Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research

Montano, Monty; Bhasin, Shalender; D’Aquila, Richard T.; Erlandson, Kristine M.; Evans, William J.; Funderburg, Nicholas T.; Justice, Amy C.; Ndhlovu, Lishomwa C.; Ojikutu, Bisola; Pahor, Marco; Pahwa, Savita; Ryan, Alice S.; Schrack, Jennifer A.; Schultz, Michael; Sebastiani, Paola; Sinclair, David; Tripp, Julia; Walker, Bruce D.; Womack, Julie A.; Yung, Raymond; Reeves, R. Keith

doi:10.1089/aid.2019.0130

Cited by 10 publications

(7 citation statements)

References 120 publications

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“…We also conducted an evaluation of markers previously shown to associate with the VACS Index based on a diverse population in terms of age and ART treatment status. In our virally suppressed cohort, we found correlations among the VACS Index with cystatin C and TNFRI levels, as well as a trends with D-dimer and TNF-α, complementing the idea that perturbations in inflammation and coagulation mechanisms are linked to morbidity and mortality progression in PAWH ( 5 ). However, we did not observe VACS index correlations with CRP, IL-6, sCD14, and sCD163 as previously described ( 71 ).…”

Section: Discussionsupporting

confidence: 77%

“…In the current era of effective suppressive combination anti-retroviral therapy (ART) regimens people aging with HIV (PAWH) have an increased risk for and earlier onset of age-related comorbidities including cardiovascular, kidney, liver, bone, and neurologic disease ( 1 , 2 ). Nearly half of the population living with HIV in the United States is older than 50 years of age and non-AIDS-defined events and age-related comorbidities are now the leading cause of mortality in the ART era ( 3 – 5 ). This demographic shift in the HIV-infected population further complicates the clinical care and management of PAWH, particularly as the increased burden of multimorbidity, frailty, geriatric syndromes, and polypharmacy become the norm ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

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Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy

et al. 2020

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The prevalence of age-related comorbidities is increased in people living with HIV, even in those well-controlled on combination antiretroviral therapy (ART). Persistent immune activation and inflammation may play pivotal roles in the pathogenesis; however, the burden of morbidities in the older HIV infected population may be exacerbated and driven by distinct mechanisms. In a cross sectional study of 45 HIV-infected participants 60 years or older, we examined the relationships between 14 immunomodulatory and inflammatory factors and the Veterans Aging Cohort Study (VACS) Index, a metric of multimorbidity and mortality comprised of age, CD4 count, hemoglobin, Fibrosis-4 [FIB-4], and estimated glomerular filtration rate [eGFR], by linear regression analysis. All participants were virally suppressed (<50 HIV RNA copies/mL), on ART, and primarily Caucasian (86.7%), and male (91.1%). Plasma levels of monocyte/macrophage-associated (neopterin, IP-10, sCD163, sCD14, and MCP-1) and glycan-binding immunomodulatory factors (galectin (Gal)-1, Gal-3, and Gal-9) were assessed, as well as inflammatory biomarkers previously linked to the VACS Index (i.e., CRP, cystatin C, TNF-α, TNFRI, IL-6, and D-dimer) for comparison. In regression analysis, higher VACS index scores were associated with higher levels of neopterin, cystatin C, TNFRI, and Gal-9 (all p < 0.05), potentially driven by correlations found with individual VACS components, including age, CD4 count, FIB-4, and eGFR. Gal-9, cystatin C, and TNFRI directly correlated with the extent of multimorbidity. Multiple correlations among markers were observed, suggesting an interplay of overlapping, but distinct, pathways. Collectively, in addition to cystatin C and TNFRI, both galectin-9 and neopterin, independently emerged as novel fluid markers of the VACS Index and Premeaux et al. Immunomodulatory Factors and HIV Comorbidities burden of comorbidity and may further guide in understanding pathogenic mechanisms of age-related disorders in older HIV-infected individuals on suppressive ART.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy

et al. 2020

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“…Collectively, this is consistent with an asynchronous aging phenotype, with some but not all features of age occurring prematurely. 8 In genetic studies using nonhuman model systems, mice lacking nicotinamide adenine dinucleotide (NAD + ) in skeletal muscle because of ablation of the rate limiting NAD biosynthetic enzyme [nicotinamide phosphoribosyltransferase (NAMPT)] displayed similar features to that observed in the skeletal muscle of our cohort of PLWH (eg, internalized nuclei and reduced PGC-1α) with a dramatic decline in physical function as the mice aged. 9 …”

Section: Introductionmentioning

confidence: 66%

Reduced Levels of NAD in Skeletal Muscle and Increased Physiologic Frailty Are Associated With Viral Coinfection in Asymptomatic Middle-Aged Adults

Tran

Pencina

Schultz

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: People living with HIV (PLWH) are disproportionately burdened with multimorbidity and decline in physiologic function compared with their uninfected counterparts, but biological mechanisms that differentially contribute to the decline in muscle function in PLWH compared with uninfected people remain understudied. Setting: The study site was Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Methods: We evaluated skeletal muscle tissue for levels of total nicotinamide adenine dinucleotide (NAD), NAD + , and nicotinamide adenine dinucleotide (NADH) in middle-aged asymptomatic PLWH, coinfected with hepatitis C virus and/or cytomegalovirus and compared them with uninfected control participants. Results: Of the 54 persons with muscle biopsy data, the mean age was 57 years with 33% women. Total NAD levels declined in skeletal muscle in association with HIV infection and was exacerbated by hepatitis C virus and cytomegalovirus coinfection, with lowest levels of total NAD, NAD + , and NADH among persons who were coinfected with all 3 viruses ( P = 0.015, P = 0.014, and 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, and P = 0.055, respectively). Coinfections were also associated with measures of inflammation (CD4/CD8 ratio: P < 0.001 and sCD163: P < 0.001) and immune activation (CD38 and human leukocyte antigen-DR expression on CD8 T cells: P < 0.001). In addition, coinfection was associated with increased physiologic frailty based on the Veteran Aging Cohort Study 1.0 index assessment ( P = 0.001). Conclusions: 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.

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“…45,46 Gender disparities in virological outcomes including survival likely contribute to this. 47,48 For example, there is a growing evidence showing that HIV+ men live longer than HIV+ women (whereas in the general population, women have longer life expectancy). 49 In a PLWH cohort of the UK, findings show consistent poorer virological outcomes in women living with HIV even in the modern ART era.…”

Section: Dovepressmentioning

confidence: 99%

“…47 Risk factors of death including substance use, psychological and mental health conditions, multimorbidity, and polypharmacy that affect men and women differently may also interact with HIV infection, which may partially explain the different survival rates. 47,48,[50][51][52] Future studies are required to identify mechanisms underlying the interaction effect of chronic HIV infection and frequent daytime sleepiness/napping in cognitive performance. It is possible that the pathophysiological processes mentioned above-sleep disturbance, inflamm-aging, and increased comorbid burden-as a result of HIV infection synergize with the effect of sleepiness and napping during daytime.…”

Section: Dovepressmentioning

confidence: 99%

Daytime Sleep Behaviors and Cognitive Performance in Middle- to Older-Aged Adults Living with and without HIV Infection

P¹,

L²,

Gao³

et al. 2022

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We investigated whether daytime sleep behaviors (DSBs) such as frequent daytime sleepiness or napping are associated with worse cognitive performance, and whether HIV infection moderates this relationship. Methods: Among 502,507 participants in the UK Biobank study, we identified 562 people living with HIV infection (PLWH; M age = 50.51±7.81; 25.09% female; 78.83% white) and extracted 562 uninfected controls who matched on age, sex, ethnic background, social-economic status, and comorbidities. DSB burden was assessed based on answers to two questions on DSBs. Participants who answered "sometimes" or "often/usually" to one of them were considered to have poor DSB burden, or otherwise were considered not having any. A composite cognition score was computed by averaging the available standardized individual test results from four neurocognitive tests: ie, a reaction time test for information processing speed, a pairs matching test for visual episodic memory, a fluid intelligence test for reasoning, and a prospective memory test. Mixed-effects models with adjustment for the variables used in extracting matched uninfected controls were performed to test the hypotheses. Results: Having poor DSB burden was associated with a 0.15 -standard deviation (SD) decrease in cognitive performance (p = 0.006). People living with HIV infection (PLWH) also performed worse on the cognitive tasks than uninfected controls, with an effect size similar to that of having poor DSB burden (p = 0.003). HIV infection significantly modified the negative association between DSB burden and cognition (p for interaction: 0.008). Specifically, the association between DSB burden and cognition was not statistically significant in uninfected controls, whereas PLWH who reported having poor DSB burden had a 0.28 -SD decrease in cognitive performance compared to PLWH who did not. Conclusion: HIV infection significantly increased the adverse association between DSBs and cognitive performance. Further studies are needed to investigate the potential mechanisms that underlie this interaction effect and whether poor DSBs and worse cognitive performance are causally linked.

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Harvard HIV and Aging Workshop: Perspectives and Priorities from Claude D. Pepper Centers and Centers for AIDS Research

Cited by 10 publications

References 120 publications

Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy

Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy

Reduced Levels of NAD in Skeletal Muscle and Increased Physiologic Frailty Are Associated With Viral Coinfection in Asymptomatic Middle-Aged Adults

Daytime Sleep Behaviors and Cognitive Performance in Middle- to Older-Aged Adults Living with and without HIV Infection

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