Mitochondrial DNA levels in fat and blood cells from patients with lipodystrophy or peripheral neuropathy and the effect of 90 days of high-dose coenzyme Q treatment: a randomized, double-blind, placebo-controlled pilot study.
BACKGROUND
Mitochondrial toxicity can be induced by reverse-transcriptase inhibitors, and an association between levels of mitochondrial DNA (mtDNA) per cell and lipodystrophy, peripheral neuropathy, and HIV infection per se has been suggested. Studies aimed at increasing the oxidative capacity in HIV-infected patients have been sparse.


METHODS
Levels of mtDNA in fat and peripheral blood mononuclear cells (PBMCs) from 25 HIV infected patients and 10 healthy control subjects were studied with real-time PCR analysis. A placebo-controlled and double-blind design was used to assign individuals to receive either 100 mg of coenzyme Q twice daily for 3 months or a matching placebo regimen. Levels of mtDNA and other parameters were assessed before and after the intervention period.


RESULTS
The mean number of mtDNA copies per cell was lower in fat tissue obtained from patients with peripheral neuropathy (1547 mtDNA copies/cell; P=.045), patients with lipodystrophy (1732 mtDNA copies/cell; P=.003) and in HIV patients with no complications associated with highly active antiretroviral therapy (2935 mtDNA copies/cell; P=.078), compared with healthy control subjects (6198 mtDNA copies/cell). No clear difference was seen in mtDNA content in PBMCs. Coenzyme Q therapy improved the general condition of patients (P=.005) and caused a reversible increase in peripheral neuropathy pain (P=.048). Compared with placebo, treatment with coenzyme Q did not result in changes in mtDNA levels in fat cells or in PBMCs after the treatment period.


CONCLUSIONS
Levels of mtDNA in fat tissue, but not in PBMCs, were associated with peripheral neuropathy and lipodystrophy. High-dose coenzyme Q therapy increased well-being in asymptomatic HIV-infected patients and those with lipodystrophy, as well as in control subjects, but aggravated pain in patients with peripheral neuropathy.
Rabing Christensen
Eva
E
Research Unit Q, Department of Infectious Diseases, Skejby Sygehus, Aarhus University Hospital, Aarhus, Denmark. eva.rabing@studmed.au.dk
Stegger
Marc
M
Jensen-Fangel
Søren
S
Laursen
Alex Lund
AL
Ostergaard
Lars
L
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D014451:Ubiquinone / Q000009:adverse effects / Q000627:therapeutic use*
D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors; D014451:Ubiquinone