Mitochondria in the pathogenesis of lipodystrophy induced by anti-HIV antiretroviral drugs: actors or bystanders?
Effective therapies are now available that can stop the progression of HIV infection and significantly delay the onset of AIDS. The "highly active antiretroviral therapy" (HAART) is a combination of potent antiretroviral drugs such as viral protease inhibitors or nucleoside-analogue reverse-transcriptase inhibitors, that has a variety of serious side effects, including lipodystrophy, a pathology characterized by accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia, insulin resistance as well as fat wasting in face and limbs. There is still an open debate that concerns the precise responsibility of HAART as well as metabolic pathways and mechanisms that are involved in the onset of lipodystrophy. The similarities with multiple symmetric lipomatosis (MSL), in which mitochondria impairment plays a crucial role, lead to the hypothesis that drug-induced damages to mitochondrial DNA are able to alter mitochondria functionality to an extent that is similar to what occurs in MSL. In addition, several evidences indicate that HAART is also linked to a deregulated production of tumour necrosis factor-alpha, which uses mitochondria as intracellular targets. In this paper, we review data concerning the role of mitochondria in the pathogenesis of lipodystrophy, and advance a unifying hypothesis involving either direct or indirect effects of the drugs employed during HAART.
Cossarizza
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Department of Biomedical Sciences, University of Modena and Reggio Emilia School of Medicine, Modena, Italy. cossariz@unimo.it
Mussini
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Viganò
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D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D016923:Cell Death; D002470:Cell Survival; D002648:Child; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced / Q000473:pathology*; D008928:Mitochondria / Q000502:physiology*; D011110:Polymorphism, Genetic; D013577:Syndrome
D019380:Anti-HIV Agents