Background and aims:People with HIV (PWH) experience a persistent symptom burden that negatively affects quality of life and daily functioning. Evidence examining modifiable lifestyle behaviors that may mitigate symptoms is limited. We examined longitudinal associations between objectively measured physical activity, diet quality, and symptom burden in PWH. Methods:PROSPER-HIV enrolled adults with well-controlled HIV receiving care at four Centers for AIDS Research Network of Integrated Clinical Systems sites in the United States. Participants completed annual assessments, including physical activity levels using actigraphy, dietary intake measured with three 24-h recalls generating the Healthy Eating Index-2015 (HEI-2015), and symptom burden with the HIV Symptom Index. Linear mixed models evaluated associations adjusting for age, sex at birth, race/ethnicity, and site. Results:Among 704 participants (mean age, 52.7 years; 78% male; 52% non-Hispanic Black), symptom burden remained stable over follow-up. Participants averaged 5426 ± 3149 steps/day, 164 (IQR, 67-311) minutes/week of moderate-to-vigorous physical activity (MVPA), and an HEI-2015 score of 48.1 ± 14.6. The most prevalent bothersome symptoms were muscle aches/joint pain, fatigue, sleep disturbance, anxiety, and trouble remembering. More steps/day were associated with fewer bothersome symptoms (β = -0.59 steps; P < .01), whereas more sedentary time was associated with higher symptom burden (β = 0.64; P < .01). Higher diet quality was associated with lower symptom burden (β = -0.20; P = .01). Duration of MVPA and light physical activity were not associated with symptom burden. Conclusions:Among adults with well-controlled HIV, a higher daily step count, less sedentary time, and better diet quality were associated with lower symptom burden, highlighting critical lifestyle behaviors to support symptom management in HIV care. Learning points:Among adults with well - controlled HIV, objectively measured higher daily steps and better diet quality, but not weekly moderate - to - vigorous physical activity, were associated with lower symptom burden over three years. Achievable targets to improve persistent, clinically meaningful symptoms in HIV care were identified. Clinical trial registration number:ClinicalTrials.gov [NCT03790501].

Sepsis survivors frequently experience post-discharge physical function decline and encounter logistical barriers to participation in traditional outpatient rehabilitation. This pilot study examined the feasibility, safety, and preliminary efficacy of a remotely delivered, home-based exercise program on physical function in older sepsis survivors. In this single-blinded, randomized controlled trial (RCT), sepsis survivors aged ≥ 55 years were randomized to (a) 12 weeks of avatar-guided, progressive exercise training group (EX) or (b) a standard care control group (CO). Primary outcomes were feasibility (retention, adherence) and safety (adverse events), whereas secondary outcomes were changes in the 30-s Sit-to-Stand (30SSTS), 4-Stage Balance Test (4SBT), Timed Up-and-Go (TUG) tests, and Eastern Cooperative Oncology Group/Zubrod's (ECOG/Zubrod) performance status score. Twenty-one participants were randomized to either EX (n = 10, mean age = 69.6 ± 8.5 years, 40

Carotid artery stiffness has been associated with cognitive performance; however, the association among men with HIV (MWH) remains unclear. We examined the relationship between carotid artery distensibility and cognitive performance in the Multicenter AIDS Cohort Study (MACS). We analyzed data from 717 men (459 MWH and 258 men without HIV [MWoH]) who underwent carotid artery ultrasound and completed neuropsychological testing at least twice. Carotid artery distensibility was divided into tertiles. Cognitive outcomes included psychomotor speed (Trail Making Test A), executive function (Trail Making Test B), and processing speed (Symbol Digit Modalities Test). Multivariable mixed effects linear regressions were used to estimate longitudinal associations between distensibility tertiles and cognitive scores, with adjustments for socio-demographics, cardiovascular risk factors, and HIV-related characteristics. Regardless of HIV serostatus, lower vascular distensibility was associated with older age, higher systolic and diastolic blood pressure, and greater prevalence of cardiometabolic risk factors. In fully adjusted analyses, lower carotid artery distensibility was significantly associated with slower performance on Trail Making Test A and B in MWH. These associations were weaker and not statistically significant among MWoH perhaps due to low sample size. In the combined sample, the rate of decline in executive function with age was similar across distensibility tertiles, but absolute scores were lowest in the low distensibility group. Lower carotid artery distensibility is linked to worse cognitive performance among MWH, suggesting that vascular aging may compound HIV-related cognitive decline.

Comparing ActiGraph Low-Frequency Extension (LFE) vs. normal filters on accelerometer-derived physical activity and sedentary behavior in 492 people with HIV. Participants wore ActiGraph 7-10 days; metrics (sedentary bouts, light physical activity, MVPA, steps) analyzed with both filters using Wilcoxon and Quade's ANCOVA. LFE increased MVPA (213.5 vs. 162.4 min/week) and steps (11 239 vs. 4853/day; P < 0.001) with minimal effects on sedentary bouts/light physical activity; effects were consistent across subgroups, indicating caution when comparing studies with different filters.

Introduction: Cardiovascular disease is the leading cause of death among women, and non-Hispanic Black (NHB) women exhibit accelerated vascular aging compared with non-Hispanic White (NHW) women. Traditional risk factors do not fully explain these racial disparities, prompting increased interest in reproductive history as a potential contributor. We examined race differences in reproductive history and their contribution to vascular health among midlife women using data from the Study of Women’s Health Across the Nation (SWAN). Methods: Using cross-sectional SWAN data, 2,935 postmenopausal participants ( N = 1,108 NHB, 1,827 NHW) were analyzed. Vascular health was assessed using pulse pressure (PP), estimated pulse wave velocity (ePWV), and estimated vascular overload index (eVOI). Reproductive history outcomes included age at menarche, age at first and last pregnancy, parity, breastfeeding duration, and menopause symptom count. Multivariate linear regression models evaluated whether reproductive history attenuated race differences in vascular health, adjusting for age, body mass index (BMI), and smoking status. Results: Despite similar chronological age, NHB women exhibited greater PP, ePWV, and eVOI compared with NHW women ( p < 0.001 for all). NHB women also reported a younger age at first and last pregnancy, higher parity, and shorter breastfeeding duration compared with NHW women ( p < 0.002 for all). Older age, higher BMI, and current smoking status were independently associated with accelerated vascular health across all models. Reproductive history outcomes were not associated with any vascular health indices, and inclusion of these variables did not attenuate race differences. NHB race remained a significant predictor of vascular health across all models. Conclusions: Race differences in vascular health are not explained by differences in reproductive history and persist even after adjustment for traditional risk factors. These findings merit future research on other structural and psychosocial determinants of accelerated vascular health in NHB women.

PURPOSE:To examine the construct validity of scores from the Godin Leisure-Time Exercise Questionnaire Health Contribution Score (GLTEQ HCS) as a measure of moderate-to-vigorous physical activity (MVPA) in adults with Crohn's disease (CD) and healthy controls. MATERIALS AND METHODS:Thirty-eight adults with CD (78.9% female; 41.3 ± 12.0 years) and 41 controls (73.2% female; 39.3 ± 12.0 years) completed the GLTEQ and wore an ActiGraph GT3X-BT accelerometer for 7 days. Mean differences in accelerometer outcomes across HCS categories were examined (known-groups test of construct validity). Correlations between GLTEQ HCS and accelerometer-derived MVPA (convergent validity), and light PA (LPA) and sedentary behavior (divergent validity), were examined separately by group. RESULTS:Significant differences in accelerometer-derived MVPA across the three HCS categories were observed in controls [F(2,40)=3.90, p=.03, η2=.17], but not CD. When dichotomized (active ≥24 units versus insufficiently active <24 units), medium-to-large differences in MVPA emerged for both CD (d=.62) and controls (d=.87), though this difference did not reach statistical significance in CD. GLTEQ HCS correlated with MVPA in controls (rs=.40, p=.01) but not in CD (rs=.28, p=.09), and was not associated with LPA or sedentary behavior. CONCLUSION:GLTEQ HCS demonstrated modest, context-dependent construct validity for MVPA assessment, with stronger evidence using dichotomized classification and in controls than in adults with CD.

Cardiovascular diseases remain the leading cause of death among women in the United States, and arterial stiffness is a strong predictor of cardiovascular events and mortality. Growing evidence suggests that neighborhood socioeconomic context contributes to cardiovascular risk, yet the physiological pathways linking neighborhood disadvantage to vascular health remain unclear. This study examined whether cardiorespiratory fitness (CRF) mediates the association between neighborhood deprivation (ND) and arterial stiffness in postmenopausal women. Ninety-one Black and White postmenopausal women [47 and 44, respectively, age: 64(8) yr] completed maximal treadmill testing to determine peak oxygen uptake ([Formula: see text]), and arterial stiffness was assessed via carotid-femoral pulse wave velocity (cf-PWV). ND was quantified using the area deprivation index averaged across residential addresses over the previous 25 yr. ND was associated with both lower [Formula: see text] (r = -0.45, P < 0.001) and higher cf-PWV (r = 0.28, P = 0.008). In hierarchical regression models adjusting for age, systolic blood pressure, and race, [Formula: see text] emerged as the strongest predictor of cf-PWV (B = -0.10, P = 0.003). Mediation analysis using bootstrapping revealed a significant indirect effect of ND on cf-PWV through [Formula: see text], whereas the direct effect of ND was not significant, consistent with indirect-only mediation. These findings suggest that lower CRF may partially explain the relationship between ND and vascular aging among postmenopausal women. Thus, efforts should be focused on improving access to physical activity opportunities for women facing high levels of social disadvantage.NEW & NOTEWORTHY Neighborhood disadvantage is associated with increased cardiovascular risk, yet the physiological pathways linking social environments to vascular health remain unclear. In postmenopausal women, we found that cardiorespiratory fitness mediated the relationship between neighborhood deprivation and arterial stiffness. Higher neighborhood deprivation was associated with lower fitness, which in turn was associated with greater arterial stiffness. These findings highlight cardiorespiratory fitness as a potential physiological and modifiable pathway linking adverse social environments to vascular aging.

Background: We examined associations between physical activity (PA), muscle function, and sarcopenia in older people with HIV (PWH). Setting: Multi-site PROSPER-HIV Study, including data from Seattle, WA, Cleveland, OH, and Birmingham, AL. Methods: In this cross-sectional study, we analyzed data from 148 PWH aged ≥50 years. Assessments included dual-energy X-ray absorptiometry for lean mass, handgrip strength, gait speed, chair stands, and Short Physical Performance Battery (SPPB). PA was objectively measured with ActiGraph accelerometers. Sarcopenia was defined using EWGSOP2, SDOC, and SDOC-HIV criteria. Regression models assessed associations between PA and sarcopenia, adjusting for age, sex, race, and body mass index. Results: Participants were 62.5 years old on average and 29.1% female. Sarcopenia prevalence varied widely: 1.4% under EWGSOP2, 4.1% under SDOC, and 15.2% under SDOC-HIV, with poor agreement across definitions (κ≤0.16). Participants presented a median of 105 minutes/week of moderate-to-vigorous PA (MVPA) and 4,123 steps/day. Higher MVPA was associated with lower odds of probable/confirmed sarcopenia using EWGSOP2 (OR=0.982; p <0.01). No significant associations were observed using SDOC or SDOC-HIV definitions (all p >0.05). MVPA was positively associated ( p <0.05) with handgrip strength and SPPB. Our fully adjusted model indicated that approximately 83 additional minutes of MVPA per week would be required to increase handgrip strength by 1 kg. Conclusion: Higher MVPA was associated with better muscle strength and physical performance, and with lower odds of probable/confirmed sarcopenia using EWGSOP2, whereas no significant associations were observed using SDOC or SDOC-HIV. These findings support further investigation of MVPA as a potentially important lifestyle strategy for maintaining muscle health in older PWH.

Ageing negatively affects quality of life and healthspan, and interventions are needed to slow this progressive decline. Previously, we have demonstrated the potential functional benefits of combining a genetically modified probiotic (GMP) targeting the non-canonical arm of the renin-angiotensin system (RAS) with exercise training. Initial RNAseq studies indicated the potential of the interventions to influence circadian physiology. Therefore, the objective of this study was to evaluate the expression of circadian-related genes in the tibialis anterior and soleus muscles in male and female aged rats in response to the administration of the GMP, exercise training and multiple controls. Following 12 weeks of the intervention, circadian-related genes were differentially expressed in male and female aged rats and between tissues, primarily influenced by the exercise intervention, with potential additive effects of the GMP. Several genes were also significantly associated with measures of physical performance. Thus, combining exercise with a RAS-related GMP may have potential functional benefits in late life, potentially related to circadian-related impacts within skeletal muscle.

Objectives/Goals: Heart disease is a leading cause of death in Alabama. Non-Hispanic Black (NHB) women demonstrate greater arterial stiffness than Non-Hispanic White (NHW) women. We explored whether cardiorespiratory fitness (VO2max) accounts for population differences in arterial stiffness among postmenopausal women. Methods/Study Population: We analyzed data from 57 postmenopausal women (65% NHB; age: 62±8 years; BMI: 28±4 kg/m2; blood pressure: 136±17/80±9 mmHg). VO2max was measured using maximal treadmill testing (Modified Bruce Protocol) and arterial stiffness (pulse wave velocity, PWV) via SphygmoCor XCEL. We used bias-corrected bootstrapped mediation models (5,000 resamples) to estimate the indirect effect of ancestry on PWV via VO2max, adjusting for age, body mass index, lived experience, adverse childhood exposures, and neighborhood deprivation. Given the small sample size, these analyses are exploratory. Results/Anticipated Results: NHB women had significantly lower VO2max than NHW women (18.0±3.7 vs. 23.8±4.5 mL•kg−1•min−1). VO2max was inversely associated with PWV (B = -0.10, SE = 0.04, p = 0.02, 95% CI = −0.19 to −0.01). After adjustment, ancestry was not directly associated with PWV. Neighborhood deprivation (B = 0.16, SE = 0.07, p = 0.02, 95% CI = 0.03 to 0.29) and lived experience (B = 0.10, SE = 0.04, p = 0.03, 95% CI = 0.01 to 0.19) were associated with higher PWV, even after adjusting for VO2max and risk factors. In bootstrapped mediation models, the indirect effect of ancestry on PWV through VO2max was significant (B = 0.35, SE = 0.19, 95% BCa CI = 0.03 to 0.78), consistent with partial mediation. Discussion/Significance of Impact: Cardiorespiratory fitness appears to partly account for population differences in arterial stiffness, but this cross-sectional analysis with a modest sample is exploratory. Targeting both fitness and upstream socioeconomic factors may be needed to reduce differences in women’s vascular health.

Physical activity is a promising complementary, non-invasive strategy for managing Crohn’s disease, but habitual physical activity remains poorly understood and even less is known about sedentary behavior in this population. To compare physical activity and sedentary behavior volume and patterns among adults with Crohn’s disease versus demographically matched controls. Participants (N = 79; 38 Crohn’s disease, 41 controls) completed the Godin Leisure-Time Exercise Questionnaire and wore an accelerometer for 7 days. Primary analysis included 32 matched pairs; sensitivity analyses used all participants and only those with ≥ 4 valid accelerometer wear days. MANOVAs assessed group differences in physical activity and sedentary behavior volume (self-reported moderate-to-vigorous physical activity, accelerometer-measured minutes/day in light physical activity, moderate-to-vigorous physical activity, sedentary time, steps) and pattern (accelerometer-measured moderate-to-vigorous physical activity and sedentary bout frequency and duration). Primary multivariate analyses revealed no significant group effect for overall activity volume (Wilks’ Λ = .72, p = .09) or pattern (Wilks’ Λ = .71, p = .22), including when both were modeled simultaneously (Wilks’ Λ = .61, p = .42). However, secondary and sensitivity analyses indicated Crohn’s disease participants spent less total time sedentary (≈50 min/day) and engaged in fewer sedentary breaks (p’s < .05). Moderate-to-vigorous physical activity did not differ significantly between groups. Adults with Crohn’s disease were not uniformly less active than controls, but secondary and sensitivity analyses suggested possible differences in sedentary behavior profiles. These findings support personalized physical activity recommendations for Crohn’s disease and might support interventions emphasizing frequent movement and sitting-time interruption rather than solely increasing moderate-to-vigorous physical activity.

As life expectancy for people living with HIV (PWH) has increased, there has been a rise in age-related comorbidities such as hypertension. Exercise is an important nonpharmacological strategy to counter such adverse effects of chronic HIV infection. High-intensity interval training (HIIT) has been demonstrated to be safe and efficacious in improving health outcomes in individuals with chronic illness, but data are limited in older PWH and co-morbid conditions. The primary objective of this pilot feasibility study was to assess the feasibility, efficacy, and safety of a 6-week HIIT intervention among older PWH and co-occurring hypertension. PWH were recruited from a local HIV/AIDS Clinic for a 6-week, center-based HIIT exercise intervention involving twice-weekly aerobic exercise on an upright cycle ergometer, monitored by exercise physiologists. The primary endpoint of the study was the feasibility (e.g., consent rate, attendance, adherence, dropout rate) and participant perceived benefits and barriers assessed via the Exercise Benefits and Barriers Scale. Additional endpoints included cardiorespiratory fitness (6-min walk test [6MWT]), changes in blood pressure (BP), anthropometrics (body mass index [BMI]), and ratings of pain. A total of 26 PWH were contacted, and 13 agreed to participate and were enrolled in the study. Ten of the 13 participants (76.9

Objective:Improved diet quality is increasingly important for comorbidities management and healthy aging in people with HIV (PWH). Yet, limited data exist on dietary patterns and their correlates in this population. This study aimed to (1) characterize dietary patterns among adult PWH and (2) identify demographic, clinical, and HIV-related factors associated with diet quality. Methods:We conducted a cross-sectional analysis of PWH enrolled in the PROSPER-HIV study across four U.S. academic medical centers. Dietary intake was assessed using three 24-hour dietary recalls and scored using the Healthy Eating Index-2015 (HEI-2015). Participants were categorized into tertiles based on total HEI-2015 scores. Between-group comparisons were performed using Kruskal-Wallis and chi-square tests. Factors independently associated with HEI-2015 scores were identified using multivariable linear regression. Results:A total of 491 PWH were included with a median age of 54 years; 76.4% were male. Overall diet quality was low with inadequate intake of dietary protein, fiber, and micronutrients. When classified by tertiles of HEI-2015 score, higher diet quality was characterized by greater intake of fiber, protein, and key micronutrients. Older age was independently associated with higher HEI-2015 scores (β = 0.119, p = 0.018), while Black race was associated with lower scores (β = -3.427, p = 0.008). Full-time employment and absence of current pain were marginally associated with better diet quality. Conclusions:Diet quality among PWH varies substantially and is influenced by age, race, and social determinants. Tailored nutritional strategies are needed to support healthy aging and reduce disparities in this population.

Engaging in moderate-to-vigorous physical activity (MVPA) is essential for healthy aging in people with HIV (PWH), though social determinants may influence activity levels. This cross-sectional study examined associations between neighborhood social vulnerability, social support, and MVPA among 198 PWH aged ≥ 50 from the PROSPER-HIV study across four U.S. sites. MVPA was measured with ActiGraph accelerometers (minutes/week), social vulnerability with the Social Vulnerability Index (SVI), and social support with the Multifactorial Assessment of Perceived Social Support–Short Form. Linear regression models were used to estimate the associations between study variables, adjusting for age, sex, and site. Median MVPA was 110 min/week (IQR: 48.03–237.05). Higher SVI was associated with MVPA in unadjusted models but did not reach statistical significance (β= -1.77; p = 0.053), and this association was attenuated after adjustment (p = 0.20). Social support was not associated with MVPA. Findings highlight the need for larger studies using more precise measures of structural factors relevant to physical activity among older PWH.

OBJECTIVE:To examine the relationship between body mass index (BMI), abdominal adiposity, handgrip strength and physical function in people with HIV (PWH), and to explore the potential influence of physical activity and diet on this relationship. DESIGN:Cross-sectional analyses. METHODS:The PROSPER-HIV Study was conducted at four clinical sites across the United States. Eligible participants were on antiretroviral therapy and had a viral load less than 200 copies/ml. Measures included: handgrip strength; physical function, assessed with the Short Physical Performance Battery (SPPB); BMI; abdominal adiposity, estimated using waist circumference; physical activity levels, measured using accelerometers; and diet quality, measured using triple-pass 24-h recalls. Data were analyzed using quantile regression between covariates and median of the outcomes. RESULTS:Among PWH [ n  = 409, 59 years old (51.0-65.0), 76.5% male], 71.4% were overweight or obese, 72.4% had high waist circumference, 12.7% had low handgrip strength, and 11.5% had low SPPB. After controlling for age and sex, there was a negative association between SPPB and waist circumference ( β  = -0.011, P  = 0.02). When physical activity and diet variables were considered in the model, moderate-to-vigorous physical activity (MVPA) and step count were significant ( P  < 0.05) and influenced the relationship between waist circumference and SPPB. Although there was a moderate negative correlation between waist circumference and SPPB for the lowest quartiles of MVPA and steps, this correlation weakens as the activity levels increase. CONCLUSION:Increased abdominal adiposity is associated with poorer physical function among PWH. Participants with higher MVPA and steps presented higher physical function even in the presence of high waist circumference.

Aerobic exercise lowers blood pressure (BP) with varying effects in hypertensive adults, potentially due to age-related nicotinamide adenine dinucleotide (NAD) metabolism dysregulation. This pilot randomized clinical trial (RCT) tested the efficacy of combining aerobic exercise with the NAD booster nicotinamide riboside (NR) to enhance BP control. In this double-blinded RCT, 54 sedentary adults (≥ 55 years) with mean daytime systolic BP (SBP) ≥ 130 mmHg were randomized to 6 weeks of 1000 mg/day of NR combined with 3 days/week of supervised 30-min walking exercise (NR + Ex), Placebo combined with the same exercise regimen (PL + Ex), or NR alone (NR). The primary outcome was daytime SBP. Other outcomes included pulse wave velocity (PWV), NAD catabolites, and nighttime BP. The primary comparison was between NR + Ex and PL + Ex. Of 54 participants (mean age 67 years, 61% female), 49 (NR + Ex: n = 15, PL + Ex: n = 16, NR: n = 18) completed all study visits (93% adherence to exercise and 90% to supplementation). NR + Ex (mean change = 5.19 ± 13.2 mmHg) did not reduce SBP more than PL + Ex (− 2.71 ± 10.5 mmHg). NR + Ex (− 0.31 ± 0.77 m/s) showed a trend toward a greater reduction in PWV. Levels of NAD catabolites were higher in NR groups. In a post hoc analysis, NR + Ex showed a trend toward greater nighttime BP reductions (systolic: − 9.6 ± 9.22; diastolic: − 4.51 ± 7.12 mmHg) in participants without antihypertensive medications. NR + Ex was not superior to PL + Ex in reducing BP in hypertensive middle-aged and older. However, trends toward greater nighttime BP reduction in NR + Ex in participants without antihypertensive medication warrant further investigation in a Phase IIb RCT. Graphical Abstract

Objective:Falls are a significant public health concern, particularly among older adults and people with HIV (PWH). This study examines the association between alcohol consumption and falls in PWH.Methods:The PROSPER-HIV study recruited PWH from four US sites. Participants were categorized based on Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores: none, nonhazardous, and hazardous drinking. Data collection included demographics, medical history [i.e. comorbidities, treated hypertension, estimated glomerular filtration rate (eGFR)], alcohol consumption using AUDIT-C, daily alcohol recall in grams, and self-reported falls over the previous year. Physical performance was measured using the Short Performance Physical Battery (SPPB). Statistical analyses included Pearson's correlation and Poisson regression models to estimate fall prevalence ratios, adjusting for confounders (SPPB, comorbidities, treated hypertension, and eGFR).Results:The study included 315 PWH, aged 52 +/- 12 years, with 78% male participants. Thirty-three percentage were classified as nondrinking, 50% nonhazardous, and 17% hazardous drinking. Poisson regression showed a significantly higher risk of falls [prevalence ratio: 2.12, 95% confidence interval (CI) 1.11-4.03] and recurrent falls (prevalence ratio 3.54, 95% CI 1.21-10.3) among hazardous drinking compared with nonhazardous drinking, even after adjusting for confounders. The prevalence ratios for falls per daily intake in grams was not statistically significant.Conclusion:There is a significant association between hazardous alcohol consumption and increased fall risk in PWH using AUDIT-C but not when accessing recall of alcohol consumption in grams.

BACKGROUND:Age-related morbidity, including frailty and cardiometabolic disease has become increasingly prevalent among people living with HIV (PWH), and each frailty characteristic may, independently and synergistically, play a role in cardiometabolic disease. OBJECTIVE:To evaluate the prevalence of unique frailty clusters and the prevalence ratios of cardiometabolic diseases within frailty clusters among a large diverse cohort of PWH in clinical care. DESIGN:Cross-sectional analyses within longitudinal clinical cohort. SETTING:The Center for AIDS Research Network of Integrated Clinical Systems (CNICS) from 8 Clinics PARTICIPANTS: 4,856 PWH, mean age 61 years. 16 % frail, 45 % pre-frail, 40 % robust. MEASUREMENTS:The validated, modified Fried Phenotype from patient-reported outcomes and clustering (15 clusters) of the frailty characteristics and cardiometabolic diseases (7 diseases and multimorbidity) within each cluster. RESULTS:Among 4856 PWH (age: 61 ± 6 years), the prevalence of frail, pre-frail, and robust was 16 %, 45 %, and 40 %, respectively. The most prevalent cardiometabolic disease among frail PWH was hypertension (62.6 %), followed by dyslipidemia (58.8 %) and diabetes (31.4 %). Among pre-frail PWH, the most prevalent cardiometabolic diseases were dyslipidemia (65.8 %), hypertension (61.8 %), and obesity (30.5 %). The prevalence of cardiometabolic disease among frailty clusters varied. For example, PWH in the "fatigue + poor mobility" cluster had a greater prevalence of cerebrovascular disease (PR: 2.23; 95 % CI: 1.01-4.91), diabetes (1.76; 95 % CI: 1.41-2.21), and obesity (1.66; 95 % CI: 1.35-2.05) when compared with robust PWH. Individuals in the "poor mobility" cluster had a higher prevalence of diabetes (1.37; 95 % CI: 1.15-1.64), hypertension (1.12; 95 % CI: 1.04 - 1.22), and obesity (1.38; 95 % CI: 1.17-1.61) compared with robust PWH. CONCLUSIONS:The frailty components, independently and synergistically, were associated with an increased prevalence of cardiometabolic disease. This study identified distinct frailty clusters that may be associated with increased prevalence of cardiometabolic disease among PWH.

Sepsis survivors frequently experience post-discharge physical function decline and encounter logistical barriers to participation in traditional outpatient rehabilitation. This pilot study examined the feasibility, safety, and preliminary efficacy of a remotely delivered, home-based exercise program on physical function in middle-age and older sepsis survivors. In this single-blinded, randomized controlled trial (RCT), we included sepsis survivors aged ≥55 years old and randomized them to 12 weeks of avatar-guided, progressive exercise training group (EX) or to a standard care control group (CO). Primary outcomes were feasibility (retention, adherence) and safety (adverse events), whereas secondary outcomes were changes in the 30-second Sit-to-Stand (30SSTS), 4-Stage Balance Test (4SBT), Timed Up-and-Go tests, and Eastern Cooperative Oncology Group/Zubrod's (ECOG/Zubrod) performance status score. Secondary outcomes were summarized as mean change, standard deviation, and effect sizes. Twenty-one participants were randomized to either EX (n=10, mean age=69.6±8.5 years, 40% females) or CO (n=11, mean age=72.3±7.9 years, 45% females). Mean retention in the study was 95% and adherence to exercise training was 76%. Thirty-four adverse events (AEs) occurred (EX=12; CO=22 events), including four serious AEs that were unrelated to the study. The EX group demonstrated positive direction of change in lower-extremity strength (30SSTS: 1.14±2.91 repetitions, Cohen’s d=0.393) and balance (4SBT: 5.07±4.75 seconds, d=1.07). In contrast, the CO group showed minimal change in balance on the 4SBT (0.01±4.38 seconds, d=0.003) and a negative direction of change in lower-extremity strength on the 30SSTS (−0.88±0.99 repetitions, d=−0.883). Timed Up-and-Go performance showed modest reductions in completion time in both groups (EX: −1.42±6.58 seconds, d=−0.216; CO: −1.27±2.73 seconds, d=−0.466). ECOG/Zubrod scores also showed a positive direction of change in the EX group. This pilot RCT demonstrated that a 12-week, remotely delivered exercise program was safe and feasible for middle-aged and older sepsis survivors. Preliminary signals of positive change in lower-extremity strength, balance, and functional status were observed, supporting the need for evaluation in a fully powered Phase IIb RCT targeting individuals at risk for post-discharge physical function decline. ClinicalTrials.gov NCT05568511.