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People living with HIV (PLWH) are disproportionately burdened with multimorbidity and decline in physiologic function compared to their uninfected counterparts, but biological mechanisms that differentially contribute to the decline in muscle function in PLWH compared to uninfected people remains understudied. The study site was Brigham and Women’s Hospital, Harvard Medical School, Boston MA. We evaluated skeletal muscle tissue for levels of total NAD, NAD+ and NADH in middle-aged asymptomatic PLWH, coinfected with hepatitis C virus (HCV) and/or cytomegalovirus (CMV) and compared them to uninfected control participants. Of the 54 persons with muscle biopsy data, the mean age 57 years with 33% women. Total NAD levels declined in skeletal muscle in association with HIV infection, and was exacerbated by HCV and CMV coinfection, with lowest levels of total NAD, NAD+ and NADH among persons that were coinfected with all three viruses (P=0.015, P=0.014, P=0.076; respectively). Levels of total NAD, NAD+ and NADH in skeletal muscle were inversely associated with inflammation (P=0.014, P=0.013, P=0.055; respectively). Coinfections were also associated with measures of inflammation (CD4/CD8 ratio: P< 0.001 and sCD163: P< 0.001), immune activation (CD38 and HLA-DR expression on CD8 T cells: P< 0.001). Additionally, coinfection was associated with increased physiologic frailty, based on the VACS Index 1.0 assessment (P=0.001). Further research is warranted to determine the clinical relevance of preclinical deficits in NAD metabolites in skeletal muscle in association with viral coinfection and inflammation, as well as the observed association between viral coinfection and physiologic frailty.

The prevalence of age-standardized comorbidities is significantly elevated for PLWH across an array of cohorts. However, healthcare needs of older people living with (PLWH) and without (PWOH) HIV may be similar if they have similar geriatric conditions. PLWH and PWOH aged 65+ and eligible for Medicare from 7/1/2014-1/1/2015 were matched 1:1 on age, sex, race, and census region (n=7654). Cox regression assessed count of prevalent geriatric conditions (dementia, depression, falls, hip fracture, sensory deficits, osteoporosis, orthostatic hypotension, urinary incontinence, frailty, and polypharmacy), and risk for clinical or utilization outcomes (cancer, kidney disease, muscle wasting, hepatitis C, liver disease, myocardial infarction, stroke; hospitalization, nursing home and home health admission) during follow-up between 1/1/2015-12/31/2016. PLWH and PWOH are similar in count of geriatric conditions. Compared to those with none, those having 2+ geriatric conditions were similar across PLWH and PWOH in their risk of ≥1 clinical outcome (PLWH: HR 1.57 95% CI [1.29-1.90]; PWOH: HR 1.31 [1.02-1.67]), hospitalization (PLWH: HR 2.35 [1.96-2.83]; PWOH: HR 2.07 [1.65-2.60]), and home health admission (PLWH: HR 2.09 [1.58-2.76]; PWOH: HR 2.20 [1.55-3.12]). Having 2+ geriatric conditions, PWOH had 4.45 times the risk (95% CI 3.16-6.26) and PLWH had 2.88 times the risk (95% CI 2.18-3.81) of NH admission compared to no geriatric conditions. In this study, PLWH use nursing homes less than PWOH despite having a similar number of geriatric conditions and clinical outcomes. Further research to understand this apparent discrepancy will be critical to achieve equity in nursing home access.

Human immunodeficiency virus (HIV)-infected individuals are at increased risk of age-associated functional impairment, even with effective antiretroviral therapy (ART). Whether accelerated aging occurs in chronic HIV infection and the biological mechanisms that underlay aging with chronic HIV infection remains unclear. We undertook a prospective observational study of 170 middle-aged, HIV-infected ambulatory men and women with CD4+ T-cell counts of at least 350 per ml and undetectable plasma viremia while on effective antiretroviral therapy, and uninfected control participants. We measured biomarkers for inflammation and immune activation, fatigue, the Veterans Aging Cohort Study (VACS) mortality index, and conducted physical function assessment and accelerometer tracking. A subset of participants also received a skeletal muscle biopsy and computerized tomography scan. Compared to the uninfected, HIV+ participants displayed increased immune activation (P

Slower gait speed is a well-established indicator for increased risk of morbidity and mortality. However, gold standard measurement methods like the six-minute walk test (6MWT), are difficult to use in a clinical setting and may not capture important differences in free-living, volitional activity. We enrolled 46 men (23 HIV+, 23 HIV-) from a prospective observational study (MATCH) of men and women, 50–65 years old. Participants wore an activity tracker (i.e., Nokia Pulse Ox) for three weeks. Tracker data was used to create average gait speed and a measure of percent time at quartiles of maximum observed gait speed. Lab-based, 6MWT gait speed did not differ significantly by HIV status. Free-living, tracker assessed gait speed was significantly slower among HIV+ compared to uninfected participants. HIV+ participants also spent more time at lower activity levels. Free-living gait speed may provide an important digital biomarker of risks not detected by traditional lab-based measures.