Anti-HIV drugs and the mitochondria.
Several drugs are currently used that can significantly prolong the course of the infection with the human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). Among these drugs, the nucleosidic inhibitors of viral reverse transcriptase can alter mitochondrial (mt) function by inhibiting the mitochondrial DNA polymerase gamma (the enzyme responsible for the replication of mtDNA). Decreased mtDNA content provokes a diminished synthesis of respiratory chain enzymes, leading to alterations in mt function. These are in turn responsible for a variety of side effects frequently observed in HIV+ patients, that range from hyperlactatemia and lactic acidosis to lipodystrophy, a pathology characterized by accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia, insulin resistance and fat wasting in face and limbs. In this paper, data concerning the effects of different compounds on mitochondria, their role in the pathogenesis of lipodystrophy, and problems related to studies on the mt toxicity of antiviral drugs are reviewed and thoroughly discussed.
Pinti
Marcello
M
Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia School of Medicine, via Campi 287, 41100 Modena, Italy.
Salomoni
Paolo
P
Cossarizza
Andrea
A
D000140:Acidosis, Lactic / Q000139:chemically induced; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D008060:Lipodystrophy / Q000139:chemically induced; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D028361:Mitochondrial Diseases / Q000139:chemically induced*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors