Analysis of the mitochondrial DNA genome in the peripheral blood leukocytes of HIV-infected patients with or without lipoatrophy

AIDS. 2002 Mar 8;16(4):513-8. doi: 10.1097/00002030-200203080-00001.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use*
  • Child, Preschool
  • DNA, Mitochondrial / drug effects*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Wasting Syndrome / genetics*
  • Humans
  • Leukocytes, Mononuclear
  • Lipid Metabolism*
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / therapeutic use*


  • Anti-HIV Agents
  • DNA, Mitochondrial
  • Reverse Transcriptase Inhibitors