Joseph B. Margolick

Study Objectives: The landscape of HIV infection has shifted dramatically over the last few decades. An extended lifespan has led to an increase in comorbidities, including disorders of sleep. While self-reported sleep disturbances in people living with HIV are common, differences in sleep architecture between those living with and without HIV have not been previously described. Methods: Polysomnography data from the Multicenter AIDS Cohort Study were used to characterize differences in sleep architecture between men living with and without HIV. Parameters assessed included total sleep time, sleep stage distribution, arousal index, and frequency of sleep stage transitions. Multivariable regression was employed to adjust for demographic variables and explore effect modification by sleep-disordered breathing (SDB) severity. Results: Compared to men without HIV (N = 349), men with HIV (N = 447) exhibited comparable total sleep time, but lower sleep efficiency and greater wake time after sleep onset. Independent of HIV status, SDB was associated with a greater percentage of N1 sleep and lower percentages of N2 and REM sleep. However, those with both HIV and severe SDB displayed the lowest sleep efficiency, the highest percentage of N1 sleep, and the lowest frequency of sleep stage transitions from nonrapid eye movement (non-REM)-to-REM sleep compared to all other HIV and SDB subgroups. Conclusions: This study found an independent association between HIV, SDB, and altered sleep architecture, characterized by lower sleep efficiency, greater time in stage N1 sleep, and higher sleep stage instability. Further research is needed on the potential health implications of disrupted sleep in those with HIV and SDB.

Integrating antiretroviral therapy (ART) into HIV care dramatically extended the lifespan for people living with HIV (PWH). Improving the health span requires understanding aging, HIV, associated comorbid conditions, and concurrent treatments. The 14^th annual International Workshop on HIV and Aging on October 26-27, 2023 included podium presentations on: Sarcopenia Biology, Pathophysiology, Prevention and Treatment; Long-acting ART; Central Nervous System (CNS) Complications; Asymptomatic Neurocognitive Impairment (ANI); Mental Health; Loneliness; and Resilience. Presentations highlighted persistent concerns for PWH including sarcopenia and frailty, mental health, loneliness, and cognition. Presenters encouraged prioritizing mental health treatment, reducing social isolation, and research on resiliency

Although poor sleep quality is associated with lower CD4+ T cell counts among people living with HIV (PLWH), the association between objective sleep metrics and T lymphocyte subset counts is unknown. We evaluated the association between polysomnography (PSG) derived sleep metrics and T lymphocyte subpopulations in a cohort of men living with HIV. Virally suppressed men living with HIV participating in the Multicenter AIDS Cohort Study underwent home overnight PSG. We assessed the association of PSG parameters with CD4+ and CD8+ T cell counts and the CD4+/CD8+ T cell ratio. Overall, 289 men with mean (±SD) age 55.3 ±11.3 years and mean CD4+ T cell count 730 ±308 cells/mm³ were evaluated. Total sleep time (TST) was significantly associated with CD8+ but not CD4+ T cell counts. After adjusting for age, race, depressive symptoms, antidepressant use, and non-nucleoside reverse transcriptase inhibitors use, every hour of shorter TST was associated with an additional 33 circulating CD8+ T cells/mm³ (p=0.05) and a 5.6% (p=0.0007) decline in CD4+/CD8+ T cell ratio. In adjusted models, every hour of shorter REM sleep was associated with an additional 113 CD8+ T cells/mm³ (p=0.02) and a 15.1% lower CD4+/CD8+ T cell ratio (p=0.006). In contrast, measures of sleep efficiency and sleep-disordered breathing were not associated with differences in T lymphocyte subpopulations. Our findings suggest that shorter TST and REM sleep durations are associated with differences in T lymphocyte subpopulations among men living with HIV. Addressing sleep may reflect a novel opportunity to improve immune function in PLWH.

Along with multiple chronic comorbidities, sleep disorders are prevalent in people living with human immunodeficiency virus (HIV) infection. The goal of this study was to establish methods for assessing sleep quality and breathing-related disorders using self-applied home polysomnography in people with and without HIV. Self-applied polysomnography was conducted on 960 participants in the Multicenter AIDS Cohort Study (MACS) using the Nox A1 recorder to collect data on the frontal electroencephalogram (EEG), bilateral electrooculograms, and a frontalis electromyogram during sleep. Breathing patterns were characterized using respiratory inductance plethysmography bands and pulse oximetry. Continuous recordings of the electrocardiogram were also obtained. All studies were scored centrally for sleep stages and disordered breathing events. Successful home polysomnography was obtained in 807 of 960 participants on the first attempt and 44 participants on the second. Thus, a successful polysomnogram was obtained in 851 (88.6%) of the participants. Reasons for an unsuccessful study included less than 3 h of data on oximetry (34.6%), EEG (28.4%), respiratory inductance plethysmography (21.0%), or two or more of these combined (16.0%). Of the successful studies (N = 851), signal quality was rated as good, very good, or excellent in 810 (95.2%). No temporal trends in study quality were noted. Independent correlates of an unsuccessful study included black race, current smoking, and cocaine use. Home polysomnography was successfully completed in the MACS demonstrating its feasibility in a community cohort. Given the burden of in-lab polysomnography, the methods described herein provide a cost-effective alternative for collecting sleep data in the home.

C-reactive protein (CRP) is an inflammatory biomarker associated with all-cause mortality and morbidities such as cardiovascular disease. CRP is increased with HIV infection and thought to increase with age, though trajectories of CRP with aging have not been well characterized. We investigated trajectories of CRP in men from the Multicenter AIDS Cohort Study, according to HIV infection and HIV viral load status. CRP measurements from 12 250 serum samples, provided by 2132 men over a span of 30 years, were categorized by HIV status at sample collection: HIV uninfected (HIV−, n = 1717), HIV infected with undetectable RNA (HIV+ suppressed, n = 4075), and detectable HIV RNA (HIV+ detectable, n = 6458). Age-related trajectories of CRP were fit to multivariable linear mixed models; we tested for differences in trajectories by HIV status. CRP increased with age in all sample groups. HIV+ detectable and HIV+ suppressed samples had higher CRP than HIV− samples throughout the observed age range of 20–70 years (p < .05). CRP concentrations at age 45 years were 38% (95% CI: 26%–50%) and 26% (15%–38%) higher in HIV+ detectable and HIV+ suppressed samples, respectively, relative to HIV− samples. HIV+ detectable samples showed more rapid linear increases with age (8% higher/decade, 0.3%–16%) than HIV− samples. We observed higher concentrations of CRP across 5 decades of age in men living with HIV, and steeper increases with age in men with detectable HIV RNA, relative to HIV− men. These results are consistent with a contribution of inflammation to the higher risk of age-related comorbidities with HIV infection.

The extent to which human immunodeficiency viral (HIV) infection is independently associated with myocardial disease in the era of combination antiretroviral therapy (cART) remains understudied. We assessed differences in cardiovascular magnetic resonance imaging (CMR) metrics among people living with HIV (PLWH) and without HIV (PWOH). Among 436 participants (aged 54.7 ± 6.0 years, 29% women) from three cohorts, we acquired CMR cines, late gadolinium enhancement (LGE), and T1 mapping. Multivariable linear regressions were used to evaluate associations between HIV serostatus and CMR metrics. Baseline characteristics were similar by HIV serostatus; 63% were PLWH of whom 88% received cART and 73% were virally suppressed. Median left ventricular ejection fraction was normal and similar by HIV serostatus (73%, PWOH vs. 72%, PLWH, P = 0.43) as were right ventricular function, biventricular volumes, and masses. LGE prevalence was similar (32%, PWOH vs. 36%, PLWH, P = 0.46) with low scar extents (4.1, PWOH vs. 4.9 g, PLWH, P = 0.51) and few ischaemic scars (3%, PWOH vs. 4%, PLWH, P = 0.70). Extracellular volume fraction (ECV) was higher among PLWH (29.2 ± 4.1% vs. 28.3 ± 3.7%, P = 0.04) as was indexed maximum left atrial (LA) volume (LAVI, 29.7 ± 10.3 vs. 27.8 ± 8.7 mL/m², P = 0.05). After multivariate adjustment, ECV was 0.84% higher among PLWH (P = 0.05) and LAVI was 2.45 mL/m² larger (P = 0.01). HIV seropositivity and higher ECV contributed to higher LAVI (P < 0.02). There were no associations between HIV disease severity and CMR metrics among PLWH. HIV seropositivity was independently associated with greater diffuse non-ischaemic fibrosis and larger LA volume but no other differences in CMR metrics.

The inflammatory context of HIV infection has been posited to contribute to the higher comorbidity risk noted in HIV-infected populations. One possible pathway may involve 1,25-dihydroxyvitamin D [1,25(OH)2D], which plays a wide biologic role in many tissues. We sought to investigate whether inflammation was associated with vitamin D metabolites in a cohort of HIV-infected (HIV+) men receiving treatment and HIV-uninfected (HIV-) men. Vitamin D metabolites, including 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)2D, were measured along with 24 inflammatory markers among Multicenter AIDS Cohort Study participants. Exploratory factor analysis reduced inflammatory marker data to a smaller set of inflammatory processes (IPs). Multivariate linear regression was used to evaluate associations between vitamin D metabolites and IPs. There were 466 HIV+ and 100 HIV- men, who contributed 658 stored samples from 1998 to 2008. We found three IPs with IP 1 characterized by sTNF-R2, sIL-2Rα, sCD27, BAFF, sgp130, sCD14, CXCL10 (IP-10), and sIL-6R. While none of the three IPs was associated with 25(OH)D levels in either HIV+ or HIV-, higher levels of IP 1 were significantly associated with the reduced levels of 1,25(OH)2D in HIV+, and a similar although nonsignificant trend was seen in HIV-. The association between 1,25(OH)2D and inflammation found among HIV-infected men suggests a possible mechanism whereby inflammation leads to the increased comorbidity risk noted among HIV-infected individuals.

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