The influence of HIV infection and antiretroviral therapy on the mitochondrial membrane potential of peripheral mononuclear cells.
OBJECTIVE
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.
Sternfeld
Thomas
T
Department of Infectious Diseases, Medizinische Poliklinik, University of Munich, Germany. thomas.sternfeld@lrz.tum.de
Schmid
Mathias
M
Tischleder
Annette
A
Mudra
Susanne
S
Schlamp
Angelika
A
Kost
Bernd P
BP
Gruber
Rudolf
R
Youle
Mike
M
Bogner
Johannes R
JR
Goebel
Frank-Detlef
FD
D000140:Acidosis, Lactic / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000821:virology; D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000821:virology; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000821:virology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000821:virology; D028361:Mitochondrial Diseases / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000821:virology; D011446:Prospective Studies; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents