Uridine supplementation in the treatment of HIV lipoatrophy: results of ACTG 5229.

TitleUridine supplementation in the treatment of HIV lipoatrophy: results of ACTG 5229.
Publication TypeJournal Article
Year of Publication2010
AuthorsMcComsey GA, Walker UA, Budhathoki CB, Su Z, Currier JS, Kosmiski L, Naini LG, Charles S, Medvik K, Aberg JA
Corporate AuthorsAIDS Clinical Trials Group A5229 Team
JournalAIDS
Volume24
Issue16
Pagination2507-15
Date Published2010 Oct 23
ISSN1473-5571
KeywordsAdult, CD4 Lymphocyte Count, Double-Blind Method, Female, HIV Infections, HIV-1, HIV-Associated Lipodystrophy Syndrome, Humans, Male, Medication Adherence, Pilot Projects, Quality of Life, Uridine, Viral Load
Abstract

BACKGROUND: Lipoatrophy is prevalent on thymidine nucleoside reverse transcriptase inhibitors (tNRTIs). A pilot trial showed that uridine (NucleomaxX) increased limb fat.

METHODS: A5229 was a multicenter trial in which HIV-infected individuals with lipoatrophy on tNRTI regimens were randomized to NucleomaxX or placebo. Primary endpoint was change in limb fat from baseline to week 48. The study was powered to detect 400-g difference between arms at week 48. A stratified Wilcoxon rank-sum test was used to assess between-arm differences.

RESULTS: The 165 participants were 91% men, 62% white; median age 49 years, CD4 cell count 506 cells/μl, and limb fat 3037 g; 81% had HIV-1 RNA 50 copies/ml or less; 76% were on zidovudine (ZDV). Baseline characteristics were similar between groups. Only 59% completed 48 weeks of treatment; however, only three participants (one on uridine) discontinued due to toxicity (diarrhea). In intent to treat, there was no difference for changes in limb fat between treatments at week 24 or week 48. On as-treated analysis, uridine resulted in an increase in %limb fat vs. placebo (3.4 vs. -0.8%, P = 0.01) at week 24 but not at week 48 (1.8 vs. 3.8%, P = 0.93). Similar results were seen when limiting the analysis to patients with at least 80% adherence. The results were not related to severity of lipoatrophy or type of tNRTI. No changes were found in facial anthropometrics, fasting lipids, trunk fat, CD4 cell count, or HIV RNA.

CONCLUSIONS: We found a modest transient improvement in limb fat after 24 weeks of uridine. The lack of sustained efficacy at week 48 was not due to changes in adherence or reduction in sample size. Uridine was well tolerated and did not impair virologic control.

DOI10.1097/QAD.0b013e32833ea9bc
Alternate JournalAIDS
PubMed ID20827170
PubMed Central IDPMC2956768
Grant List1 UO1 AI 069494-01 / AI / NIAID NIH HHS / United States
5 U0I AI069415-03 / AI / NIAID NIH HHS / United States
5-MO1 RR00044 / RR / NCRR NIH HHS / United States
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RR-00037 / RR / NCRR NIH HHS / United States
RR00095 / RR / NCRR NIH HHS / United States
RR024996 / RR / NCRR NIH HHS / United States
RR025780 / RR / NCRR NIH HHS / United States
U01 A106942 / / PHS HHS / United States
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U01AI069511-02 / AI / NIAID NIH HHS / United States
U01AI69418-01 / AI / NIAID NIH HHS / United States
U54-RR023561 / RR / NCRR NIH HHS / United States
UL1 RR-025014 / RR / NCRR NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States