Purine and Pyrimidine Metabolism in Hereditary Oroticaciduria During a 15 Year Follow-Up Study

Webster, D. R.; Simmonds, H. Anne; Potter, Christine; Becroft, D. M. O.

doi:10.1007/978-1-4684-8559-2_34

Cited by 5 publications

(2 citation statements)

References 6 publications

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“…Although the safety profile of oral uridine or its prodrugs was reported to be excellent in HIV-negative subjects (20–21), it is important to rule out a negative effect of uridine or its metabolites on the ability of antiretroviral nucleoside analogues to inhibit HIV reverse transcriptase. While such an effect was previously excluded for a number of NRTIs and their combinations in phenotypic HIV-resistance assays and for zidovudine in an animal model (13–15), only small studies have been conducted in HIV-infected subjects (9–10).…”

Section: Discussionmentioning

confidence: 99%

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

McComsey

Walker

Budhathoki

et al. 2010

Aids

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BACKGROUND Lipoatrophy is prevalent on thymidine NRTIs (tNRTI). 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-gram difference between arms at week-48. A stratified Wilcoxon rank-sum test was used to assess between-arm differences. RESULTS The 165 subjects were 91% male, 62% white; median age 49 years, CD4 506 cells/mm3, and limb fat 3037 grams; 81% had HIV-1 RNA ≤50 copies/mL; 76% were on AZT. Baseline characteristics were similar between groups. Only 59% completed 48-weeks of treatment, however only 3 subjects (1 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 subjects with ≥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, 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 safe and did not impair virologic control.

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Section: Discussionmentioning

confidence: 99%

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

McComsey

Walker

Budhathoki

et al. 2010

Aids

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“…Although the safety profile of oral uridine or its prodrugs was reportedly excellent in HIVnegative subjects (Webster et al, 1979;Manis et al, 1997), it is important to rule out a negative effect of uridine or its metabolites on the ability of antiretroviral nucleoside analogues to inhibit HIV reverse transcriptase. Although such effect was previously excluded for a number of NRTI and their combinations in phenotypic HIV-resistance assays and for zidovudine in an animal model (Sommadossi et al, 1988;Calabresi et al, 1990;Koch et al, 2003), studies in HIV-infected subjects are needed.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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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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The Development of Allopurinol

Rundles¹

1985

Arch Intern Med

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Purine and Pyrimidine Metabolism in Hereditary Oroticaciduria During a 15 Year Follow-Up Study

Cited by 5 publications

References 6 publications

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

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

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

The Development of Allopurinol

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