Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV.

BACKGROUND: Weight gain has been well-described with integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF). Doravirine (DOR) has been identified as a relatively "weight-neutral" drug; however, there is little data describing its effect on weight change in routine clinical practice. METHODS: We conducted a retrospective chart review of weight change among people with HIV changing from an INSTI- to a non-INSTI regimen with DOR. RESULTS: At the time of ART switch, among 49 people with HIV, the mean age was 47 years, 24% were female, and 75% had HIV-1 viral load <200 copies/mL. Most (55%) people with HIV were taking bictegravir/TAF/emtricitabine prior to the switch. Although 84% switched due to concerns about weight gain, only 16% had a weight gain of ≥10% in the year preceding, and 49% had no substantial change in weight. 86% switched to DOR/lamivudine/tenofovir disoproxil fumarate. A weight decrease (-2.6% [95% CI: -5.1, -0.1%, p = .041] was seen over the year following the ART switch. Weight change prior to switch was greatest in the year 2021 compared to 2019, 2020, and 2022. CONCLUSIONS: Overall, modest changes in weight were seen following ART switch from INSTI-based regimen to a DOR-based, non-INSTI regimen. Further investigations with larger people with HIV cohorts will be helpful to guide clinical practice, while the impact of the COVID-19 pandemic on weight change should also be considered.

Efficacy and safety of tesamorelin in people with hiv on integrase inhibitors.

OBJECTIVE: Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy. DESIGN: We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily versus identical placebo among participants on INSTI-based regimens at baseline. METHODS: In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance imaging, proton magnetic resonance spectroscopy, and dual-energy x-ray absorptiometry, respectively, at baseline and 12 months. Metabolic and safety outcomes were compared between treatment arms. RESULTS: Among 38 participants on INSTI-based regimens at baseline, 15 individuals on tesamorelin and 16 individuals on placebo completed the 12-month study. Tesamorelin led to significant declines in visceral fat (median [interquartile range]: -25 [-93, -2] vs. 14 [3, 41] cm2, P = 0.001), hepatic fat (-4.2% [-12.3%, -2.7%] vs. -0.5% [-3.9%, 2.7%], P = 0.01), and trunk-to-appendicular fat ratio (-0.1 [-0.3, 0.0] vs. 0.0 [-0.1, 0.1], P = 0.03). Tesamorelin was well-tolerated with a similar frequency of adverse events including hyperglycemia between groups. CONCLUSIONS: The current analysis provides the first dedicated data on the efficacy and safety of tesamorelin among PWH on INSTI-based regimens. Despite the association of INSTI use with weight gain and adipose tissue dysfunction, tesamorelin had beneficial effects on body composition with no exacerbation of glycemic control.

Risk factors for progression from prediabetes to diabetes among older persons with HIV.

OBJECTIVE: Risk factors for progression from prediabetes (pre-DM) to diabetes (DM) among people with HIV (PWH) receiving modern antiretroviral therapy (ART) require better characterization. DESIGN: AIDS Clinical Trials Group (ACTG) A5322 (HAILO) was an observational cohort study of PWH ≥40 years old. Participants initiated ART through ACTG randomized clinical trials. METHODS: We used Cox proportional hazards regression models to identify risk factors for development of DM among HAILO participants with pre-DM. RESULTS: Among 1035 HAILO participants, 74 (7%) had pre-DM at entry and another 679 (66%) developed pre-DM during follow-up. Of 753 PWH with pre-DM, 167 (22%) developed DM. In multivariable models, the risk of developing DM was greater with higher BMI, lower CD4 count (≤200 cells/ mm3), hypertriglyceridemia, or higher waist circumference at pre-DM diagnosis (p < 0.01). CONCLUSION: Rates of pre-DM and progression to DM remain high among virally suppressed PWH receiving modern ART regimens. Traditional risks for DM, such as higher BMI or waist circumference, are associated with increased risk of incident DM among PWH with pre-DM. The association between lower CD4 and progression to DM suggests a role for advanced immunodeficiency and inflammation. Further investigation of interventions aimed at preventing DM among PWH with pre-DM is needed. Optimizing prevention and treatment for DM may be an intervenable opportunity to improve long-term outcomes for PWH.

Chronotropic Incompetence among People with HIV Improves with Exercise Training in the Exercise for Healthy Aging Study.

BACKGROUND: People with HIV (PWH) have lower exercise capacity compared to peers without HIV, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. METHODS: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus and change from baseline to 12 and 24 weeks using mixed effects models. RESULTS: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p = 0.067). AHRR was lower among PWH (91 vs 101%; difference 10%, 95% CI 1.9-18.9; p = 0.02). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p < 0.001) and was sustained at week 24 (+5, 95%CI 1-9; p = 0.008) compared to no change among controls (95%CI -4 to 4; p = 0.95; pinteraction = 0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p = 0.70). CONCLUSIONS: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

Exercise to Prevent Accelerated Vascular Aging in People Living With HIV.

Given advances in antiretroviral therapy, the mortality rate for HIV infection has dropped considerably over recent decades. However, people living with HIV (PLWH) experience longer life spans coupled with persistent immune activation despite viral suppression and potential toxicity from long-term antiretroviral therapy use. Consequently, PLWH face a cardiovascular disease (CVD) risk more than twice that of the general population, making it the leading cause of death among this group. Here, we briefly review the epidemiology of CVD in PLWH highlighting disparities at the intersections of sex and gender, age, race/ethnicity, and the contributions of social determinants of health and psychosocial stress to increased CVD risk among individuals with marginalized identities. We then overview the pathophysiology of HIV and discuss the primary factors implicated as contributors to CVD risk among PLWH on antiretroviral therapy. Subsequently, we highlight the functional evidence of premature vascular dysfunction as an early pathophysiological determinant of CVD risk among PLWH, discuss several mechanisms underlying premature vascular dysfunction in PLWH, and synthesize current research on the pathophysiological mechanisms underlying accelerated vascular aging in PLWH, focusing on immune activation, chronic inflammation, and oxidative stress. We consider understudied aspects such as HIV-related changes to the gut microbiome and psychosocial stress, which may serve as mechanisms through which exercise can abrogate accelerated vascular aging. Emphasizing the significance of exercise, we review various modalities and their impacts on vascular health, proposing a holistic approach to managing CVD risks in PLWH. The discussion extends to critical future study areas related to vascular aging, CVD, and the efficacy of exercise interventions, with a call for more inclusive research that considers the diversity of the PLWH population.

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.

Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV.

BACKGROUND: Cytomegalovirus (CMV) seropositivity is associated with poor outcomes, including physical function impairment, in people without HIV. We examined associations between CMV IgG titer and physical function in virologically suppressed people with HIV (PWH). METHODS: REPRIEVE is a double-blind randomized trial evaluating pitavastatin for primary prevention of atherosclerotic cardiovascular disease in PWH. This analysis focused on participants enrolled in a substudy with additional biomarker testing, imaging [coronary CT angiography], and physical function measures at entry. CMV IgG was measured using quantitative enzyme immunoassay, physical function by Short Physical Performance Battery, and muscle density and area by CT. Associations between CMV IgG (risk factor) and outcomes were evaluated using the partial Spearman correlation and linear and log-binomial regression. RESULTS: Among 717 participants, 82% male, the median CMV IgG was 2716 (Q1, Q3: 807, 6672) IU/mL, all above the limit of quantification. Among 631 participants with imaging, there was no association between CMV IgG and CT-based muscle density or area, controlling for age (r = -0.03 and r = -0.01, respectively; P ≥ 0.38). Among 161 participants with physical function data, higher CMV IgG was associated with poorer overall modified Short Physical Performance Battery score ( P = 0.02), adjusted for age, nadir CD4, and high-sensitivity C-reactive protein. CONCLUSIONS: Higher CMV IgG titer was associated with poorer physical function, not explained by previous immune compromise, inflammation, or muscle density or area. Further mechanistic studies are needed to understand this association and whether CMV-specific therapy can affect physical function in PWH.

Episodic disability questionnaire (EDQ) measurement properties among adults living with HIV in Canada, Ireland, United Kingdom, and United States.

BACKGROUND: The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of the Episodic Disability Questionnaire (EDQ) with adults living with HIV. METHODS: We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; > 0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; > 0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity). RESULTS: Three hundred fifty nine participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed. CONCLUSIONS: The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV.

Weight Gain After Antiretroviral Therapy Initiation and Subsequent Risk of Metabolic and Cardiovascular Disease.

BACKGROUND: Weight gain following initiation of antiretroviral therapy (ART) is common. We assessed the impact of changes in weight in the year following ART initiation with subsequent cardiometabolic disease among AIDS Clinical Trials Group (ACTG) participants. METHODS: Linear regression models were fit to examine the association between change in weight/waist circumference (WC) in weeks 0-48 and change in metabolic parameters in weeks 0-48 and 48-96. Cox proportional hazard models were fit to examine the association between changes in weight/WC in weeks 0-48 and diabetes mellitus (DM), metabolic syndrome, or cardiometabolic and cardiovascular events after week 48. RESULTS: Participants (N = 2624) were primarily male (81%) and non-White (60%). Mean weight gain from 0-48 weeks was 3.6 kg (SD 7.3); 130 participants developed DM; 360 metabolic syndrome; 424 any cardiometabolic event; 28 any cardiovascular event, over 480 weeks of follow-up. In adjusted models, total cholesterol increased by 0.63 mg/dL (95% confidence interval [CI] [.38, .089]) and LDL by 0.39 mg/dL (0.19, 0.59) per 1 kg increase in weight from weeks 0 to48. Participants who experienced >10% weight gain (vs -5% to 5%) had an increased risk of DM (hazard ratio [HR] 2.01, 95% CI [1.30, 3.08]), metabolic syndrome (HR 2.24, 95% CI [1.55, 2.62]), and cardiometabolic outcomes (HR 1.54, 95% CI [1.22, 1.95]). Participants who lost more than 5% of their baseline weight had a lower risk of incident metabolic syndrome (HR 0.67, 95% CI [0.42, 1.07]). Trends for WC were similar. CONCLUSIONS: Weight and body composition changes in the first year following ART initiation are associated with contemporaneous changes in metabolic parameters and subsequent cardiometabolic disease.

Skeletal muscle DNA methylation: Effects of exercise and HIV.

Aging, human immunodeficiency virus (HIV) infection, and antiretroviral therapy modify the epigenetic profile and function of cells and tissues, including skeletal muscle (SkM). In some cells, accelerated epigenetic aging begins very soon after the initial HIV infection, potentially setting the stage for the early onset of frailty. Exercise imparts epigenetic modifications in SkM that may underpin some health benefits, including delayed frailty, in people living with HIV (PWH). In this first report of exercise-related changes in SkM DNA methylation among PWH, we investigated the impact of 24 weeks of aerobic and resistance exercise training on SkM (vastus lateralis) DNA methylation profiles and epigenetic age acceleration (EAA) in older, virally suppressed PWH (n = 12) and uninfected controls (n = 18), and associations of EAA with physical function at baseline. We identified 983 differentially methylated positions (DMPs) in PWH and controls at baseline and 237 DMPs after training. The influence of HIV serostatus on SkM methylation was more pronounced than that of exercise training. There was little overlap in the genes associated with the probes most significantly differentiated by exercise training within each group. Baseline EAA (mean ± SD) was similar between PWH (-0.4 ± 2.5 years) and controls (0.2 ± 2.6 years), and the exercise effect was not significant (p = 0.79). EAA and physical function at baseline were not significantly correlated (all p ≥ 0.10). This preliminary investigation suggests HIV-specific epigenetic adaptations in SkM with exercise training but confirmation in a larger study that includes transcriptomic analysis is warranted.

Pharmacogenetics of weight gain following switch from efavirenz- to integrase inhibitor-containing regimens.

BACKGROUND: Excessive weight gain affects some persons with HIV after switching to integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART). We studied associations between CYP2B6 genotype and weight gain after ART switch among ACTG A5001 and A5322 participants. METHODS: Eligible participants switched from efavirenz- to INSTI-containing ART, had genotype data, and had weight data at least once from 4 weeks to 2 years post-switch. Multivariable linear mixed effects models adjusted for race/ethnicity, CD4, age, BMI and INSTI type assessed relationships between CYP2B6 genotype and estimated differences in weight change. RESULTS: A total of 159 eligible participants switched ART from 2007 to 2019, of whom 138 had plasma HIV-1 RNA < 200 copies/mL (65 CYP2B6 normal, 56 intermediate, 17 poor metabolizers). Among participants with switch HIV-1 RNA < 200 copies/mL, weight increased in all 3 CYP2B6 groups. The rate of weight gain was greater in CYP2B6 poor than in CYP2B6 normal metabolizers overall, and within 9 subgroups (male, female, White, Black, Hispanic, dolutegravir, elvitegravir, raltegravir, and TDF in the pre-switch regimen); only in Hispanic and elvitegravir subgroups were these associations statistically significant ( P  < 0.05). Compared to normal metabolizers, CYP2B6 intermediate status was not consistently associated with weight gain. CONCLUSION: CYP2B6 poor metabolizer genotype was associated with greater weight gain after switch from efavirenz- to INSTI-containing ART, but results were inconsistent. Weight gain in this setting is likely complex and multifactorial.

Energy balance and body composition after switch between integrase strand transfer inhibitors and doravirine among people with HIV.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are associated with excessive weight gain among a subset of persons with HIV (PWH), due to unclear mechanisms. We assessed energy intake (EI) and expenditure (EE) following switch off and onto INSTIs. METHODS: PWH with >10% weight gain on an INSTI-based regimen switched INSTI to doravirine for 12 weeks, then back to INSTI for 12 weeks while keeping their remaining regimen stable. Twenty-four-hour EE, EI and weight were measured on INSTI, following switch to doravirine, and upon INSTI restart. Mixed models analysed changes over time. RESULTS: Among 18 participants, unadjusted 24 h EE decreased by 83 (95% CI -181 to 14) kcal following switch to doravirine, and by 2 (-105 to 100) kcal after INSTI restart; energy balance (EE-EI) increased by 266 (-126 to 658) kcal from Week 0 to Week 12, and decreased by 3 (-429 to 423) kcal from Week 12 to Week 24. Trends toward weight loss occurred following switch to doravirine [mean -1.25 (-3.18 to 0.69) kg] and when back on INSTI [-0.47 (-2.45 to 1.52) kg]. Trunk fat decreased on doravirine [-474 (-1398 to 449) g], with some regain following INSTI restart [199 (-747 to 1145) g]. Fat-free mass decreased on doravirine [-491 (-1399 to 417) g] and increased slightly after INSTI restart [178 (-753 to 1108) g]. CONCLUSIONS: Among PWH with >10% weight gain on an INSTI, switch to doravirine was associated with a trend towards decreases in 24 h EE, weight, trunk fat mass and fat-free mass. Observed changes were not significant, but suggest a mild weight-suppressive effect of doravirine among PWH.

Polypharmacy Is Associated With Slow Gait Speed and Recurrent Falls in Older People With HIV.

BACKGROUND: Older people with human immunodeficiency virus (HIV, PWH) are prone to using multiple medications due to higher rates of medical comorbidities and the use of antiretroviral therapy (ART). We assessed the prevalence and clinical impact of polypharmacy among PWH. METHODS: We leveraged clinical data from the AIDS Clinical Trials Group A5322 study "Long-Term Follow-up of Older HIV-infected Adults: Addressing Issues of Aging, HIV Infection and Inflammation" (HAILO). We included PWH aged ≥40 years with plasma HIV RNA levels <200 copies/µL. We assessed the relationship between polypharmacy (defined as the use of 5 or more prescription medications, excluding ART) and hyperpolypharmacy (defined as the use of 10 or more prescription medications, excluding ART) with slow gait speed (less than 1 meter/second) and falls, including recurrent falls. RESULTS: Excluding ART, 24% of study participants had polypharmacy and 4% had hyperpolypharmacy. Polypharmacy was more common in women (30%) than men (23%). Participants with polypharmacy had a higher risk of slow gait speed (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.27-2.50) and increased risk of recurrent falls (OR = 2.12; 95% CI = 1.06-4.23). The risk for recurrent falls was further increased in those with hyperpolypharmacy compared with those without polypharmacy (OR = 3.46; 95% CI = 1.32-9.12). CONCLUSIONS: In this large, mixed-sex cohort of PWH aged ≥40 years, polypharmacy was associated with slow gait speed and recurrent falls, even after accounting for medical comorbidities, alcohol use, substance use, and other factors. These results highlight the need for increased focus on identifying and managing polypharmacy and hyperpolypharmacy in PWH.

Obesity among women with HIV.

PURPOSE OF REVIEW: With the introduction of novel and more potent antiretroviral therapies (ART), persons with HIV (PWH) are living longer lives and experiencing higher rates of age- and weight-related comorbidities, including cardiovascular and metabolic diseases. Women with HIV (WWH) experience disproportionate rates of obesity, as evidenced by longitudinal observational cohorts both in the United States and globally. RECENT FINDINGS: In this article, we aim to review major research findings regarding WWH and obesity over the past few years. Multiple studies have evaluated geographic changes in the obesity epidemic across the globe with focus on developing countries who have seen a drastic change in obesity rates. Other new data assessed the effect of antiretroviral therapy on WWH, the cardiovascular effects of obesity in women on ART including data from the recently published REPRIEVE Trial, and issues unique to women, such as pregnancy and the effect of menopause on WWH. SUMMARY: Comorbid cardiometabolic conditions are rapidly increasing, in correlation with the obesity epidemic among PWH. WWH may be disproportionately impacted, and experience further effects of obesity, compounded by health disparities in many areas of the world. Further research on the most effective interventions to minimize weight gains and decrease obesity among WWH are urgently needed.

Alcohol Consumption and Illicit Drug Use: Associations With Fall, Fracture, and Acute Health Care Utilization Among People With HIV Infection.

BACKGROUND: Given alcohol and/or other drug (AOD) use occurs among people with HIV (PWH), we examined its association with falls and fall-related outcomes and whether frailty moderates the association. SETTING: Northeastern US city. METHODS: We analyzed an observational cohort of PWH with current or past AOD use. Alcohol measures were any past 14-day heavy use, average alcohol/day, and days with heavy use. Drug use measures were past 30-day illicit use of cocaine, opioids, and sedatives. Repeated cross-sectional associations were estimated with separate multivariable generalized estimating equation regression models for each fall-related outcome. RESULTS: Among PWH (n = 251; mean age 52 [SD = 10]), 35% reported heavy alcohol use, 24% cocaine, 16% illicit opioids, 13% illicit sedatives, and 35% any fall; 27% were frail. Heavy alcohol use was associated with a fall (AOR = 1.49, 95% CI: 1.08 to 2.07), multiple falls (AOR = 1.55 95% CI: 1.10 to 2.19), and fall/fracture-related emergency department visit or hospitalization (AOR = 1.81, 95% CI: 1.10 to 2.97). Higher average alcohol/day and more heavy drinking days were associated with multiple falls. Illicit sedative use was associated with a fall, multiple falls, and emergency department visit/hospitalization and opioid use with fracture. Frailty moderated the association of heavy alcohol use and a fall (AOR = 2.26, 95% CI: 1.28 to 4.01 in those frail) but not in those not frail. CONCLUSION: The effect of AOD use on falls and fall-related outcomes was most pronounced with alcohol, particularly among frail PWH. Heavy alcohol, illicit sedative, and illicit opioid use are high-priority targets for preventing falls and fall-related consequences for PWH.

Impact of Integrase Strand Transfer Inhibitors on Cognition in the HAILO Cohort.

BACKGROUND: Integrase inhibitors (INSTIs) have been associated with poorer cognition in people with HIV (PWH). We examined the impact of switching to INSTIs on neuropsychological (NP) outcomes in PWH 40 years of age and older. METHODS: From the AIDS Clinical Trials Group observational cohort study, HAILO, we identified PWH who switched to INSTIs, had ≥2 NP assessments before and at least 1 after switch, and maintained viral suppression while on INSTIs. NP performance was assessed with a composite score (NPZ4) including Hopkins Verbal Learning Test (HVLT-R), Digit Symbol test (DSY), Trail Making A, and Trail Making B, while adjusting for covariates and learning effects. Outcomes changes from preswitch and postswitch periods were estimated using piecewise linear mixed models. RESULTS: Among 395 PWH (mean age 54 years, 81% male, 20% Hispanic, and 29% Black) NPZ4 increased preswitch and postswitch. There was no difference in slopes between periods for NPZ4 [preswitch 0.036/year (95% CI: 0.03 to 0.043); postswitch 0.022/year (95% CI: 0.006 to 0.005); P = 0.147]. All tests scores improved preswitch (P < 0.01). Postswitch, Trail Making A and DSY increased (all P < 0.01) without differences in rate of change (all P > 0.05). HVLT-R had a nonsignificant decrease postswitch (P = 0.22), resulting in a significant preswitch vs postswitch difference in slopes (P = 0.03). CONCLUSIONS: NP performance improved regardless of INSTI use. There was an attenuation of improvement in verbal memory in the postswitch vs preswitch period. The clinical significance of these changes is unclear but, overall, INSTIs did not have a consistent detrimental effect on NP outcomes.

Chronotropic Incompetence among People with HIV Improves with Exercise Training in the Exercise for Healthy Aging Study.

Background: People with HIV (PWH) have lower exercise capacity compared to HIV-uninfected peers, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. Methods: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus, and change from baseline to 12 and 24 weeks using mixed effects models. Results: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p=0.067). AHRR was lower among PWH (91 vs 102%; difference 11%, 95% CI 2.5-19.7; p=0.01). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p<0.001) and was sustained at week 24 (+5, 95%CI 1-9; p=0.008) compared to no change among controls (95%CI -4 to 4; p=0.95; pinteraction=0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p=0.70). Conclusions: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

Perceived Risks and Benefits and Frequency of Cannabis Use Among People with HIV in Different Legal Environments.

We sought to describe the prevalence of and motivation for cannabis use and whether legalization of cannabis impacts the frequency and perceived risks and benefits of use in people living with HIV (PWH). The study was based on two HIV clinics located in Cleveland, Ohio, and Aurora, Colorado. Participants responded to a 45-question survey, and responses were summarized in aggregate and stratified by the frequency of cannabis use and site. Three hundred ninety-seven participants completed the survey. The frequency of use was not different between the sites. Daily cannabis users compared with yearly or never users identified the benefits of cannabis as relief from stress, anxiety, or depression, improved sleep, improved creativity, improved focus or concentration, and increased energy. The benefits of pain management, improved appetite, and helping to decrease or stop other medications were selected at similar rates, regardless of the frequency of use. Daily users were less likely to identify treatment of disease as a benefit and legal problems, addiction to cannabis, impaired memory, increased use of other drugs, personal or relationship problems, decrease in intelligence, new or worsening health problems, and getting high as risks of use compared with yearly or never users. Compared with participants in Ohio, Coloradoans were more likely to identify cannabis benefits as decreasing/stopping other medications and getting high, and less likely to identify legal problems and addiction as risks. Legalization of cannabis did not affect the frequency of cannabis use in PWH. Daily cannabis users are more likely to identify benefits and less likely to identify risks of use compared with yearly or never users. A better understanding of the potential benefits and risks of cannabis use can help guide safer use of cannabis in PWH and allow physicians to provide better counseling on risk reduction.

Can statin preventative treatment inform geroscience-guided therapeutics?

Potential senotherapeutic effect of statins may lead to prevention and reduction of frailty.