625   Hyperlactatemia in HIV-Infected Patients: The Role of NRTI Treatment.

S. M. E. Vrouenraets, M. Treskes, R. M. Regez, N. Troost, H. M. Weigel, P. H. J. Frissen, and K. Brinkman*. Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.

Background:Long-term treatment with NRTIs can induce mitochondrial dysfunction, most severely represented by lactic acidosis. Diagnostic tests for mitochondrial dysfunction are lacking, and it is unclear whether lactic acidosis is preceded by a period of (asymptomatic) hyperlactatemia. The objectives of this study were to determine the occurrence of hyperlactatemia in HIV-infected patients on NRTI treatment and to evaluate the possible risk factors.

Methods:Cross-sectional analysis of lactic-acid levels in asymptomatic HIV-infected patients. Hyperlactactemia was considered mild if between 2.1—5 mmol/l and serious if >5 mmol/l, and lactic acidosis was defined as lactic acid >5 mmol/l and bicarbonate <20 mmol/l. Possible risk factors, such as current and preceding NRTI treatment as well as concurrent liver disease, were analyzed.

Results:223 asymptomatic HIV-infected patients were studied, including 173 patients (78%) on NRTI treatment. Lactic-acid level was normal in 135 (78%) on NRTI treatment and in 46 (92%) without treatment. Mild hyperlactatemia was found in 37/173 (21%) treated and 4/50 (8%) untreated patients (c²p < 0.05). One treated patient had serious hyperlactatemia without acidosis but retested normal 2 weeks later. In multivariate analysis, an increased risk was found for treatment combinations containing d4T (OR 10.0; 2.5—39.6), AZT (OR 6.8; 1.6—28.4) and/or abacavir (OR 6.7; 1.5—30.5), but not for DDI-, 3TC- or DDC-containing treatment regimens. There was no statistical association between lactic-acid level and positive hepatitis serology or elevated liver enzymes (ALT). Longitudinal observation showed wide inter- and intraindividual fluctuations, while elevated lactate levels were not consistent in the same individuals.

Conclusions:Although there was a clear correlation between hyperlactatemia and NRTI treatment, the value of lactate measurement for individual treatment monitoring remains obscure.