Chronic HIV Infection and Aging: Application of a Geroscience-Guided Approach

Abstract

: The ability of virally suppressive antiretroviral therapy use to extend the life span of people with HIV (PWH) implies that the age of PWH will also increase. Among PWH, extended survival comes at a cost of earlier onset and increased rates of aging-associated comorbidities and geriatric syndromes, with persistent inflammation and immune dysregulation consequent to chronic HIV infection and to antiretroviral therapy use contributing to an overall decrease in health span. The geroscience hypothesis proposes that the root causes of most aging-related chronic diseases and conditions is the aging process itself. Hence, therapeutically targeting fundamental aging processes could have a greater impact on alleviating or delaying aging-associated comorbidities than addressing each disease individually. Extending the geroscience hypothesis to PWH, we speculate that targeting basic mechanisms of aging will improve overall health with age. Clinical features and pathophysiologic mechanisms of chronic diseases in PWH qualitatively resemble those seen in older adults without HIV. Therefore, drugs that target any of the pillars of aging, including metformin, rapamycin, and nicotinamide adenine dinucleotide precursors, may also slow the rate of onset of age-associated comorbidities and geriatric syndromes in PWH. Drugs that selectively induce apoptosis of senescent cells, termed senolytics, may also improve health span among PWH. Preliminary evidence suggests that senescent cell burden is increased in PWH, implying that senescent cells are an excellent therapeutic target for extending health span. Recently initiated clinical trials evaluating senolytics in age-related diseases offer insights into the design and potential implementation of similar trials for PWH.

Impact of metformin on melanoma: a meta-analysis and systematic review

“…Meanwhile, metformin is currently considered an anti-aging drug because it has been shown to extend the median and maximum life span in studies conducted in several species, including C. elegans ( 36 ), drosophila ( 37 ), rodents ( 38 ), and humans ( 39 ). It is believed that metformin achieves its anti-aging properties through the evolutionary conservation of microbial-derived metabolites ( 40 ), changing the human intestinal microbiota ( 41 ), and delaying the occurrence of immune aging and related inflammation ( 42 ).…”

Effect of Drug-To-Lipid Ratio on Nanodisc-Based Tenofovir Drug Delivery to The Brain for HIV-1 Infection

“…Even though the cell viability study was done as per published protocol, it is important to note that it was a direct exposure of cells (HMC3, SH-SY5Y) to ND or free drug in in vitro conditions [ 50 ]. In clinical settings, most cART drugs are given through oral administration; therefore exposure of brain cells to cART drugs occurs after first-pass metabolism [ 58 ]. In this regard, further in vivo studies will be performed to evaluate the safety of the ND formulation in the future.…”

Characterization of data-driven geriatric syndrome clusters in older people with HIV: a Mexican multicenter cross-sectional study

“… 1 However, even though people with HIV are living longer due to combination antiretroviral therapy (cART), the treatment seems not to fully restore the induction of certain biological processes that correlate with the aging process, even when treatment goals are achieved. 2 The aging process is probably being more pronounced in people with longer expositions to HIV viral load, or a history of uncontrolled infection. 3 After the age of 50, people with HIV, particularly those who have aged with HIV, appear to exhibit an earlier occurrence or greater incidence of many aging-related conditions compared to HIV-uninfected peers.…”