Analysis of the mitochondrial DNA genome in the peripheral blood leukocytes of HIV-infected patients with or without lipoatrophy.
OBJECTIVE
To investigate the molecular mechanisms of nucleoside analogue reverse transcriptase inhibitor (NRTI)-associated mitochondrial dysfunction.


METHODS
Peripheral blood samples were collected from 10 healthy individuals, 10 HIV-infected, NRTI-treated patients with lipoatrophy, and four HIV-infected patients naive to all antiretrovirals. DNA was isolated from the leukocytes and the mitochondrial genome analyzed for DNA depletion, deletions and point mutations.


RESULTS
We were not able to detect mitochodrial DNA (mtDNA) depletion, deletions, or DNA rearrangements in any of the specimens, including one from a patient with fulminant lactic acidosis. A complete analysis of the entire mitochondrial genome by temporal temperature gradient gel electrophoresis revealed several nucleotide substitutions in blood mtDNA of several HIV infected patients.


CONCLUSIONS
We found no evidence for NRTI-associated mtDNA depletion or gross mtDNA mutations in leukocytes of HIV-infected patients, regardless of their treatment history. Thus, either NRTI-induced mutations in mtDNA are tissue-specific or alternatively, pre-existent mtDNA variations in HIV disease predispose to the development of clinically apparent mitochondrial dysfunction during NRTI therapy. The significance of mtDNA variations in the development of mitochondrial-related clinical conditions in HIV patients with or without NRTI therapy is to be further investigated.
McComsey
Grace
G
Department of Pediatrics, Division of Infectious Diseases, Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA. mccomsey.grace@clevelandactu.org
Tan
Duan-Jun
DJ
Lederman
Michael
M
Wilson
Elizabeth
E
Wong
Lee-Jun
LJ
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D019247:HIV Wasting Syndrome / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors