Cardiomyopathy, nucleoside reverse transcriptase inhibitors and mitochondria are linked through AIDS and its therapy.
Nucleoside reverse transcriptase inhibitors (NRTIs) in highly active antiretroviral therapy (HAART) bring serious side effects to light. Mitochondrial dysfunction, mtDNA replication defects and mtDNA depletion in target tissues are observed experimentally and clinical confirmation is present in some cases. Organ-specific pathological changes, particularly in the cardiovascular system, result from and are frequently attributed to HAART where NRTIs are included. Mechanisms of mitochondrial toxicity are incompletely understood, but could reasonably relate to inhibition of DNA polymerase-gamma (the enzyme responsible for mtDNA replication in eukaryotes) by pharmacologically active NRTI triphosphates. Cellular and biological implications of the pharmacologic events are addressed.
Lewis
William
W
Department of Pathology, Emory University, 101 Woodruff Circle, WMB, Room 7117, Atlanta, GA 30322, USA. wlewis@emory.edu