Selvaraj, ShanmugapriyaGhebremichael, MusieLi, MinFoli, YramLangs-Barlow, AllisonOgbuagu, AritBarakat, LydiaTubridy, ElizabethEdifor, ReginaLam, WingCheng, Yung-ChiPaintsil, Elijah2015-08-032014Selvaraj, S., M. Ghebremichael, M. Li, Y. Foli, A. Langs-Barlow, A. Ogbuagu, L. Barakat, et al. 2014. “Antiretroviral Therapy-Induced Mitochondrial Toxicity: Potential Mechanisms Beyond Polymerase-γ Inhibition.” Clinical pharmacology and therapeutics 96 (1): 110-120. doi:10.1038/clpt.2014.64. http://dx.doi.org/10.1038/clpt.2014.64.0009-9236http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820890We hypothesized that competition between NRTI-triphosphate and endogenous deoxyribonucleoside triphosphate (dNTP) may lead to depletion of dNTP pools and mitochondrial dysfunction independent of Pol-γ inhibition. We collected peripheral blood mononuclear cells from 75 adults (25 cases: HIV-infected with mitochondrial toxicity, 25 HIV-infected positive controls, and 25 HIV-negative controls). We observed statistically significant individual and group differences in ribonucleotide (RN) and deoxyribonucleotide (dRN) pools. The median RN pool was 10062 (IQR, 7090 – 12590), 4360 (IQR, 3058 –6838), and 2968 (IQR, 2538 – 4436) pmol/106 cells for negative controls, positive controls, and cases, respectively. Cases had significantly higher absolute mtDNA copy number compared to negative controls (p<0.05). Cases had significantly higher expression of Pol-γ, nucleoside transporters, cellular kinases, and ABC compared to controls. Antiretroviral therapy perturbs ribonucleotide and deoxyribonucleotide pools. Depletion of RN and dRN pools may be associated with ART-induced mitochondrial toxicity independent of Pol-γ inhibition.en-USRibonucleotidesdeoxyribonucleotidesmitochondrial toxicityhuman immunodeficiency viruspolymerase gammanucleoside transporterscellular kinasesATP-Binding Cassette proteinsJournal Article2015-08-0310.1038/clpt.2014.64