The influence of HIV infection and antiretroviral therapy on the mitochondrial membrane potential of peripheral mononuclear cells

Antivir Ther. 2007;12(5):769-78.

Abstract

Objectives: Clinical disorders occurring in HIV-infected patients on antiretroviral therapy (ART) have been linked to mitochondrial dysfunction, for example, lactic acidosis and lipodystrophy. Mitochondrial membrane potential (delta psi m) is the most direct measure of the state of energization of the mitochondria. We analysed delta psi m, of peripheral blood mononuclear cells (PBMCs) in HIV-negative, healthy subjects (n=8), HIV-infected, treatment-naive patients (n=30), and HIV-infected patients on ART (n=58). The influence of ART was analysed in six patients who started their first regimen.

Methods: The delta psi m of PBMC was measured by flow cytometry using the dye JC-1.

Results: The delta psi m was significantly lower in HIV-infected patients than in HIV-negative controls. This difference was detected in both treated (P = 0.0001) and untreated patients (P = 0.001). The delta psi m of PBMCs was highly correlated with CD4+ T-cell count in therapy-naive patients (P = 0.002, r = 0.546) and in treated patients (P = 0.028, r = 0.288). The delta psi m increased significantly in therapy-naive patients after starting ART (P = 0.001). Patients with lipoatrophy had significantly lower delta psi m than patients without lipodystrophy or with lipohypertrophy (P = 0.023).

Conclusions: In HIV-infected persons delta psi m is significantly reduced. Patients with lipoatrophy have significantly reduced delta psi m. This is the first study showing that the delta psi m of PBMCs is highly correlated with CD4+ T-cell count in HIV infection.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Acidosis, Lactic / blood
  • Acidosis, Lactic / chemically induced
  • Acidosis, Lactic / immunology
  • Acidosis, Lactic / virology
  • Adult
  • Anti-Retroviral Agents / adverse effects
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / adverse effects
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / virology
  • Cross-Sectional Studies
  • Fatty Liver / blood
  • Fatty Liver / chemically induced
  • Fatty Liver / immunology
  • Fatty Liver / virology
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-Associated Lipodystrophy Syndrome / blood
  • HIV-Associated Lipodystrophy Syndrome / chemically induced
  • HIV-Associated Lipodystrophy Syndrome / immunology
  • HIV-Associated Lipodystrophy Syndrome / virology
  • Humans
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / virology
  • Male
  • Membrane Potential, Mitochondrial / drug effects*
  • Middle Aged
  • Mitochondria / drug effects*
  • Mitochondria / virology
  • Mitochondrial Diseases / blood
  • Mitochondrial Diseases / chemically induced*
  • Mitochondrial Diseases / immunology
  • Mitochondrial Diseases / virology
  • Prospective Studies
  • Reproducibility of Results
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-Retroviral Agents