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Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research
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13 Nov 2019
Download the PDF here
Download the PDF here
there is a desire for more holistic comprehensive care that includes HIV, but not to the exclusion of these other important concerns.
Muscle loss commonly found in aging populations may be further compounded by HIV status. Low muscle mass and function (prevalence of sarcopenia) in PWH is high (∼25%),60,61 and PWH suffer from muscle loss leading to impaired physical function and ultimately to mobility disability
more emphasis needs to be placed on patient-reported outcomes and QoL, as well as increased awareness of geriatric approaches, and the inclusion of input from PAWH when developing research priorities going forward.
women experience higher rates of falls, disability, frailty, and functional disability than men. So not only do we need to work to lessen gender disparities in terms of life expectancy, we also need to work with our patients to determine how best to optimize QoL and to be sure that QoL for WLWH is on par with that of men.
Abstract
People aging with HIV (PAWH) infection experience greater impairments in physical and cognitive function, in addition to higher rates of peripheral comorbid conditions (e.g., renal failure, diabetes, bone fracture, hypertension, cardiovascular disease, polypharmacy, and multimorbidity). While multifactorial drivers, including HIV infection itself, antiretroviral therapy-related toxicities, disparities in care, and biobehavioral factors, likely contribute, there remains an overarching question as to what are the relevant age-related mechanisms and models that could inform interventions that promote health span and life span in PAWH? This workshop was convened to hear from experts on the biology of aging and HIV researchers studying PAWH to focus on advancing investigations at the interface of HIV and Aging. In this study, we summarize the discussions from the Harvard Center for AIDS Research and Boston Claude D. Pepper cosponsored workshop on HIV and Aging, which took place in October 2018.
Kristine M. Erlandson summarized recent data on physical function and frailty in PWH, with an emphasis on distinguishing impairment, functional limitations, and disability in relation to frailty.21 Summary data were presented indicating that impairments are more pronounced among PAWH compared to uninfected
Ram Miller summarized recent and ongoing interventional approaches that target aging and senescence, including senescence pathways (e.g., rapalogs and mTOR, IGF1),2,3 efforts to reduce immunosenescence and enhance immune function,4–6 and senolytic agents that target senescent cells.
James Mitchell discussed research on adaptive responses to genotoxic stress, including effects of DNA damage and repair effects on energy metabolism, in models of premature aging.
Data were summarized indicating that loss in subcutaneous fat due to adaptive changes in energy metabolism is a common feature in segmental aging phenotypes and may be driven by cellular senescence9,10 and inflammation.11 Interestingly, fat loss associated with premature aging may, in part, be an adaptive beneficial response to DNA damage to maintain energy balance. A better understanding of which aging-related changes are primary versus adaptive is essential for targeted antiaging strategies.12,13 William J. Evans discussed sarcopenia as an age-related loss of skeletal muscle mass.14–18
Need for holistic comprehensive care
Even though many PWH who are over 50 years old are virologically suppressed, there are many psychosocial, mental health, and comorbid medical issues that have led to reductions in QoL. According to PWH who participated in the community panel, HIV is not at the top of their hierarchy of concerns. Psychosocial issues include isolation, fear of rejection, and persistent stigma (homophobia, HIV related stigma, both perceived and enacted), particularly within communities of color. Mental health issues include depression, anxiety, post-traumatic stress disorder, and cognitive decline. Medical issues (discussed elsewhere during the meeting) include diabetes, hypertension, and cancer, as well as many other illnesses associated with aging. Thus, there is a desire for more holistic comprehensive care that includes HIV, but not to the exclusion of these other important concerns.
In addition to higher rates of peripheral comorbid conditions (e.g., renal failure, diabetes, bone fracture, hypertension, CVD, and multimorbidity),40 PAWH appear to experience greater impairments in physical and cognitive function, with development of impairment in activities of daily living and frailty seen at younger than expected ages in multiple cohorts.41 For example, in the Multicenter AIDS Cohort Study, the percent of visits with a frailty phenotype dramatically increases at ages >50 among men aging with HIV compared to uninfected men,22 and despite effective ART, the decline in gait speed and grip strength was greater in men aging with HIV infection.24,42 While multifactorial drivers, including HIV infection itself, ART-related toxicities, disparities in care, and biobehavioral factors, likely contribute,43 an overarching question is how PAWH may differ from aging in people without HIV, and what are the relevant mechanisms and models that could inform interventions?
Measuring skeletal muscle loss in PAWH
Muscle loss commonly found in aging populations may be further compounded by HIV status. Low muscle mass and function (prevalence of sarcopenia) in PWH is high (∼25%),60,61 and PWH suffer from muscle loss leading to impaired physical function and ultimately to mobility disability.62 Furthermore, some report that this may also differ by sex.63,64 The rate of decline in muscle mass over a 5-year study period was similar in PWH and controls,64 yet the frequency of sarcopenia increased over a 7- to 10-year follow-up in PWH older than 50 years with the progression of sarcopenia greater in women than men.63 Standardized physical performance measures allow early detection and assessment of physical function impairments, as well as assess the effects of interventions aimed at averting physical decline and preventing mobility disability. Going beyond traditional research regarding muscle mass in PWH, we can learn more about the skeletal muscle specifically cellular and enzymatic activity changes that transpire with the use of skeletal muscle biopsies. In terms of mitochondrial markers, older male PWH have reduced oxidative enzyme activity compared to age-matched controls with 38% and 77% lower β-hydroxy acyl-CoA dehydrogenase (β-HAD) and citrate synthase activities, respectively.65 Other key enzymes of fatty acid oxidation, acyl-coA synthase, and CPT-1 are not different between male PWH and controls, but skeletal muscle oxidative stress is increased (H2O2 by 1.4 fold and oxidized cardiolipin by 1.8 fold). The importance of these findings is further demonstrated as low oxidative enzyme activity and high oxidative stress, which are related to fitness or VO2 peak perhaps suggesting that these tissue changes may contribute to the accelerated age-associated reduction in aerobic capacity in HIV. This research is one example of the mitochondrial changes in skeletal muscle in HIV-infected adults. However, there is limited information on skeletal muscle (using muscle biopsies) in HIV+ women, highlighting a clear research deficit for future studies.
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