Uridine Supplementation for the treatment of Antiretroviral Therapy-Associated Lipoatrophy: A Randomized, Double-Blind, Placebo-Controlled Trial
What this study found
Uridine increased limb fat mass by 880 g vs 230 g in placebo (P<0.05), intra-abdominal fat by 210 cm3 vs -80 cm3 (P<0.05), and total body fat by 1,920 g vs 240 g (P<0.01) after 3 months. Limb fat as a proportion of total fat rose from 18% to 25% (P<0.05). Lean mass and liver fat did not change; HDL cholesterol decreased in the uridine group, while insulin resistance and HbA1c remained unchanged. HIV-1 viral load stayed suppressed in participants with baseline <50 copies/mL; the regimen was generally well tolerated with one dropout due to taste and one placebo death from myocardial…
- Study & population
- Randomized, double-blind, placebo-controlled trial in HIV-1-infected adults with HAART-associated lipodystrophy; 20 participants (10 per group) on stable HAART for ≥18 months; age >18; 9 men/1 woman in the uridine group and 8 men/2 women in the placebo group; most had HIV-1 RNA <50 copies/mL at baseline; some on stavudine (d4T) or zidovudine (AZT);…
- Intervention
- Uridine supplementation (NucleomaxX), 36 g per dose, taken orally three times daily for 10 consecutive days each month, for 3 months (10 days on, 20 days off).
- Key limitation
- Small sample size (n=20; 18 completed), short duration (3 months), single-center; one dropout due to taste and one death; limited safety data for longer use; generalizability to other ART regimens or patients unable to switch thymidine analogues uncertain; observed increase in intra-abdominal fat warrants caution.
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Open PDFOriginal abstract
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 (1,920 ±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. Conclusion Uridine supplementation significantly and predominantly increased subcutaneous fat mass in lipoatrophic HIV-infected patients during unchanged HAART.