Mitochondrial DNA assessment in adipocytes and peripheral blood mononuclear cells of HIV-infected patients with lipodystrophy according to a validated case definition.
BACKGROUND
Several studies have compared mitochondrial DNA (mtDNA) content in tissue from HIV-1-infected patients on highly active antiretroviral therapy with and without evidence of lipodystrophy, the diagnosis of which was based on subjective clinical assessment.


OBJECTIVE
The aim of this study was to assess the utility of mtDNA quantification as a marker of HIV-associated lipodystrophy as diagnosed using a published validated case definition.


METHODS
We assessed mtDNA content in adipocytes from both thigh and lumbar subcutaneous adipose tissue (n=19), and in peripheral blood mononuclear cells (PBMC) (n=26), obtained from 26 HIV-1-infected patients classified as having lipodystrophy (n=17) or not having lipodystrophy (n=9) according to the validated definition derived from the Lipodystrophy Case Definition Study.


RESULTS
The adipocyte and PBMC mtDNA contents did not significantly differ between patients with and without lipodystrophy. Lipodystrophy patients had been treated for significantly longer times, especially with dideoxynucleoside analogues. In both groups, the thigh adipocyte mtDNA content was significantly greater than that of the lumbar region. When all patients were considered together, a statistically significant negative correlation was found between thigh adipocyte mtDNA content and stavudine treatment duration.


CONCLUSIONS
Longer exposure to dideoxynucleoside analogues was associated with lipodystrophy, and longer exposure to stavudine was correlated with lower mtDNA content in thigh adipocytes. However, a single measurement of adipocyte mtDNA content in this limited sample of patients could not distinguish between patients with and without clinical lipodystrophy. The observed variation in mtDNA content between different subcutaneous adipose tissue depots argues for harmonization of future studies regarding which depot to biopsy.
Casula
M
M
International Antiviral Therapy Evaluation Centre, Pietersbergweg 8, 1105 BM Amsterdam, The Netherlands. m.casula@iatec.com
van der Valk
M
M
Wit
F W
FW
Nievaard
M A
MA
Reiss
P
P
D017667:Adipocytes / Q000737:chemistry*; D000273:Adipose Tissue / Q000737:chemistry*; D000328:Adult; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000097:blood; D015224:Dideoxynucleosides / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1 / Q000235:genetics*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000175:diagnosis*; D006801:Humans; D008161:Lumbosacral Region; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D013848:Thigh
D004272:DNA, Mitochondrial; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine