Exposure to dideoxynucleosides is reflected in lowered mitochondrial DNA in subcutaneous fat

Catherine L. Cherry, Michelle E. Gahan, Justin C. McArthur, Sharon R. Lewin, Jennifer F. Hoy, Steven L. Wesselingh

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112 Citations (Scopus)

Abstract

Objectives: Nucleoside reverse transcriptase inhibitors (NRTIs), particularly dideoxynucleoside analogs (ddNs), used in the treatment of HIV, inhibit mitochondrial DNA polymerase γ in vitro. Mitochondrial DNA (mtDNA) depletion is proposed as the underlying mechanism of many of the in vivo side effects of these agents. A reliable and valid laboratory test to detect this is not yet available. The objective of this study was to correlate tissue mtDNA quantification in HIV-infected patients with exposure to nucleoside analogs. Methods: 60 HIV-infected adults underwent detailed clinical assessment and blood and tissue sampling. Clinical and antiretroviral treatment details were correlated with results of plasma lactate assays, and real-time polymerase chain reaction quantification of mtDNA in peripheral blood mononuclear cells (PBMCs) and subcutaneous fat from the lower limb. Results: Forty-nine (82%) subjects were on combination antiretroviral therapy. Of these, 33 (55%) were currently receiving one or more ddNs (stavudine, didanosine, or zalcitabine). mtDNA in subcutaneous fat was lower in subjects currently on ddNs than in those not taking ddNs (mean [log10] 2.47 vs. 2.74, p = .002). Plasma lactate was somewhat higher in subjects currently taking ddNs than those on no antiretroviral treatment (median 1.5 vs. 1.0, p = .03), but was not significantly different in either of these groups compared with subjects on other NRTIs. mtDNA in PBMCs did not vary with treatment status. Conclusions: mtDNA in subcutaneous fat was significantly reduced in patients currently taking ddNs. mtDNA in PBMCs was independent of patient exposure to NRTIs.

LanguageEnglish
Pages271-277
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume30
Issue number3
DOIs
Publication statusPublished - 1 Jul 2002

Keywords

  • Dideoxynucleosides
  • HIV
  • Lactate
  • Mitochondrial DNA

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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