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, AIDS Clinical Trials Group A5229 Team, Michael Morgan, Brenda R Jackson, Kerriann Herbert, Megan Mendillo, Gary Matthew Cox, Martha Silberman, Christine Hurley, Roberto Corales, Valery Hughes, Todd Stroberg, Judith Silverstein Currier, Ardis Moe, David A Wininger, Laura J Laughlin, Melinda Robinson, Rebecca Creamer, Ann C Collier, Shelia Dunaway, Benigno Rodriguez, Trisha Walton, Fred R Sattler, Hannah Edmondson, Ighovwerha Ofotokun, Shannon Hebert, Carl J Fichtenbaum, Fran Hyc, Kim Whitely, Ann Marie Anderson, Eric S Daar, Mario Guerrero, Julie Hoffman, Jack Degna, Karen T Tashima, Pamela Poethke, David Currin, Susan Pedersen, Beverly Putnam, John R Koeppe, Jane Norris, Deborah Slamowitz, Allan R Tenorio, Beverly E Sha, Deborah McMahon, Carol Oriss, Amneris Luque, Mary Adams, Jorge L Santana Bagur, Olga Mendez, Ilene Wiggins, Andrea Weiss, Henry H Balfour Jr, Heather E Vezina, Manuel Revuelta, Donna Mildvan, Lorna Nagamine, Scott Souza, Michael Yin, Jolene Noel-Connor, 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, AIDS Clinical Trials Group A5229 Team, Michael Morgan, Brenda R Jackson, Kerriann Herbert, Megan Mendillo, Gary Matthew Cox, Martha Silberman, Christine Hurley, Roberto Corales, Valery Hughes, Todd Stroberg, Judith Silverstein Currier, Ardis Moe, David A Wininger, Laura J Laughlin, Melinda Robinson, Rebecca Creamer, Ann C Collier, Shelia Dunaway, Benigno Rodriguez, Trisha Walton, Fred R Sattler, Hannah Edmondson, Ighovwerha Ofotokun, Shannon Hebert, Carl J Fichtenbaum, Fran Hyc, Kim Whitely, Ann Marie Anderson, Eric S Daar, Mario Guerrero, Julie Hoffman, Jack Degna, Karen T Tashima, Pamela Poethke, David Currin, Susan Pedersen, Beverly Putnam, John R Koeppe, Jane Norris, Deborah Slamowitz, Allan R Tenorio, Beverly E Sha, Deborah McMahon, Carol Oriss, Amneris Luque, Mary Adams, Jorge L Santana Bagur, Olga Mendez, Ilene Wiggins, Andrea Weiss, Henry H Balfour Jr, Heather E Vezina, Manuel Revuelta, Donna Mildvan, Lorna Nagamine, Scott Souza, Michael Yin, Jolene Noel-Connor
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.
Conflict of interest statement
Potential conflicts: Grace A McComsey has served as a scientific advisor for Bristol Myers Squibb, GlaxoSmithKline, Abbott, and Gilead Sciences, has received research grants from Bristol Myers Squibb, GlaxoSmithKline, Abbott, Merck, and Gilead Sciences, and is currently serving as the DSMB Chair for a Pfizer-sponsored study. UA Walker has applied for patents regarding to use of uridine or its precursors in lipodystrophy, serves as a consultant for the company that produces NucleomaxX®, and has received research grants from GlaxoSmithKline and Gilead Sciences. Judith Currier has received research grants from Merck and Company, Theratechnologies, Schering Plough and Tibotec. Judith Aberg has served as a scientific advisor to Abbott Laboratories, Boehringer Ingelheim Pharmaceutical, Inc, Gilead Sciences, Inc, GlaxoSmithKline, Merck & Co, Inc, Pfizer Inc, Theratechnologies Inc, Tibotec Therapeutics, and ViiV Healthcare. She has received research support from Gilead Sciences, Inc, GlaxoSmithKline, Merck & Co, Inc, Pfizer Inc, Schering-Plough Corp, Theratechnologies Inc, Tibotec Therapeutics, Virco Lab, Inc, and Wyeth. She has received honoraria from Abbott Laboratories, Bristol-Myers Squibb, and Gilead Sciences, Inc.
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Source: PubMed