The Influence of HIV Infection and Antiretroviral Therapy on the Mitochondrial Membrane Potential of Peripheral Mononuclear Cells

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 (ΔΨ_m) is the most direct measure of the state of energization of the mitochondria. We analysed ΔΨ_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 ΔΨ_m of PBMC was measured by flow cytometry using the dye JC-1.

Results

The ΔΨ_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 ΔΨ_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 ΔΨ_m increased significantly in therapy-naive patients after starting ART (P=0.001). Patients with lipoatrophy had significantly lower ΔΨ_m than patients without lipodystrophy or with lipohypertrophy (P=0.023).

Conclusions

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