Asymptomatic hyperlactataemia: predictive value, natural history and correlates.

Background: The significance of asymptomatic hyperlactataemia is unknown.

Methods: We measured serial lactate levels in a group of HIV-infected subjects. Objectives were to identify covariates associated with hyperlactataemia, and to explore the natural history of hyperlactataemia.

Results: Overall, 1487 lactate measurements were performed on 396 subjects; 299 subjects had serial lactate testing, with a median of four performed per patient (range: 2-16). At study entry, lactate was >2.4 mmol/l in 6% of subjects and >3.6 mmol/l in 1%. A multiple logistic regression analysis revealed that cholesterol and current stavudine were the only predictors of hyperlactataemia. Lactate levels were highly reproducible both for short-term (within 3 months) and long-term (>1 year) follow-up. During the study period, 16 subjects were identified with sustained hyperlactataemia; 12/16 remained asymptomatic after a median of 210 days (30-585), and four developed symptoms suggestive of lactic acidosis syndrome. In three of the four, asymptomatic hyperlactataemia had preceded the onset of symptoms by 18-122 days. A longitudinal model showed a rapid rise of lactate levels from 0 to 12 months on nucleoside reverse transcriptase inhibitor (NRTI) and then stabilization. Lactate levels did not correlate with baseline or on-study development of lipoatrophy.

Conclusions: Even when optimal methods of collection are used, asymptomatic hyperlactataemia does exist and could be sustained in a subset of NRTI-treated subjects for as long as 585 days. A subset of these subjects became symptomatic, after as long as 122 days of asymptomatic hyperlactataemia. Asymptomatic hyperlactataemia is not predictive of lipoatrophy.