Literature DB >> 17538545

Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices.

G A McComsey1, M O'Riordan, B Setzer, D Lebrecht, E Baron, U A Walker.   

Abstract

OBJECTIVES: Uridine abrogates mitochondrial toxicities of nucleoside reverse transcriptase inhibitor in adipocyte cell culture. We aim to study the effect of uridine supplementation on human adipocyte mitochondrial DNA (mtDNA) levels in subjects with human immunodeficiency (HIV) lipoatrophy.
METHODS: Sixteen patients with lipoatrophy on stavudine-containing antiretroviral therapy were enrolled, and received NucleomaxX, a dietary supplement with a high bioavailability of uridine (36 g TID every other day for 16 weeks). Patients were then followed off-uridine for another 16 weeks. Highly active antiretroviral therapy remained unchanged during the trial.
RESULTS: Fourteen patients completed the study. Two subjects dropped out before week 4 for study-unrelated reasons. No adverse events were noted throughout the study. HIV-1 RNA, CD4 counts, liver enzymes and hemoglobin remained unchanged. Body mass index, lactate, lipids, insulin and homeostasis model assessment of insulin resistance were unaltered. Fat and peripheral blood and mononuclear cell mtDNA levels did not correlate with each other and exhibited no changes throughout the study. Lipoatrophy scores by patients and physician improved significantly at weeks 16 and 32 compared to study entry.
CONCLUSION: In this pilot study, NucleomaxX was safe, well tolerated without apparent deleterious effect on HIV indices. In contrast to in vitro data, NucleomaxX did not lead to changes in fat or blood mtDNA levels.

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Year:  2007        PMID: 17538545      PMCID: PMC4105300          DOI: 10.1038/sj.ejcn.1602793

Source DB:  PubMed          Journal:  Eur J Clin Nutr        ISSN: 0954-3007            Impact factor:   4.016


  26 in total

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Authors:  Ulrich A Walker; Markus Bickel; Severine I Lütke Volksbeck; Uwe-Peter Ketelsen; Helmut Schöfer; Bernhard Setzer; Nils Venhoff; Volker Rickerts; Schlomo Staszewski
Journal:  J Acquir Immune Defic Syndr       Date:  2002-02-01       Impact factor: 3.731

2.  Mitochondrial DNA depletion and morphologic changes in adipocytes associated with nucleoside reverse transcriptase inhibitor therapy.

Authors:  David Nolan; Emma Hammond; Annalise Martin; Louise Taylor; Susan Herrmann; Elizabeth McKinnon; Cecily Metcalf; Bruce Latham; Simon Mallal
Journal:  AIDS       Date:  2003-06-13       Impact factor: 4.177

3.  Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial.

Authors:  Véronique Joly; Philippe Flandre; Vincent Meiffredy; Nicolas Leturque; Marine Harel; Jean-Pierre Aboulker; Patrick Yeni
Journal:  AIDS       Date:  2002-12-06       Impact factor: 4.177

4.  Uridine excess does not interfere with the antiretroviral efficacy of nucleoside analogue reverse transcriptase inhibitors.

Authors:  Eva C Koch; Josef Schneider; Roland Weis; Björn Penning; Ulrich A Walker
Journal:  Antivir Ther       Date:  2003-10

5.  Beneficial effects of oral uridine in mitochondrial toxicity.

Authors:  Ulrich A Walker; Peter Langmann; Nikolaus Miehle; Michael Zilly; Hartwig Klinker; Franziska Petschner
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6.  A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy.

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Authors:  R I Fox; M L Herrmann; C G Frangou; G M Wahl; R E Morris; V Strand; B J Kirschbaum
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8.  Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study.

Authors:  Allison Martin; Don E Smith; Andrew Carr; Clare Ringland; Janaki Amin; Sean Emery; Jennifer Hoy; Cassy Workman; Nicholas Doong; Judith Freund; David A Cooper
Journal:  AIDS       Date:  2004-04-30       Impact factor: 4.177

9.  Improvement in lipoatrophy associated with highly active antiretroviral therapy in human immunodeficiency virus-infected patients switched from stavudine to abacavir or zidovudine: the results of the TARHEEL study.

Authors:  Grace A McComsey; Douglas J Ward; Siegrid M Hessenthaler; Michael G Sension; Peter Shalit; J Tyler Lonergan; Robin L Fisher; Vanessa C Williams; Jaime E Hernandez
Journal:  Clin Infect Dis       Date:  2003-12-18       Impact factor: 9.079

10.  Uridine abrogates mitochondrial toxicity related to nucleoside analogue reverse transcriptase inhibitors in HepG2 cells.

Authors:  Ulrich A Walker; Nils Venhoff; Eva C Koch; Manfred Olschewski; Josef Schneider; Bernhard Setzer
Journal:  Antivir Ther       Date:  2003-10
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  6 in total

1.  LIPODYSTROPHY SYNDROME IN HIV-INFECTED CHILDREN ON HAART.

Authors:  Steve Innes; Leon Levin; Mark Cotton
Journal:  South Afr J HIV Med       Date:  2009-12       Impact factor: 2.744

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

Authors:  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
Journal:  AIDS       Date:  2010-10-23       Impact factor: 4.177

3.  Subjective clinical lipoatrophy assessment correlates with DEXA-measured limb fat.

Authors:  Marisa Tungsiripat; Mary Ann O'Riordan; Norma Storer; Danielle Harrill; Jason Ganz; Daniel Libutti; Mariana Gerschenson; Grace A McComsey
Journal:  HIV Clin Trials       Date:  2009 Sep-Oct

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Authors:  Marisa Tungsiripat; Grace McComsey
Journal:  Curr HIV/AIDS Rep       Date:  2008-05       Impact factor: 5.495

5.  New and emerging agents in the management of lipodystrophy in HIV-infected patients.

Authors:  Eric Bonnet
Journal:  HIV AIDS (Auckl)       Date:  2010-09-17

6.  Antiretroviral therapy-induced mitochondrial toxicity: potential mechanisms beyond polymerase-γ inhibition.

Authors:  S Selvaraj; M Ghebremichael; M Li; Y Foli; A Langs-Barlow; A Ogbuagu; L Barakat; E Tubridy; R Edifor; W Lam; Y-C Cheng; E Paintsil
Journal:  Clin Pharmacol Ther       Date:  2014-03-17       Impact factor: 6.875

  6 in total

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