Mitochondrial function, inflammation, fat and bone in HIV lipoatrophy: randomized study of uridine supplementation or switch to tenofovir
Language: 
English
Short Title: 
Mitochondrial function, inflammation, fat and bone in HIV lipoatrophy
Abstract: 

BACKGROUND: Lipoatrophy modestly improves when the thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI) is removed. In vitro, uridine (NucleomaxX(®); Pharma Nord, Vojens, Denmark) reversed tNRTI mitochondrial toxicity. METHODS: All patients had lipoatrophy on a tNRTI-containing regimen with HIV RNA<400 copies/ml. A randomized 48-week study switched patients from tNRTI to tenofovir (TDF) or added uridine (continuing tNRTI). End points were changes in limb fat (DEXA), subcutaneous abdominal fat mitochondrial DNA (mtDNA) and mitochondrial RNA (mtRNA), inflammation markers (soluble tumour necrosis factor receptors, high-sensitivity C reactive protein [hsCRP], interleukin-6 [IL-6], soluble vascular cell adhesion molecule 1), bone mineral density (BMD) of the hip and spine, HIV-1 RNA, CD4(+) T-cells and fasting metabolic parameters. RESULTS: Fifty patients were enrolled (n=24 TDF switch; n=26 uridine); median age 48 years; 54% white; 86% male; limb fat 4,494 g. Baseline characteristics were similar between groups. In the NucleomaxX(®) arm, mtRNA increased (all P<0.001), hsCRP and IL-6 increased (both P=0.02), whereas fat mtDNA decreased without changes in limb fat. In the TDF-switch arm, fat mtDNA and inflammation markers did not change; however, significant increases in mtRNAs (P<0.001), limb fat (409 g; IQR -59-1,155) and CD4(+) T-cell count (P=0.03), and decreases in total and hip BMD (median -3.3%; IQR -5.1-0; P=0.005) were observed. Between-group changes were significant for fat mtDNA, hsCRP, IL-6, limb fat and hip BMD. No correlation was found between changes in limb fat and those of fat mtRNA, inflammation markers or protease inhibitor duration. CONCLUSIONS: In HIV lipoatrophy, NucleomaxX(®) improved mtRNA, but worsened inflammation markers and fat mtDNA without changes in limb fat. Switching from a tNRTI to TDF for 48 weeks increased limb fat and fat mtRNA. Large decreases in total and hip BMD were seen after TDF switch.
ClinicalTrials.gov identifier: NCT00119379.

Author(s): 
McComsey, Grace A.
O'Riordan, MaryAnn
Choi, Julia
Libutti, Daniel
Rowe, David
Storer, Norma
Harrill, Danielle
Gerschenson, Mariana
Item Type: 
Journal Article
Publication Title: 
Antiviral Therapy
Journal Abbreviation: 
Antivir. Ther. (Lond.)
Publication Date: 
2012
Publication Year: 
2012
Pages: 
347-353
Volume: 
17
Issue: 
2
ISSN: 
2040-2058
DOI: 
10.3851/IMP1928
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 22293126 PMCID: PMC3302940

Turabian/Chicago Citation

Grace A. McComsey, MaryAnn O'Riordan, Julia Choi, Daniel Libutti, David Rowe, Norma Storer, Danielle Harrill and Mariana Gerschenson. 2012. "Mitochondrial function, inflammation, fat and bone in HIV lipoatrophy: randomized study of uridine supplementation or switch to tenofovir." Antiviral Therapy 17: 2: 347-353. 10.3851/IMP1928.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.3851/IMP1928 | issn = 2040-2058 | volume = 17 | pages = 347-353 | last = McComsey | first = Grace A. | coauthors = O'Riordan, MaryAnn, Choi, Julia, Libutti, Daniel, Rowe, David, Storer, Norma, Harrill, Danielle, Gerschenson, Mariana | title = Mitochondrial function, inflammation, fat and bone in HIV lipoatrophy: randomized study of uridine supplementation or switch to tenofovir | journal = Antiviral Therapy | date = 2012 | pmid = | pmc = }} </ref>