Symptomatic hyperlactataemia: an emerging complication of antiretroviral therapy

Background: Fatal lactic acidosis is a serious complication of therapy with nucleoside analogues. Objective: To examine symptomatic hyperlactataemia in HIV-infected adults t reated with antiretroviral drugs. Methods: In this prospective study, arterial blood lactate levels were meas ured in patients presenting with unexplained clinical symptoms. When these levels were high, functional respiratory tests (FRT) were carried out. Live r or muscle biopsies were further proposed. Incidences were calculated by c omparison with the entire cohort of patients treated in the department. Results: Fourteen HIV-infected adults treated with antiretroviral drugs wer e identified with symptomatic hyperlactataemia during a 2-year period follo w-up study. The incidence of hyperlactataemia was 0.8% per year but reached 1.2% if only patients treated with a regimen including stavudine were cons idered. Clinical symptoms included abnormal fatigue, tachycardia, abdominal pain, weight loss, peripheral neuropathy, and more specifically exercise-i nduced dyspnoea occurring despite effective antiretroviral treatment. FRT s howed a metabolic deviation towards anaerobiosis with a high lactate/pyruva te ratio. Ultrastructural mitochondrial abnormalities were seen in all four patients for whom this was examined. There was a marked decrease in comple x IV activity in muscle biopsies from four of five patients, consistent wit h a mitochondrial dysfunction. Evolution was favourable in 13 patients, pro bably because of an early diagnosis. Conclusions: Potentially fatal adverse events occurring during antiretrovir al treatment may be avoided by close monitoring of clinical signs and blood lactate levels. If other studies confirm that the cumulative long-term tox icity of antiretroviral drugs results from mitochondrial dysfunction, the i ncidence of hyperlactataemia and its clinical consequences may become more important. (C) 2000 Lippincott Williams & Wilkins.