teaching hospital of Bordeaux and the regional community hospital, during 1996-2000. Nine patients were identified (incidence: 0,9/1000 NRTI treated patient-years), 4 men and 5 women with a median age of 36 years. They had a moderate immunodeficiency (median CD4+ T lymphocyte counts: 197/mm(3)) and only one of them presented a virological failure. The causes of hospital admission were abdominal pain (n = 6), dyspnea (n = 6), asthenia (n = 5), jaundice (n = 4), and vomiting (n = 2). Hepatomegaly was present in 6 patients. Lactic acidosis was found in all cases: median pH: 7.28, bicarbonate: 12 mmol/l, anion gap: 27 mEq/l, plasma lactic acid: 13 mmol/l. Cytolysis (n = 8), cholestasis (n = 6), hepatic failure (n = 4), rhabdomyolysis (n = 4) and pancreatitis (n = 2), were also present. Despite medical intensive care, seven patients died. The only two post-mortem examinations revealed severe hepatic steatosis. Median duration of NRTI therapy was 4 years. At presentation, five patients were receiving lamivudine, five didanosine, four stavudine and three zidovudine. Six patients were coinfected by HCV and/or HBV, four had chronic renal failure and five an immediately preceding infectious disease. The prognosis of lactic acidosis is severe. Nucleosid-analog therapy needs clinical and biological monitoring, specially in patients with comorbidities.