Uridine supplementation in the treatment of HIV lipoatrophy

Results of ACTG 5229

Grace A. McComsey, Ulrich A. Walker, Chakra B. Budhathoki, Zhaohui Su, Judith S. Currier, Lisa Kosmiski, Linda G. Naini, Stéphannie Charles, Kathy Medvik, Judith A. Aberg

Research output: Contribution to journalArticle

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 3037g;81% had HIV-1 RNA 50copies/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.

Original languageEnglish (US)
Pages (from-to)2507-2515
Number of pages9
JournalAIDS
Volume24
Issue number16
DOIs
StatePublished - Oct 23 2010
Externally publishedYes

Fingerprint

Uridine
Extremities
Fats
HIV
Reverse Transcriptase Inhibitors
Nucleosides
Thymidine
CD4 Lymphocyte Count
Nonparametric Statistics
Arm
Therapeutics
Placebos
RNA
Zidovudine
Adipocytes
Sample Size
Multicenter Studies
HIV-1
Diarrhea
Fasting

Keywords

  • HIV
  • Lipoatrophy
  • Lipodystrophy
  • Mitochondrial toxicity
  • Uridine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

McComsey, G. A., Walker, U. A., Budhathoki, C. B., Su, Z., Currier, J. S., Kosmiski, L., ... Aberg, J. A. (2010). Uridine supplementation in the treatment of HIV lipoatrophy: Results of ACTG 5229. AIDS, 24(16), 2507-2515. https://doi.org/10.1097/QAD.0b013e32833ea9bc

Uridine supplementation in the treatment of HIV lipoatrophy : Results of ACTG 5229. / McComsey, Grace A.; Walker, Ulrich A.; Budhathoki, Chakra B.; Su, Zhaohui; Currier, Judith S.; Kosmiski, Lisa; Naini, Linda G.; Charles, Stéphannie; Medvik, Kathy; Aberg, Judith A.

In: AIDS, Vol. 24, No. 16, 23.10.2010, p. 2507-2515.

Research output: Contribution to journalArticle

McComsey, GA, Walker, UA, Budhathoki, CB, Su, Z, Currier, JS, Kosmiski, L, Naini, LG, Charles, S, Medvik, K & Aberg, JA 2010, 'Uridine supplementation in the treatment of HIV lipoatrophy: Results of ACTG 5229', AIDS, vol. 24, no. 16, pp. 2507-2515. https://doi.org/10.1097/QAD.0b013e32833ea9bc
McComsey, Grace A. ; Walker, Ulrich A. ; Budhathoki, Chakra B. ; Su, Zhaohui ; Currier, Judith S. ; Kosmiski, Lisa ; Naini, Linda G. ; Charles, Stéphannie ; Medvik, Kathy ; Aberg, Judith A. / Uridine supplementation in the treatment of HIV lipoatrophy : Results of ACTG 5229. In: AIDS. 2010 ; Vol. 24, No. 16. pp. 2507-2515.
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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 3037g;81{\%} had HIV-1 RNA 50copies/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.",
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