Mitochondrial toxicity of NRTI antiviral drugs: an integrated cellular perspective.
Highly active antiretroviral therapy (HAART) regimes based on nucleoside reverse transcriptase inhibitors (NRTIs) have revolutionized the treatment of AIDS in recent years. Although HAART can successfully suppress viral replication in the long term, it is not without significant toxicity, which can seriously compromise treatment effectiveness. A major toxicity that has been recognized for more than a decade is NRTI-related mitochondrial toxicity, which manifests as serious side effects such as hepatic failure and lactic acidosis. However, a lack of understanding of the mechanisms underlying mitochondrial toxicity has hampered efforts to develop novel drugs with better side-effect profiles. This review characterizes the pharmacological mechanisms and pathways that are involved in mitochondrial dysfunction caused by NRTIs, and suggests opportunities for future pharmacological research.
Lewis
William
W
Emory University, Department of Pathology, 1639 Pierce Drive, Room 7117, Atlanta, Georgia 30322, USA.
Day
Brian J
BJ
Copeland
William C
WC
D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008930:Mitochondria, Liver / Q000187:drug effects*; D008969:Molecular Sequence Data; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid
D018894:Reverse Transcriptase Inhibitors