Oral Presentation: PS5 - Adverse Effects of HIV Therapy PS5/6 - Uridine for the treatment of HAART-associated lipodystrophy - a randomized, double-blind, placebo-controlled trial

Sutinen J.1, Walker U.A.2, Häkkinen A.-M.3, Ristola M.4, Yki-Järvinen H.5

1Helsinki University Central Hospital, Division of Infectious Diseases and Diabetes, Department of Medicine, Helsinki HUS, Finland, 2Medizinische Universitätsklinik, Department of Rheumatology and Clinical Immunology, Freiburg, Germany, 3Helsinki University Central Hospital, Department of Oncology, Helsinki, Finland, 4Helsinki University Central Hospital, Division of Infectious Diseases, Department of Medicine, Helsinki, Finland, 5Helsinki University Central Hospital, Division of Diabetes, Department of Medicine, Helsinki, Finland

Objectives: No pharmacological treatment is effective for HAART-associated lipoatrophy (HAL). In vitro, uridine abrogates NRTI-induced mitochondrial toxicity on adipocytes. Methods: 20 patients with HAL under stavudine- or zidovudine-containing HAART were randomized to receive either NucleomaxX, a dietary supplement which increases uridine serum levels (36 grams NucleomaxX TID for 10 days/month) or placebo for 3 months. Body composition was measured using DEXA and MRI. Liver fat was quantified by proton spectroscopy. Results: 18 patients completed the study. No virological failure was observed. 1 patient discontinued NucleomaxX due to taste and one patient died of myocardial infarction in the placebo group. There were no significant differences between the groups at baseline.   Uridine Baseline Uridin 3 months Placebo baseline Placebo 3 months Body mass index (kg/m2) 24.7 ± 1.2 25.1 ± 1.3 * 22.2 ± 1.0 22.4 ± 0.9 Total limb fat (g) 3370 ± 890 4260 ± 940 * # 3110 ± 900 3340 ± 880 Visceral fat (cm3) 2320 ± 320 2520 ± 370 * # 2030 ± 500 1940 ± 460 Liver fat (%) 6.4 ± 3.1 7.7 ± 3.9 12.8 ± 5.2 8.7 ± 3.1 S-Insulin (mU/l) 13.0 ± 4.1 13.7 ± 5.7 10.0 ± 2.3 9.3 ± 2.4 S-Triglycerides (mmol/l) 2.8 ± 0.5 3.0 ± 0.4 3.5 ± 0.9 3.0 ± 0.9 Plasma lactate (mmol/l) 1.5 ± 0.2 1.3 ± 0.1 1.5 ± 0.2 1.4 ± 0.1 Venous blood pH 7.33 ± 0.01 7.36 ± 0.01 * 7.34 ± 0.01 7.35 ± 0.01 Venous blood base excess -0.2 ± 0.3 1.1 ± 0.3 * 0.0 ± 0.6 0.1 ± 0.3 *p<0.05 for change between baseline and 3 months within each study group. # p<0.05 for change between uridine and placebo groups. Data are mean ± SEM. Conclusion: Uridine increased the amount of subcutaneous and visceral fat, and also increased blood pH and base excess in lipoatrophic patients with unchanged HAART, but did not change liver fat content or markers of insulin resistance. Contact: Jussi Sutinen, Helsinki University Central Hospital, Division of Infectious Diseases and Diabetes, Department of Medicine, P.O.Box 348, 00029 Helsinki HUS, Finland, Email: jussi.sutinen@hus.fi