Mitochondrial effects of antiretroviral therapies in asymptomatic patients.
BACKGROUND
A decrease in the mitochondrial (mt) DNA to nuclear DNA ratio has gained acceptance as a marker of mitochondrial toxicity in treated HIV-infected patients, but the functional meaning of this alteration is unclear.


METHODS
We assessed mtDNA content, mitochondrial content and function in peripheral blood mononuclear cells (PBMCs) of consecutive asymptomatic HIV-infected patients. Patients selected had been receiving a first-line highly active antiretroviral therapy (HAART) regimen for at least 6 months, consisting of zidovudine plus lamivudine or stavudine plus didanosine plus either nelfinavir or nevirapine, or were antiretroviral-naive. The mtDNA content was assessed by quantitative real-time PCR, mitochondrial content by citrate synthase activity, enzyme activity of complexes III and IV (both partially encoded by mtDNA) of the electron transport chain by spectrophotometry, oxygen consumption by polarography, and oxidative damage in cell membranes by monitoring cis-parinaric acid fluorescence.


RESULTS
Mitochondrial content was significantly lower in all treated groups. Patients receiving stavudine plus didanosine had mtDNA depletion and a decrease in complex IV activity. However, oxygen consumption capacity and lipid peroxidation were unaffected in all groups.


CONCLUSIONS
Long-term HAART may induce mitochondrial abnormalities in PBMC mitochondria, which do not necessarily translate into functional abnormalities, at least in asymptomatic patients.
López
Sònia
S
Muscle Research Unit, Department of Internal Medicine, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain.
Miró
Oscar
O
Martínez
Esteban
E
Pedrol
Enric
E
Rodríguez-Santiago
Benjamín
B
Milinkovic
Ana
A
Soler
Anna
A
García-Viejo
Miguel A
MA
Nunes
Virginia
V
Casademont
Jordi
J
Gatell
Josep M
JM
Cardellach
Francesc
F
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D003430:Cross-Sectional Studies; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D016049:Didanosine / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D019888:Nelfinavir / Q000627:therapeutic use; D019829:Nevirapine / Q000627:therapeutic use; D016133:Polymerase Chain Reaction / Q000379:methods; D018119:Stavudine / Q000627:therapeutic use
D000998:Antiviral Agents; D017931:DNA Primers; D004272:DNA, Mitochondrial; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D019888:Nelfinavir; D016049:Didanosine