Symptoms, Lifetime Duration of Estrogen Exposure, and Ovarian Reserve Among Women Living With HIV: A Cross-Sectional Observational Study.

ABSTRACT: This cross-sectional observational study examined associations among symptom burden, lifetime duration of estrogen exposure, and serum antimüllerian hormone (AMH) levels among women living with HIV (n = 98) using bivariate bias-corrected Pearson correlations and multiple correspondence analyses. The mostly Black (85.6%) sample of women, with a mean age of 50 years (SD 12.6 years), exhibited no significant reproductive history factors and symptom burden interrelationships or significant associations between lifetime duration of estrogen exposure and symptoms. Predictably, serum AMH levels were lower among older women; however, less predictable were its significant relationships with months living with HIV (r = -0.362), months on ART (r = -0.270), and CD4+ T-cell nadir (r = 0.347). Symptom-symptom relationships support a fatigue, pain, sleep, anxiety, and depression symptom cluster. The hypotheses were not supported by cross-sectional observation. Further studies should explore variation in relationships between HIV, estrogen exposure, ovarian reserve, and AMH levels over time.

Objectively measured physical activity among people with and without HIV in Uganda: associations with cardiovascular risk and coronary artery disease.

Background: Africa has a disproportionate burden of HIV-related cardiovascular disease. We aimed to describe physical activity in people living with HIV (PLHIV) and people without HIV (PWOH) in Uganda and characterize its relationship with the presence of computed tomography angiography-detected (CCTA) coronary artery disease (CAD). Methods: We performed a cross-sectional analysis of the Ugandan Study of HIV Effects on the Myocardium and Atherosclerosis using Computed Tomography (mUTIMA-CT) cohort. From 2017-2019, physical activity in PLHIV and PWOH was assessed by accelerometry over seven days. Participants additionally underwent CCTA. Univariable and multivariable modified Poisson regression was used to analyze the relationship between physical activity and CAD presence. Results: 168 participants were analyzed. The median (IQR) age was 57 (53-58) years old and 64% were female. Males had more moderate-to-vigorous physical activity per week [68 minutes (12-144) vs 15 minutes (0-50), P<0.001] and less light physical activity [788 minutes (497-1,202) vs [1,059 (730-1490), P=0.001] compared to females, but there was no difference by HIV status. After adjusting for age, which accounted for 10% of the variation in steps taken, and sex, no significant associations were found between physical activity and coronary plaque. Conclusion: Objectively measured physical activity was low compared to guideline recommendations, with males being somewhat more active than females and without significant differences by HIV status. Physical activity was not associated with the presence of CAD independently of age and sex.

Intramuscular versus enteral penicillin prophylaxis to prevent progression of rheumatic heart disease: Study protocol for a noninferiority randomized trial (the GOALIE trial).

BACKGROUND: Rheumatic Heart Disease (RHD) persists as a major cardiovascular driver of mortality and morbidity among young people in low-and middle-income countries. Secondary antibiotic prophylaxis (SAP) with penicillin remains the cornerstone of RHD control, however, suboptimal treatment adherence undermines most secondary prevention programs. Many of the barriers to optimal SAP adherence are specific to the intramuscular form of penicillin and may potentially be overcome by use of oral penicillin. This noninferiority trial is comparing the efficacy of intramuscular to oral penicillin SAP to prevent progression of mild RHD at 2 years. METHODS/DESIGN: The Intramuscular vs Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease (GOALIE) trial is randomizing Ugandan children aged 5 to 17 years identified by echocardiographic screening with mild RHD (Stage A or B as defined by 2023 World Heart Federation criteria) to Benzathine Benzyl Penicillin G (BPG arm, every-28-day intramuscular penicillin) or Phenoxymethyl Penicillin (Pen V arm, twice daily oral penicillin) for a period of 2 years. A blinded echocardiography adjudication panel of 3 RHD experts and 2 cardiologists is determining the echocardiographic stage of RHD at enrollment and will do the same at study completion by consensus review. Treatment adherence and study retention are supported through peer support groups and case management strategies. The primary outcome is the proportion of children in the Pen V arm who progress to more advanced RHD compared to those in the BPG arm. Secondary outcomes are patient-reported outcomes (treatment acceptance, satisfaction, and health related quality of life), costs, and cost-effectiveness of oral compared to intramuscular penicillin prophylaxis for RHD. A total sample size of 1,004 participants will provide 90% power to demonstrate noninferiority using a margin of 4% with allowance for 7% loss to follow-up. Participant enrollment commenced in October 2023 and final participant follow-up is expected in December 2026. The graphical abstract (Fig. 1) summarizes the flow of echocardiographic screening, participant enrollment and follow-up. DISCUSSION: The GOALIE trial is critical in global efforts to refine a pragmatic approach to secondary prevention for RHD control. GOALIE insists that the inferiority of oral penicillin be proven contemporarily and against the most important near-term clinical outcome of progression of RHD severity. This work also considers other factors that could influence the adoption of oral prophylaxis and change the calculus for acceptable efficacy including patient-reported outcomes and costs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05693545.

Quality of Life in Ugandan Children and Young Adults After Surgery for Congenital Heart Disease: Mixed Methods Approach.

Background: Health-related quality of life (HRQOL) is a critical issue for patients undergoing surgery for congenital heart disease (CHD) but has never been assessed in a low-income country. We conducted a cross-sectional mixed methods study with age-matched healthy siblings serving as controls at the Uganda Heart Institute. Methods: One-hundred fifteen CHD pediatric and young adult patients and sibling control participants were recruited. Health-related quality of life was assessed using the Pediatric Quality of Life Inventory Version 4.0 in participants ages 5-17 and 36-Item Short Form Survey for young adults aged 18-25. A subset of 27 participants completed face-to-face interviews to supplement quantitative findings. Results: Eighty-six pediatric (age 5-17) sibling and parent pairs completed Peds QOL surveys, and 29 young adult (age 18-25) sibling pairs completed SF-36 surveys. One third of patients had surgery in Uganda. Ventricular septal defects and tetralogy of Fallot were the most common diagnoses. Health-related quality of life scores in patients were lower across all domains compared to control participants in children. Reductions in physical and emotional domains of HRQOL were also statistically significant for young adults. Variables associated with lower HRQOL score on multivariate analysis in pediatric patients were younger age in the physical and emotional domains, greater number of surgeries in the physical domain and surgery outside Uganda in the school domain. The only predictor of lower HRQOL score in young adults was surgery outside Uganda in the social domain. Qualitative interviews identified a number of themes that correlated with survey results including abandonment by family, isolation from peers and community, financial hardship and social stigmatization. Conclusion: Health-related quality of life was lower in Ugandan patients after CHD surgery than siblings. Younger patients and those who had surgery outside of Uganda had lower HRQOL. These data have important implications for patients undergoing CHD surgery in LMIC and have potential to inform interventions.

Qualitative Description of Exercise Perceptions and Experiences Among People With Human Immunodeficiency Virus in the High-Intensity Exercise to Attenuate Limitations and Train Habits Study.

BACKGROUND: The benefits of physical activity (PA), specifically exercise, among older adults in general are well known. Yet globally, there is concern regarding limited engagement in PA, increased obesity, and frailty among older people with human immunodeficiency virus related to low levels of PA. METHODS: We conducted in-depth interviews among 30 older, sedentary people with human immunodeficiency virus participating in the ongoing High-Intensity Exercise to Attenuate Limitations and Train Habits (HEALTH study, NCT04550676) between February 2021 and August 2022. A semistructured interview guide, informed by two minds theory, which frames behavior change as an intention-behavior gap between 2 neurocognitive systems, was used to elicit data from participants. Interviews explored general exercise perceptions, self-efficacy for exercise, mobile health intervention tailoring, outcome expectations, and PA goals. Thirty interviews from 33 participants were recorded and transcribed verbatim, and deductive and inductive thematic analysis were used using Dedoose. RESULTS: Physical activity was defined as maintaining daily living activities and addressing health goals. Previous experiences with PA varied among participants and were influenced by chronic illnesses, including human immunodeficiency virus; motivation; work commitments; interest; and social support. Reported barriers to PA included antiretroviral adverse effects, comorbidities, aging, and the COVID-19 pandemic. Changes in health status, body changes, and relationships were identified as benefits of PA. Conversations with healthcare providers supporting exercise goals were perceived to be important but rarely received by the participants. CONCLUSION: Understanding how older people with human immunodeficiency virus perceive PA is crucial to developing tailored strategies and structuring service delivery within the healthcare setting to promote a physically active life.

Nurse-Led Strategy to Improve Blood Pressure and Cholesterol Level Among People With HIV: A Randomized Clinical Trial.

Importance: Despite higher atherosclerotic cardiovascular disease (ASCVD) risk, people with HIV (PWH) experience unique barriers to ASCVD prevention, such as changing models of HIV primary care. Objective: To test whether a multicomponent nurse-led strategy would improve systolic blood pressure (SBP) and non-high-density lipoprotein (HDL) cholesterol level in a diverse population of PWH receiving antiretroviral therapy (ART). Design, Setting, and Participants: This randomized clinical trial enrolled PWH at 3 academic HIV clinics in the US from September 2019 to January 2022 and conducted follow-up for 12 months until January 2023. Included patients were 18 years or older and had a confirmed HIV diagnosis, an HIV-1 viral load less than 200 copies/mL, and both hypertension and hypercholesterolemia. Participants were stratified by trial site and randomized 1:1 to either the multicomponent EXTRA-CVD (A Nurse-Led Intervention to Extend the HIV Treatment Cascade for Cardiovascular Disease Prevention) intervention group or the control group. Primary analyses were conducted according to the intention-to-treat principle. Intervention: The EXTRA-CVD group received home BP monitoring guidance and BP and cholesterol management from a dedicated prevention nurse at 4 in-person visits (baseline and 4, 8, and 12 months) and frequent telephone check-ins up to every 2 weeks as needed. The control group received general prevention education sessions from the prevention nurse at each of the 4 in-person visits. Main Outcomes and Measures: Study-measured SBP was the primary outcome, and non-HDL cholesterol level was the secondary outcome. Measurements were taken over 12 months and assessed by linear mixed models. Prespecified moderators tested were sex at birth, baseline ASCVD risk, and trial site. Results: A total of 297 PWH were randomized to the EXTRA-CVD arm (n = 149) or control arm (n = 148). Participants had a median (IQR) age of 59.0 (53.0-65.0) years and included 234 males (78.8%). Baseline mean (SD) SBP was 135.0 (18.8) mm Hg and non-HDL cholesterol level was 139.9 (44.6) mg/dL. At 12 months, participants in the EXTRA-CVD arm had a clinically significant 4.2-mm Hg (95% CI, 0.3-8.2 mm Hg; P = .04) lower SBP and 16.9-mg/dL (95% CI, 8.6-25.2 mg/dL; P < .001) lower non-HDL cholesterol level compared with participants in the control arm. There was a clinically meaningful but not statistically significant difference in SBP effect in females compared with males (11.8-mm Hg greater difference at 4 months, 9.6 mm Hg at 8 months, and 5.9 mm Hg at 12 months; overall joint test P = .06). Conclusions and Relevance: Results of this trial indicate that the EXTRA-CVD strategy effectively reduced BP and cholesterol level over 12 months and should inform future implementation of multifaceted ASCVD prevention programs for PWH. Trial Registration: ClinicalTrials.gov Identifier: NCT03643705.

Exploring the Interrelationships Between Physical Function, Functional Exercise Capacity, and Exercise Self-Efficacy in Persons Living with HIV.

PURPOSE: To determine if there were differences between the subjective and objective assessments of physical activity while controlling for sociodemographic, anthropometric, and clinical characteristics. SETTING/SAMPLE: A total of 810 participants across eight sites located in three countries. MEASURES: Subjective instruments were the two subscales of Self-efficacy for Exercise Behaviors Scale: Making Time for Exercise and Resisting Relapse and Patient-Reported Outcomes Measurement Information System, which measured physical function. The objective measure of functional exercise capacity was the 6-minute Walk Test. ANALYSIS: Both univariate and multivariant analyses were used. RESULTS: Physical function was significantly associated with Making Time for Exercise (ß = 1.76, p = .039) but not with Resisting Relapse (ß = 1.16, p = .168). Age (ß = -1.88, p = .001), being employed (ß = 16.19, p < .001) and race (ßs = 13.84-31.98, p < .001), hip-waist ratio (ß = -2.18, p < .001), and comorbidities (ß = 7.31, p < .001) were significant predictors of physical functioning. The model predicting physical function accounted for a large amount of variance (adjusted R2 = .938). The patterns of results predicting functional exercise capacity were similar. Making Time for Exercise self-efficacy scores significantly predicted functional exercise capacity (ß = 0.14, p = .029), and Resisting Relapse scores again did not (ß = -0.10, p = .120). Among the covariates, age (ß = -0.16, p < .001), gender (ß = -0.43, p < .001), education (ß = 0.08, p = .026), and hip-waist ratio (ß = 0.09, p = .034) were significant. This model did not account for much of the overall variance in the data (adjusted R2 = .081). We found a modest significant relationship between physical function and functional exercise capacity (r = 0.27). CONCLUSIONS: Making Time for Exercise Self-efficacy was more significant than Resisting Relapse for both physical function and functional exercise capacity. Interventions to promote achievement of physical activity need to use multiple measurement strategies.

Relationship between objectively measured physical activity and subclinical cardiovascular disease: a systematic review.

Introduction: The association of physical activity (PA) with subclinical cardiovascular disease (CVD) is unclear. Clarifying this relationship may inform cardiovascular prevention strategies. Methods: We performed a systematic review (CRD42021226089) using Medline, Embase, CINAHL and Cochrane (1 January 2000 to 1 September 2023). Studies published with adult populations exploring the relationship between objectively measured PA and subclinical CVD were included. Subclinical CVD was assessed using: ankle-brachial index (ABI); arterial stiffness; carotid artery disease; coronary artery atherosclerosis; endothelial function; and measures of cardiac structure and function. The Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) and Cochrane Risk of Bias tools were used for quality review. Results: Of 68 included studies, most supported an inverse relationship between PA and subclinical CVD. Arterial stiffness was the most common outcome (n=40), and 33 studies suggested that less sedentary behaviour (SB), increased PA and/or higher intensity PA was associated with less arterial stiffness. Ten studies of carotid artery disease (total n=18), six of endothelial function (n=10), two of coronary artery disease (n=3) and all of ABI (n=6) suggested that PA or less SB is associated with less subclinical disease. Five studies assessing cardiac structure/function (n=6) suggested alterations in structure/function with PA. Conclusions: PA reduces the risk of CVD events, and this systematic review demonstrates that some of the benefits may be mediated by an inverse association between PA and subclinical CVD. Interventions to increase PA are important for CVD prevention, so we provide a comprehensive overview of which surrogate outcome measures may be most useful to assess future CVD prevention interventions. PROSPERO registration number: CRD42021226089.

User-Centered Design to Develop Automated Short Message Service Messaging for Patient Support of Rheumatic Heart Disease Secondary Antibiotic Prophylaxis.

BACKGROUND: The Active Community Case Management Platform is a cloud-based technology developed to facilitate rheumatic heart disease case management by health care providers. This study aimed to design and pilot an automated short message service (SMS) intervention to support secondary prophylaxis adherence. METHODS AND RESULTS: We developed a concise library of messages to support secondary antibiotic prophylaxis. The SMS intervention used TextIT, an interface that enables users to send out interactive SMS messages at scale. The message bank was piloted in a cohort of 50 patients with rheumatic heart disease randomized into 2 groups. Group 1 received standard support (nurse-led/Active Community Case Management Platform). Group 2 received standard support plus SMS intervention for 2 months in the Lira and Gulu districts of Northern Uganda. We collected qualitative data on participants' experiences and assessed treatment adherence. Using a sequential user-centered process consisting of 4 phases (phases 1-4), we developed a message bank (n=43) deployed during our pilot study. There were no between-group differences in treatment adherence or acceptance. Interviews of participants indicated that the intervention was viewed positively. A total of 75% of SMS recipients responded to the messages, and 25% called the study staff to acknowledge receipt of text messages. CONCLUSIONS: This study has successfully developed a bank of SMS messages to support secondary antibiotic prophylaxis adherence. We have demonstrated the feasibility and acceptability of SMS technology in rheumatic heart disease care management. Future work will include integrating automated SMS into the Active Community Case Management Platform and a larger study of integrated SMS to reduce health care worker burden for patient support and improve adherence to secondary antibiotic prophylaxis.

Weight loss associated with semaglutide treatment among people with HIV.

OBJECTIVE: There is limited real-world evidence about the effectiveness of semaglutide for weight loss among people with HIV (PWH). We aimed to investigate weight change in a US cohort of PWH who initiated semaglutide treatment. DESIGN: Observational study using the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. METHODS: We identified adult PWH who initiated semaglutide between 2018 and 2022 and with at least two weight measurements. The primary outcome was within-person bodyweight change in kilograms at 1 year. The secondary outcome was within-person Hemoglobin A1c percentage (HbA1c) change. Both outcomes were estimated using multivariable linear mixed model. RESULTS: In total, 222 new users of semaglutide met inclusion criteria. Mean follow-up was 1.1 years. Approximately 75% of new semaglutide users were men, and at baseline, mean age was 53 years [standard deviation (SD): 10], average weight was 108 kg (SD: 23), mean BMI was 35.5 kg/m 2 , mean HbA1c was 7.7% and 77% had clinically recognized diabetes. At baseline, 97% were on ART and 89% were virally suppressed (viral load < 50 copies/ml). In the adjusted mixed model analysis, treatment with semaglutide was associated with an average weight loss of 6.47 kg at 1 year (95% CI -7.67 to -5.18) and with a reduction in HbA1c of 1.07% at 1 year (95% CI -1.64 to -0.50) among the 157 PWH with a postindex HbA1c value. CONCLUSION: Semaglutide was associated with significant weight loss and HbA1c reduction among PWH, comparable to results of previous studies from the general population.

Resistance Exercise Training in Individuals With and Without Cardiovascular Disease: 2023 Update: A Scientific Statement From the American Heart Association.

Resistance training not only can improve or maintain muscle mass and strength, but also has favorable physiological and clinical effects on cardiovascular disease and risk factors. This scientific statement is an update of the previous (2007) American Heart Association scientific statement regarding resistance training and cardiovascular disease. Since 2007, accumulating evidence suggests resistance training is a safe and effective approach for improving cardiovascular health in adults with and without cardiovascular disease. This scientific statement summarizes the benefits of resistance training alone or in combination with aerobic training for improving traditional and nontraditional cardiovascular disease risk factors. We also address the utility of resistance training for promoting cardiovascular health in varied healthy and clinical populations. Because less than one-third of US adults report participating in the recommended 2 days per week of resistance training activities, this scientific statement provides practical strategies for the promotion and prescription of resistance training.

Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study.

ABSTRACT: "Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR: 1.56, 95% confidence interval [95% CI] [1.13-2.15]) and reducing (HR: 1.35, 95% CI [1.13-1.62]) drinking frequency, as well as reducing HED frequency (HR: 1.58, 95% CI [1.20-2.09]) versus robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control.

Brief Report: Relationship Between Adiposity and Biomarkers of Aging and Frailty Among Adults Aging With HIV.

BACKGROUND: This study examined the relationships among adiposity, handgrip, physical function, inflammation (ie, senescence-associated secretory phenotype chemokines as biomarkers of aging and frailty), and sex hormones in aging people with HIV. METHODS: This cross-sectional exploratory study included 150 people with HIV aged ≥40 years (67.3% of participants were male). Our measures included (1) body mass index and waist circumference as measures of adiposity; (2) handgrip as a measure of muscle strength; (3) short physical performance battery as a measure of physical function; (4) interleukin-6, tumor necrosis factor alpha receptor II, high sensitivity C-reactive protein, C-X-C motif chemokine 10, and C-X3-C motif chemokine ligand 1 also known as fractalkine as senescence-associated secretory phenotype chemokines; and (5) free testosterone, estradiol, sex hormone-binding globulin, and dehydroepiandrosterone as sex hormones. Quantile regression analyses were used to identify relationships among inflammatory markers and hormones with age, adiposity, handgrip, and physical function. RESULTS: Overall, 74% (n = 111) of participants were classified as overweight or obese and 53.3% (n = 80) presented with abdominal obesity. After controlling for age and sex, body mass index was positively associated with estradiol (ß = 0.043, P < 0.01), and waist circumference was positively associated with high sensitivity C-reactive protein (ß = 2.151, P < 0.01). After controlling for sex, age was positively associated with C-X-C motif chemokine 10 (ß = 0.024, P = 0.03) and tumor necrosis factor alpha receptor II (ß = 2.205, P = 0.01). After controlling for age and sex, short physical performance battery was negatively associated with dehydroepiandrosterone (ß = -0.004, P = 0.01); no statistically significant associations were observed for handgrip. CONCLUSION: Adiposity levels and aging were associated with inflammation (ie, C-X-C motif chemokine 10, tumor necrosis factor alpha receptor II, and high sensitivity C-reactive protein) among people with HIV aged 40 years and older.

Physical activity is associated with adiposity in older adults with HIV in the modern HIV era.

OBJECTIVES: People with HIV (PWH) are aging and are experiencing higher rates of abdominal adiposity. Physical activity is an effective nonpharmacological strategy to reduce adiposity in the general aging population. Yet, the relationship between physical activity and adiposity in people with well controlled HIV is unclear. Our objective was to describe the association between objectively-measured physical activity and abdominal adiposity in PWH. METHODS: As part of the multisite, observational PROSPER-HIV study, virologically suppressed, adult PWH wore an Actigraph accelerometer for 7-10 days and completed duplicate waist and hip circumference measures. Demographic and medical characteristics were abstracted from the CFAR Network of Integrated Clinical Systems dataset. Descriptive statistics and multiple linear regressions were used to analyze the data. RESULTS: On average, our 419 PWH were 58 years of age [interquartile range (IQR): 50, 64], male (77%), Black (54%), and currently taking an integrase inhibitor (78%). PWH completed a mean of 7.06 (±2.74) days of total actigraphy wear time. They took an average of 4905 (3233, 7140) steps per day and engaged in 5.4 h of sedentary time per day. Controlling for age, sex, employment and integrase inhibitor use, the number of steps taken per day was associated with reduced abdominal adiposity ( F  = 3.27; P  < 0.001) and the hours of daily sedentary time was associated with increased abdominal adiposity ( F  = 3.24; P  < 0.001). CONCLUSIONS: Greater physical activity is associated with reduced abdominal adiposity in aging PWH. Future work should investigate how to tailor the amount, type and intensity of physical activity needed to reduce adiposity in PWH taking contemporary HIV medication. REGISTRATION NUMBER: NCT03790501.

Team-Based Qualitative Rapid Analysis: Approach and Considerations for Conducting Developmental Formative Evaluation for Intervention Design.

Qualitative rapid analysis is one of many rapid research approaches that offer a solution to the problem of time constrained health services evaluations and avoids sacrificing the richness of qualitative data that is needed for intervention design. We describe modifications to an established team-based, rapid analysis approach that we used to rapidly collect and analyze semi-structured interview data for a developmental formative evaluation of a cardiovascular disease prevention intervention. Over 18 weeks, we conducted and analyzed 35 semi-structured interviews that were conducted with patients and health care providers in the Veterans Health Administration to identify targets for adapting the intervention in preparation for a clinical trial. We identified 12 key themes describing actionable targets for intervention modification. We highlight important methodological decisions that allowed us to maintain rigor when using qualitative rapid analysis for intervention adaptation and we provide practical guidance on the resources needed to execute similar qualitative studies. We additionally reflect on the benefits and challenges of the described approach when working within a remote research team environment.ClinicalTrials.gov: NCT04545489.

Tobacco Smoking and Pack-Years Are Associated With Frailty Among People With HIV.

BACKGROUND: Tobacco smoking increases frailty risk among the general population and is common among people with HIV (PWH) who experience higher rates of frailty at younger ages than the general population. METHODS: We identified 8608 PWH across 6 Centers for AIDS Research Network of Integrated Clinical Systems sites who completed ≥2 patient-reported outcome assessments, including a frailty phenotype measuring unintentional weight loss, poor mobility, fatigue, and inactivity, and scored 0-4. Smoking was measured as baseline pack-years and time-updated never, former, or current use with cigarettes/day. We used Cox models to associate smoking with risk of incident frailty (score ≥3) and deterioration (frailty score increase by ≥2 points), adjusted for demographics, antiretroviral medication, and time-updated CD4 count. RESULTS: The mean follow-up of PWH was 5.3 years (median: 5.0), the mean age at baseline was 45 years, 15% were female, and 52% were non-White. At baseline, 60% reported current or former smoking. Current (HR: 1.79; 95% confidence interval: 1.54 to 2.08) and former (HR: 1.31; 95% confidence interval: 1.12 to 1.53) smoking were associated with higher incident frailty risk, as were higher pack-years. Current smoking (among younger PWH) and pack-years, but not former smoking, were associated with higher risk of deterioration. CONCLUSIONS: Among PWH, smoking status and duration are associated with incident and worsening frailty.

Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV.

BACKGROUND: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH. METHODS: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI. RESULTS: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption. CONCLUSIONS: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.

Appendicular Skeletal Muscle Mass Prediction in People Living With HIV: A Cross-sectional Study.

ABSTRACT: People living with HIV (PWH) experience an accelerated aging process. There is no anthropometric predictive model for appendicular skeletal muscle mass (ASM) in PWH. This study develops anthropometric models to predict and validate ASM measured by dual energy x-ray absorptiometry (DXA) in PWH; DXA scans were obtained for 125 PWH (male = 74; age >18 years) on antiretroviral therapy. Fat mass ratio was used for lipodystrophy diagnosis. A multiple stepwise linear regression considered ASM DXA as the dependent variable and validated by PRESS method. A high power of determination and low standard estimate error were found for ASM DXA -predicted (adjusted r2 = 0.84 to 0.87, standard estimate error = 1.7-1.6 kg) and high PRESS validation coefficients (Q 2PRESS = 0.84-0.86, S PRESS = 1.7-1.6 kg). The variables included were lipodystrophy diagnosis, medial calf circumference, sex, and total body weight. We present novel, reliable, and validated anthropometric models to predict ASM DXA in PWH.

The impact of COVID-19 on cardiovascular health behaviors in people living with HIV.

The COVID-19 pandemic's impact on cardiovascular health behaviors including diet, physical activity, medication adherence, and self-care among people living with HIV (PLWH) remains unknown. Using qualitative analyses, we examined the impact of the COVID-19 pandemic on cardiovascular health behaviors among PLWH. Twenty-four PLWH were enrolled in this multisite study from September to October 2020. Individuals participated in semi-structured telephone interviews that were recorded, transcribed, and coded by 4 independent coders. Codes were adjudicated and analyzed for common themes. Participants were, on average, 59.2 years old (+/-9.4), 75% African American (n = 18) and 71% male (n = 17). The pandemic altered cardiovascular disease health behaviors. PLWH changed diet based on stay-at-home orders and food access. Alterations in physical activity included transitioning from gym and group class exercise to home-based exercise. Antiretroviral adherence was maintained, even when other health behaviors wavered, suggesting resilience in PLWH that may be harnessed to maintain other health behaviors.