Dossier : Oxidative stress pathologies and antioxidants Could antioxidant supplementation reduce antiretroviral therapy-induced chronic stable hyperlactatemia? O. Lopez a , D. Bonnefont-Rousselot b , M. Edeas c , J. Emerit a, *, F. Bricaire a a Service des Maladies Infectieuses et Tropicales, Groupe Hospitalier Pitié-Salpêtrière (AP-HP), 47 boulevard de l’Hôpital, 75651 Paris cedex 13, France b Laboratoire de Biochimie B, Groupe Hospitalier Pitié-Salpêtrière, 47 boulevard de l’Hôpital, 75651 Paris, France c Service de Biochimie, Hôpital Béclère, 157 rue de la Porte Trivaux, 92100 Clamart, France and la Société Française des Antioxydants, 15, rue de la Paix, 75002 Paris, France Received 24 September 2002; accepted 7 November 2002 Abstract Objective.– To determine if asymptomatic stable chronic hyperlactatemia in human immunodeficiency virus (HIV)-infected patients under highly active antiretroviral therapy (HAART, including nucleoside analog reverse transcriptase inhibitors (NRTI)) could be improved by antioxidant supplementation. Design.– To match two groups of patients taking NRTI for at least 24 months: 15 without and 15 with antioxidant supplementation (vitamin E, b-carotene, N-acetylcysteine, selenium, Gingko biloba extracts and nutritional supplements). For both the groups, the supplemen- tation by antioxidants or its lack was carefully assessed. Venous lactatemia, blood oxidative stress markers (plasma lipid peroxidation, enzymatic and non-enzymatic antioxidants), CDC revisited classification, CD4 count and viral load, NRTI (with or without stavudine) and other antiretroviral drugs used, lipoatrophy, central fat accumulation were assessed. Results.– Patients were not statistically different with respect to the CDC classification, CD4 count, viral load and characteristics of antiretroviral therapy. Blood oxidative stress markers, i.e. vitamin E, vitaminA and b-carotene tended to be higher in the supplemented group. The difference observed in venous lactate concentration between the two groups was significant (1.37 ± 0.10 vs. 1.82 ± 0.19 mmol/l in the supplemented and non-supplemented groups, respectively P = 0.04). Conclusion.– Antioxidant supplementation improves the asymptomatic stable chronic hyperlactatemia observed in HIV-infected patients taking HAART including NRTI for a long time. Controlled studies are needed to demonstrate the efficacy of this supplementation on mitochondrial toxicity observed during HAART and the possible usefulness of its combination with mitochondrial cofactors like carnitine, riboflavine, coenzyme Q, a-lipoic acid. © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Nucleoside reverse transcriptase inhibitors; Mitochondrial toxicity; Oxidative stress 1. Introduction Nucleoside analog reverse transcriptase inhibitors (NRTI) remain a cornerstone of antiretroviral therapy for human immunodeficiency virus (HIV) infection, and are widely used in highly active antiretroviral therapy (HAART). These agents inhibit HIV replication, and can also inhibit the human DNA polymerase c, and thereby, replication of mito- chondrial DNA, leading to depletion of mitochondrial DNA and drug toxicity [3]. Mitochondrial toxicity is at least partially responsible for adverse effects such as lactic acidosis, hepatic steatosis, myopathy, cardiomyopathy, peripheral neuropathy, pancre- atitis, and also the lipodystrophysyndrome [4,9]. As lactate is the product of anaerobic glycolysis, hyperlactatemia in nor- mal aerobic conditions indicates mitochondrial dysfunction [8]. Chronic, asymptomatic hyperlactatemia is common, in patients taking HAART. In a study based on the 516 patient- years of observation [8], asymptomatic hyperlactatemia was Abbreviations: HAART, highly active antiretroviral therapy; NRTI, nu- cleoside analog reverse transcriptase inhibitors; PI, protease inhibitors; NNRTI, non-nucleoside analog reverse transcriptase inhibitors. * Corresponding author. E-mail address: emerit@wanadoo.fr (J. Emerit). Biomedicine & Pharmacotherapy 57 (2003) 113–116 www.elsevier.com/locate/biopha © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. DOI: 10.1016/S0753-3322(03)00017-9