Mitochondrial dysfunction in CD4+lymphocytes from stavudine-treated HIV patients

Lloyd Einsiedel, Catherine L. Cherry, Freya L. Sheeran, Anna Friedhuber, Steve L. Wesselingh, Salvatore Pepe

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11 Citations (Scopus)


HIV therapy with nucleoside analogue reverse transcriptase inhibitors (NRTI) such as stavudine remains in widespread use in resource-limited nations due to potent efficacy, convenience of formulation and lack of practical alternatives. However, it remains unclear whether adverse side effects with NRTI include reduced mitochondrial respiratory function, particularly in peripheral blood lymphocytes (PBLs). The aim of this study was to determine whether stavudine-based highly active antiretroviral therapy (HAART) is associated with impaired mitochondrial respiratory transport chain function in patient derived CD4. +. PBLs. CD4. +. PBLs were isolated from asymptomatic HIV-infected patients treated with stavudine-HAART for 3. months (n= 10), HIV-infected patients not on treatment (n= 9) and uninfected controls (n= 18). The basal mitochondrial oxygen consumption of CD4. +. PBLs from stavudine-treated patients was reduced relative to that of untreated HIV-infected patients and controls (stavudine treated group, 4.22 (25% 2.16, 75% 8.84); control uninfected, 11.2 (25% 3.95, 75% 16.6); untreated 18.1 (25% 11.8, 75% 37.9). ng oxygen atoms/min/ml). Maximal oxygen consumption (stimulated with the proton ionophore FCCP) in cells from stavudine treated patients was also reduced relative to that of untreated patients and controls (stavudine treated, 24.4 ± 10.5; control uninfected, 50.6 ± 39.5; untreated, 68.8 ± 41.1. ng oxygen atoms/min/ml). Citrate synthase activities, relative mitochondrial volume (by electron microscopy) and mtDNA copy numbers per cell were not different between groups. Therapy with stavudine results in impaired mitochondrial function in CD4. +. PBLs that does not appear to be due to reduced mitochondrial volume or DNA content and cannot be attributed to infection with HIV.

Original languageEnglish
Pages (from-to)534-539
Number of pages6
Issue number5
Publication statusPublished or Issued - Aug 2010
Externally publishedYes


  • CD4+
  • HIV
  • Lymphocyte
  • Mitochondria
  • Nucleoside analogue reverse transcriptase inhibitors
  • Oxygen consumption

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology

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