Uridine supplementation for the treatment of antiretroviral therapy-associated lipoatrophy: a randomized, double-blind, placebo-controlled trial.
BACKGROUND
Highly active antiretroviral therapy (HAART) is associated with loss of subcutaneous fat (lipoatrophy) presumably due to mitochondrial toxicity of nucleoside reverse transcriptase inhibitors. In vitro, uridine abrogates thymidine analogue-induced toxicity in adipocytes.


METHODS
A total of 20 patients with HAART-associated lipoatrophy were randomized to receive either a dietary uridine supplement (36 g three times a day for 10 consecutive days/month) or placebo, for 3 months. Body composition was measured using dual energy X-ray absorptiometry, magnetic resonance imaging and proton spectroscopy. Data are mean +/- standard error of mean.


RESULTS
The mean increases in limb fat (880 +/- 140 versus 230 +/- 270 g; P < 0.05), intra-abdominal fat (210 +/- 80 versus -80 +/- 70 cm3; P < 0.05) and total body fat (1920 +/- 240 versus 240 +/- 520 g; P < 0.01) were significantly greater in the uridine than in the placebo group. Within the uridine group, the changes from baseline to 3 months were statistically significant in total limb fat (P < 0.001), intra-abdominal fat (P < 0.05) and total body fat (P < 0.001). The proportion of limb fat to total fat increased from 18% to 25% (P < 0.05) in the uridine group. Liver fat content and lean body mass remained unchanged in both groups. High-density lipoprotein-cholesterol concentrations decreased in the uridine and increased in the placebo group, whereas fasting serum insulin concentrations did not change. Uridine supplementation was well tolerated and the virological effect of HAART was not affected.


CONCLUSIONS
Uridine supplementation significantly and predominantly increased subcutaneous fat mass in lipoatrophic HIV-infected patients during unchanged HAART.
Sutinen
Jussi
J
Division of Diabetes, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Walker
Ulrich A
UA
Sevastianova
Ksenia
K
Klinker
Hartwig
H
Häkkinen
Anna-Maija
AM
Ristola
Matti
M
Yki-Järvinen
Hannele
H
D015502:Absorptiometry, Photon; D000284:Administration, Oral; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001823:Body Composition / Q000187:drug effects; D050218:Body Fat Distribution; D019587:Dietary Supplements; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D013057:Spectrum Analysis; D050151:Subcutaneous Fat / Q000187:drug effects; D016896:Treatment Outcome; D014529:Uridine / Q000008:administration & dosage / Q000627:therapeutic use*
D044966:Anti-Retroviral Agents; D014529:Uridine