title: Aging and HIV/AIDS: pathogenetic role of therapeutic side effects.
abstract: The intersection of aging and HIV/AIDS is a looming 'epidemic within an epidemic.' This paper reviews how HIV/AIDS and its therapy cause premature aging or contribute mechanistically to HIV-associated non-AIDS illnesses (HANA). Survival with HIV/AIDS has markedly improved by therapy combinations containing nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors, and protease inhibitors (PIs) called HAART (highly active antiretroviral therapy). Because NRTIs and PIs together prevent or attenuate HIV-1 replication, and prolong life, the population of aging patients with HIV/AIDS increases accordingly. However, illnesses frequently associated with aging in the absence of HIV/AIDS appear to occur prematurely in HIV/AIDS patients. Theories that help to explain biological aging include oxidative stress (where mitochondrial oxidative injury exceeds antioxidant defense), chromosome telomere shortening with associated cellular senescence, and accumulation of lamin A precursors (a nuclear envelop protein). Each of these has the potential to be enhanced or caused by HIV/AIDS, antiretroviral therapy, or both. Antiretroviral therapy has been shown to enhance events seen in biological aging. Specifically, antiretroviral NRTIs cause mitochondrial dysfunction, oxidative stress, and mitochondrial DNA defects that resemble features of both HANA and aging. More recent clinical evidence points to telomere shortening caused by NRTI triphosphate-induced inhibition of telomerase, suggesting telomerase reverse transcriptase (TERT) inhibition as being a pathogenetic contributor to premature aging in HIV/AIDS. PIs may also have a role in premature aging in HIV/AIDS as they cause prelamin A accumulation. Overall, toxic side effects of HAART may both resemble and promote events of aging and are worthy of mechanistic studies.
authors: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors: Rebecca A
authors: RA
authors: Torres
authors: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors: William
authors: W
authors: Lewis
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000503:physiopathology*; D019588:Aging, Premature / Q000139:chemically induced* / Q000473:pathology; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D019098:Telomerase / Q000037:antagonists & inhibitors; D059506:Telomere Shortening / Q000187:drug effects*
chemical_list: D007797:Laminin; D018894:Reverse Transcriptase Inhibitors; C084098:laminin A; D019098:Telomerase