Cardiovascular Disease

Investigation into cardiovascular disease (CVD) was featured prominently at the 2026 Conference on Retroviruses and Opportunistic Infections (CROI), including studies about subclinical cardiac dysfunction and its potential drivers. Perez-Blazquez and colleagues (Abstract 646) examined the association of HIV with CVD, in particular, early subclinical cardiovascular disease. Forty-two people with HIV (PWH) and 26 people without HIV (PWoH) underwent speckle tracking echocardiography, a sensitive method of detecting subclinical cardiovascular dysfunction. Parameters including left ventricular (LV) ejection fraction (EF), global myocardial work index (GWI), global myocardial work efficiency (GWE), and absolute value of left ventricular global longitudinal strain (GLSvi) were measured. Although no difference in LVEF was detected between PWH and PWoH, other parameters of LV function, including GWI (P=.001), GWE (P=.013), and GLSvi (P<.001), were lower in PWH than in PWoH. Greater viral reservoir size was associated with lower GWE. This study contributes to an improved understanding of adverse subclinical changes in myocardial function in PWH and the potential role of reservoir size in its pathogenesis. It is consistent with other studies that demonstrate an association between HIV reservoir size and comorbidities, including CVD in the 2000HIV (2000 HIV Human Functional Genomics Partnership Program) study (Abstract 326).

In another study investigating cardiac dysfunction, Omar and colleagues (Abstract 116) sought to characterize CVD in PWH in South Africa, particularly heart failure (HF), in the current antiretroviral therapy (ART) era. The investigators conducted an observational, cross-sectional study of 1008 PWH and 500 PWoH who were matched by age, sex, and presence of hypertension. The participants underwent laboratory testing and an echocardiogram. Covariates in logistic regression analyses included diabetes, smoking, and obesity. Most of the participants were female (795 PWH, 370 PWoH), and 95.3% of the PWH were on a dolutegravir (DTG)-containing regimen. Diastolic dysfunction was more prevalent in PWH than in PWoH (P = .03). HF with preserved EF (HFpEF) was more common among PWH and PWoH (8.4% and 6.6%, respectively), whereas HF with reduced EF was infrequently observed. Female sex was associated with HFpEF. For PWH, the odds ratio for HFpEF was 1.49 (95% CI, 0.96–2.35). This study provides insight into CVD phenotypes in PWH in South Africa, and its results are consistent with other studies undertaken around the world, showing a higher burden of diastolic dysfunction in PWH.

Several studies at CROI focused on atherosclerosis and myocardial infarction. In an analysis from the REPRIEVE (Pitavastatin to Prevent Cardiovascular Disease in HIV Infection) study, a large randomized controlled trial of pitavastatin vs placebo in PWH, Grinspoon and colleagues (Abstract 117) determined whether associations were present among inflammatory markers and other biomarkers at baseline and incident CVD in PWH, and whether pitavastatin use influenced these associations. A substantial percentage of participants had high levels of the following markers: high-sensitivity C-reactive protein (hsCRP; 49%), interleukin-6 (IL-6; 33%), and high-sensitivity cardiac troponin T (hs-cTnT; 35%). IL-6 (P <.001) and hs-cTnT (P = .008) were associated with major adverse cardiovascular events (MACEs), even after adjusting for traditional CVD risk factors (using the Pooled Cohort Equations [PCE] score) and statin treatment. When IL-6 and hsCRP were elevated, the risk of MACEs was greater than the risk seen when IL-6 alone or hsCRP alone was elevated. The predictive ability of the PCE score was increased with the addition of inflammatory-, cardiac-, and lipid-related biomarkers to the model. The investigators also noted that the effect of pitavastatin on incident MACEs was not affected by baseline biomarker levels. Several studies are ongoing, including analyses that will determine the effect of treatment on changes in biomarkers over time in REPRIEVE.

Hypertension

Hypertension is an established factor that contributes to CVD in PWH. Hoffman and colleagues (Abstract 676) studied the baseline prevalence and control of hypertension in the REPRIEVE study population. Hypertension was defined as having been previously diagnosed with hypertension or not having been previously diagnosed with hypertension but having a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher. Of the 7769 study participants, 36% (95% CI, 35–37) had baseline hypertension, of whom 31% had not previously been diagnosed with hypertension. Baseline hypertension was more prevalent among participants with obesity, female sex, and Black race. Of study participants who had previously been diagnosed with hypertension, 39% had uncontrolled hypertension, defined as systolic blood pressure of 140 mm Hg or higher with or without diastolic blood pressure of 90 mm Hg or higher. Using the American Heart Association criteria for stages of hypertension, 77% of participants with preexisting hypertension had stage 1 hypertension (systolic blood pressure of 130–139 mm Hg or diastolic blood pressure of 80–89 mm Hg) or greater. This study underscores that there is room for improvement in the treatment of hypertension in PWH.

Building upon this work, Martinez and colleagues (Abstract 118) studied hypertension incidence and its association with MACEs in REPRIEVE. The incident rate of hypertension was higher in the placebo arm (29.6/1000 person-years) than in the pitavastatin arm (24.7/1000 person-years). Pitavastatin significantly reduced the incidence of hypertension by 17% (P = .017). Risk factors for incident hypertension included older age, Black race in high-income countries, fasting glucose, obesity, and elevated blood pressure below the level of hypertension. Incident hypertension was associated with the first primary MACE, after adjusting for baseline atherosclerotic CVD risk (hazard ratio [HR], 2.16; 95% CI, 1.32–3.52). This study underscored the relationship between incident hypertension and MACEs and demonstrated that pitavastatin reduced incident hypertension in PWH.

Hypertension may also be related to specific ART drugs. Odongpiny and colleagues (Abstract 677) investigated the association between DTG and hypertension in a group of PWH in Uganda, most of whom (62%) were female. Before switching to DTG, the majority of the PWH were taking efavirenz (60%) or nevirapine (25%). Median systolic blood pressure and diastolic blood pressure increased by 5 mm Hg (interquartile range [IQR], −5 to 17 mm Hg for systolic blood pressure and −3 to 13 mm Hg for diastolic blood pressure) at 24 months after switching to taking dolutegravir. Switching to DTG (HR, 1.30; 95% CI, 1.02–1.64), body mass index (HR, 1.97; 95% CI, 1.27–3.05), and aged 45 years or older (HR, 1.84 for those aged 45–54 years [95% CI, 1.33–2.55] and 2.28 for those aged 55 years or older [95% CI, 1.55–3.30]) were independently associated with incident hypertension. A weight gain of more than 10% post switch was associated with a higher incidence of hypertension (HR, 1.96; 95% CI, 1.42–2.69) than a weight gain of between 5% and 10% post switch (HR, 1.73; 95% CI, 1.30–2.32). Given the high prevalence of DTG use in low-and middle-income countries, this study highlights the importance of addressing weight gain to decrease the risk of hypertension.

Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in PWH and is associated with CVD. As such, there is a strong interest in identifying therapies that can improve MASLD. Using data from the REPRIEVE study, Fichtenbaum and colleagues (Abstract 597) investigated the effect of pitavastatin on hepatic steatosis, as measured by noncontrast computed tomography. MASLD was considered present in the setting of hepatic steatosis with 1 or more elements of metabolic syndrome. The baseline prevalence of hepatic steatosis was similar in participants in the placebo arm (20%) and the pitavastatin arm (24%). No significant difference between the 2 treatment arms was noted in hepatic steatosis resolution or progression (P = .76). In addition, at 72 months, no difference was seen in the incidence of MACEs in participants with baseline hepatic steatosis and those without baseline hepatic steatosis, although the incidence of diabetes was higher if baseline hepatic steatosis was present (P <.001). This study underscores the association of hepatic steatosis with diabetes and the need for additional therapies to address hepatic steatosis in PWH.

Wegermann and colleagues (Abstract 599) addressed the importance of screening for hepatic steatosis in PWH. Given that elevated transaminase levels are not always seen in PWH with MASLD, Wegermann and colleagues studied whether measures of adiposity, including waist-to-height ratio and body roundness index (which can be easily obtained in a clinical setting) were associated with MASLD. In the HIV NASH CRN (Nonalcoholic Steatohepatitis Clinical Research Network) cohort, waist circumference had a higher discrimination ability than other adiposity measures in the overall cohort (area under the receiver operator characteristic [AUROC] curve, 0.79), and in Black PWH (AUROC curve, 0.81) and White PWH (AUROC curve, 0.74). In Hispanic PWH, waist circumference, waist-to-height ratio, and body roundness index had the same AUROC curve of 0.81. This study highlights that simple, clinically available measures are associated with hepatic steatosis and could be used to develop risk scores to identify those PWH most likely to have hepatic steatosis.

Hiranburana and colleagues (Abstract 600) also examined the need for accessible tools to identify steatotic liver disease in PWH. In a cohort of Thai PWH on integrase strand transfer inhibitor (InSTI)-based ART for 6 months or longer, they studied the associations of steatotic liver disease, as determined by transient elastography or liver ultrasound, with lipid accumulation product, hepatic steatosis index, and triglyceride-glucose index, which can be calculated using the following variables: fasting glucose, fasting triglyceride level, transaminase level, waist circumference, and body mass index. The measures had high discriminatory ability, with an AUROC curve of 0.794 (95% CI, 0.768–0.820) for the lipid accumulation product and an AUROC curve of 0.792 (95% CI, 0.765–0.819) for hepatic steatosis index. The measures were also studied separately in PWH with and without hepatitis B virus or hepatitis C virus coinfection. In PWH with hepatitis B virus or hepatitis C virus coinfection, the lipid accumulation product had the highest discriminatory ability, with an AUROC curve of 0.799. This work contributes to the development of ways to improve the detection of steatotic liver disease in PWH, especially in resource-limited settings.

Weight Gain in PWH

Although InSTI use has been associated with weight gain and incident diabetes in ART-naive PWH, less is known about the effect of InSTI use on glycemia in ARTnaive PWH with preexisting diabetes. Using data from NA-ACCORD (The North American AIDS Cohort Collaboration on Research and Design), Hwang and colleagues (Abstract 685) investigated the effects of starting an InSTI-based regimen on weight and glycemia in ARTnaive PWH with preexisting diabetes, compared with starting a nonnucleoside reverse transcriptase inhibitor (NNRTI)-or protease inhibitor (PI)-based regimen. Compared with an NNRTI-based regimen, InSTI-based and PI-based regimens resulted in significantly higher incidences of worsening glycemia, as defined by a hemoglobin A_1c (HbA_1c) increase of 0.5% or more or requiring an increase in glucose-lowering therapy. Similarly, the incidence of weight gain of 5% or more was highest in PWH on an InSTI-based or a PI-based regimen, compared with those on an NNRTI-based regimen. The results of this study could help inform the management of PWH with diabetes, in terms of understanding the potential effect of an InSTI-based regimen on glycemia.

Although the effect of the InSTI DTG on weight in PWH has been well studied, limited information exists on the effect of DTG on weight in PWoH, since DTG is not used for preexposure prophylaxis (PrEP) for HIV. Marconi and colleagues (Abstract 688) conducted a pilot study to investigate the effect of 96 weeks of DTG use on weight in 83 PWoH with human T-lymphotropic virus 1 (HTLV-1) infection, which, like HIV, causes a proinflammatory state. Study participants were randomly assigned to take daily vitamin C or DTG. After 48 weeks, participants in the vitamin C arm with symptomatic HTLV-1 infection switched to the DTG arm. No significant difference in weight from baseline to 96 weeks was noted between the 2 arms. The investigators also studied the effects of DTG on other indices, including total cholesterol level, triglyceride level, low-density lipoprotein level, high-density lipoprotein level, fat percentage, and lean tissue index, and no significant differences were noted among these indices between the 2 treatment groups. Future larger studies are needed to understand the differential effects of DTG on weight in PWH vs PWoH with other inflammatory states.

Although obesity is increasing worldwide, the literature is sparse on trends in weight change among rural populations. Kakande and colleagues (Abstract 119) studied weight changes in rural populations in Kenya and Uganda after a change in first-line ART from efavirenz to DTG. Data from 2 different studies (SEARCH [Sustainable East Africa Research in Community Health] 1.0 population-level study from 2013 to 2014 and SEARCH 2.0 population-level study from 2025) including PWH and PWoH were used. The median age was 35 years in both study populations and 14.3% of the 2013 study population and 12.8% of the 2025 study population were PWH. People on ART regimens made up 52% of the 2013 study population and 87% of the 2025 study population. Obesity was more prevalent in the 2025 study population (12.3% of women and 2.9% of men) than in the 2013 study population (4.3% of women and 0.6% of men). In addition, obesity was more prevalent in PWoH than in PWH, with the greatest prevalence values among middle-aged females with and without HIV. The change in mean body mass index from 2013 to 2025 was 0.53 kg/m² less in PWH than in PWoH (95% CI, −0.92 to −0.13) after adjusting for age, sex, and HIV status and accounting for the interaction between HIV status and time. Kakande and colleagues provided much-needed work describing weight and body mass index trends in rural East Africa, contributing to the understanding of the association of changes in first-line ART on weight in different world populations.

GLP-1 Receptor Agonists

Glucagon-like protein-1 receptor agonists (GLP-1 RAs) have transformed the management of diabetes, obesity, CVD, and numerous other obesity-related conditions. CROI 2026 highlighted these medications in PWH, including a plenary session entitled “GLP-1 Receptor Agonists: Are They a Cure for Everything?” This review sought to address the question of whether the exuberance that has been expressed about GLP-1 RAs by medical practitioners, patients, social media influencers, and the press is rational or irrational. GLP-1 RAs have been available for more than 20 years, first for the treatment of diabetes and then for the treatment of obesity and its associated conditions as the weight loss effects became clear (without the risk of hypoglycemia). These medications have become more potent over time, with impressive effects on glycemia (∼2% reduction in HbA_1c level) and weight (∼15% reduction) for semaglutide, the most widely used GLP-1 RA, and tirzepatide, a dual-RA for GLP-1 and glucose-dependent insulinotropic peptide (GIP), another gut hormone. In addition, these medications have been shown to have impressive effects on HF, MASLD, sleep apnea, chronic kidney disease, and osteoarthritis in the general population. Importantly, GLP-1 RAs have been shown to reduce the risk of cardiovascular events in people with and without diabetes, an effect that is independent of weight loss or improvements in traditional CVD risk factors, such as lipid levels, glycemia levels, and hypertension.

There are numerous other GLP-1 RA effects that could be particularly relevant for PWH. In studies that have examined the effects of these medications on markers of systemic inflammation, hsCRP has been shown to decrease by approximately 50%, even before any weight loss. The mechanisms underlying this effect are unclear but are of crucial importance for understanding the potential use of these medications in the setting of HIV. Tobacco, alcohol, and substance use disorders disproportionately affect PWH, and emerging data suggest that GLP-1 RAs at relatively low doses may decrease cravings for these substances in short-term studies in the general population. Numerous randomized trials in PWH with substance use disorders are underway. These medications do have adverse effects, with the most common being gastrointestinal upset. An emerging concern, particularly among older patients, is the impact of these medications on muscle and bone mass, which may be of particular importance in PWH, who have a high burden of frailty and osteoporosis.

Access to these medications is their Achilles’ heel. More than 25% of the world's population is potentially eligible for these medications, but cost and availability remain major challenges. With more than 60 other GLP-1-based medications in the pipeline, semaglutide becoming generic, and new, easier-to-produce formulations, the landscape will rapidly evolve over the next 10 years. There is an urgent need to understand these medications for various indications in PWH, to elucidate their risk profiles, and to implement strategies to improve access.

CROI 2026 highlighted various original studies to help close the data gaps in GLP-1 RAs in PWH. Analyses from 3 different cohorts focused on the effects of semaglutide and tirzepatide on weight and glycemic control. The DC Cohort (DC Cohort Longitudinal HIV Status Neutral Study) study (Abstract 695) examined the weight trajectories of 362 PWH who took GLP-1 RAs for at least 6 months and determined that 30% had weight loss of more than 5%, with 11% having weight loss of more than 10%. As has been observed in PWoH, weight loss was greater in those without diabetes than in those with diabetes. The reason for this heterogeneity is unclear and deserves more research.

In the general population, semaglutide and tirzepatide are the most commonly used incretin agents. In an analysis from the CNICS (Centers for AIDS Research [CFAR] Network of Integrated Clinical Systems) cohort (Abstract 697), weight loss and HbA_1c reductions were compared in people initiating semaglutide or tirzepatide. Similar to clinical trials in the general population, the effect of tirzepatide was greater than semaglutide for body weight (−6.2% vs −3.1%, respectively) and HbA_1c level (−0.25% vs −0.64%, respectively). Dosage information was not reported. Finally, in an analysis of the clinic population at the University of California San Diego using tirzepatide (Abstract 696), the mean weight loss was 32 lb over 12 months with an average dose of 10.8 mg weekly (maximum dose, 15 mg weekly). As noted in the DC Cohort study, the effect on weight was greater in those without diabetes than in those with diabetes (37 lb vs 22 lb, respectively). More than a quarter (26%) of people who initiated tirzepatide stopped within 1 year, with adverse effects and access problems being the most common reasons for discontinuation. Taken together, these findings suggest that GLP-1 RA-based medications are efficacious for weight reduction in PWH.

CROI 2026 featured presentations assessing the effects of GLP-1 RAs on other outcomes, with several excellent analyses from the CNICS cohort. In one analysis (Abstract 601), semaglutide use in PWH was associated with reductions in liver fibrosis as measured by the fibrosis-4 (FIB-4) index, especially in those with more advanced liver disease. These findings add to the potential benefits for these medications for various end-organ diseases. Another CNICS analysis (Abstract 447) examined the association of semaglutide and change in depressive symptoms. Concerns about the effects of these medications on mental health have been raised, as some users have reported mood impairment and a decrease in motivation. In this analysis, depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9) in 354 PWH before and after initiating semaglutide. Overall, PHQ-9 scores did not change after semaglutide initiation, providing some evidence of the safety of semaglutide for mental health outcomes. A CNICS study (Abstract 698) also examined the effect of semaglutide on tobacco use. GLP-1 RAs are currently being investigated for their effects on various substance use disorders, such as those associated with alcohol, opiate, and stimulant use. Some data from the general population suggest that these medications may also decrease tobacco use by decreasing craving. In a population of PWH who reported smoking (mean, 10.5 cigarettes/d) semaglutide was associated with a mean decrease of 2.7 cigarettes per day (a 26% decrease). Due to sample size, effect modification could not be adequately assessed, but effects were seen regardless of semaglutide dose, baseline body mass index, sex, and varenicline use.

Increased systemic inflammation and immune activation are thought to be major drivers of comorbidities in PWH, some of which may be due to impaired gut immune function, leading to microbial translocation. In a randomized controlled trial of liraglutide in PWH from South Africa (Abstract 115), paired duodenal and colonic biopsies were taken in 5 participants initiating liraglutide at 4 time points (pretreatment, 10 weeks after liraglutide initiation, at 4 months, and at 8 months). There was strong modulation of gut immune and epithelial cells with liraglutide treatment, with increases in duodenal CD4+ cells, reductions in CD69 expression in resident CD4+ cells, and downregulation of CD8a receptor expression. Transcriptomic analysis showed upregulation for genes related to epithelial differentiation and genes related to epithelial structure. These findings suggest that GLP-1 RAs may have potential benefits for gut immune function, which may be especially impaired in PWH. The clinical consequences of these changes need closer examination, as do dose-response effects and investigation of other GLP-1-based therapies.

Antiretroviral Adherence and HIV Comorbidities

Uncontrolled HIV replication leads to systemic inflammation and immune activation. Less well known is that imperfect ART adherence, even when HIV RNA level is suppressed, is associated with increased markers of systemic inflammation. In a prospective, observational cohort study in the ACTG (Advancing Clinical Therapeutics Globally; formerly AIDS Clinical Trials Group) network (Abstract 657), the relationship between self-reported ART adherence and serious non-AIDS events (SNAEs) was investigated over 24 years among those with HIV viral suppression (<200 copies/mL). Among 2940 participants, 260 SNAEs (126 deaths and 134 nonfatal CVD events) occurred over a median follow-up period of 6.2 years. The mean self-reported adherence rate was 97% (defined as the proportion of prescribed doses taken in the 4 days before the study visit) with approximately 2 reports of adherence per year. The median HIV RNA level was below 50 copies/mL. In the primary analysis, which used inverse probability of censor weights modeling to address potential bias, a 9% reduction in the risk of SNAEs was observed for each 10% increase in adherence. Age and the degree of HIV RNA level elevation were independently associated with SNAE. These data underscore the importance of ART adherence, even in patients who have HIV RNA suppression.

Cancer

Cancer is one of the leading causes of morbidity and mortality among PWH. Over time, the types of cancer that have been experienced by PWH have shifted, with decreases in AIDS-defining cancers and increases in non-HIV-related cancers. The REPRIEVE study examined cancer incidence in 7507 PWH from around the world (Abstract 620). The highest incident cancers were unrelated to HIV, with prostate cancer being the most common in men and breast cancer being the most common in women. Cancer risk was associated with age and cigarette smoking and was most common in high-income regions.

In an analysis from Italy (Abstract 622), cancer mortality was compared in PWH from the ICONA (Italian Cohort Naive Antiretrovirals) cohort with the general population. Over the study period (2008–2023), the cancer-related mortality rate declined among PWH, but remained higher than in the general population. These declines were most attributable to AIDS-defining cancers. However, non-AIDS-defining virus-related and non-virus-related cancer mortality rates remained high. Among virus-related cancers, human papillomavirus-related cancers (anal and cervical), lymphoma (Hodgkins and non-Hodgkins), and Kaposi sarcoma had the highest mortality rates compared with the general population. Among non-virus-related cancers, laryngeal, lung, and bladder cancers and leukemia had the highest mortality rates compared with the general population. These findings underscore the importance of cancer screening in PWH and the identification of risk factors that may drive cancer burden and mortality in PWH.

HIV and Aging

Aging in PWH was a major theme at CROI 2026, given the shifting demographics of the HIV epidemic around the world. Exercise and physical activity are established interventions to improve the health span of older people, including PWH. Although physical exercise can help to delay aging-related conditions, it can also have an impact in people with preexisting aging-related syndromes. In the GYM (Grow Your Muscle) study (Abstract 722), investigators randomly assigned PWH and PWoH with sarcopenia (as measured by bioelectrical impedance analysis) to a home-based, structured physical activity program delivered by a digital platform or to no program and examined changes in muscle mass and muscle strength over 48 weeks. Of the 196 participants who were recruited, 72% (69 PWH and 73 PWoH) completed the study. Among PWH, those randomly assigned to the physical activity intervention had significantly greater improvements in the chair stand test at 12 weeks and handgrip strength at 48 weeks, as well as improvements in muscle mass parameters, than the control group. Among PWoH, larger improvements in the chair stand test (12 and 48 weeks), handgrip strength (48 weeks), and leg extension (48 weeks) were seen in the physical activity intervention group than in the control group, but no differences were seen in the muscle mass parameters. When people who received the physical activity intervention were compared by HIV status, no differences were observed in the changes in strength parameters, but PWH had greater improvements in the muscle mass parameters than PWoH. These findings demonstrate that a home-based physical activity intervention can improve muscle mass and strength measurements in PWH. This home-delivered program using a digital platform was particularly notable for its ease of accessibility. Larger implementation studies are needed to understand the scalability of this intervention.

In addition to physical function, physical activity may improve other aspects of health, including symptoms. In the PROSPER-HIV (Impact of Physical Activity and Diet on Symptom Experience in People Living With HIV) study (Abstract 721), a CNICS-based cohort in the US, 704 older PWH had objective measurements of physical activity (7-to 10-day actigraphy) and diet (24-hour diet recall) once yearly for 3 years. Symptoms were common and did not change over the study interval, with the most bothersome and common being muscle aches (47%), insomnia (46%), fatigue (40%), neuropathy (38%), and anxiety (34%). In multivariable models, increased steps per day, decreased sedentary time, and better diet were independently associated with fewer bothersome symptoms, suggesting the possibility that increased physical activity and better diet may be crucial factors to promote healthy aging. Cellular senescence is one of the hallmarks of aging and may drive the development of aging-related diseases. Cellular senescence markers were measured in 3 groups of PWH (primary infection, chronic infection, and advanced HIV [defined as CD4+ count <100 cells/μL]) before and 1 year after ART initiation, and compared with markers in sex-and age-matched PWoH. Cellular senescence markers remained elevated in PWH with chronic or advanced infection compared with PWoH, but normalized in those with primary infection, suggesting that early treatment may be important to prevent cellular senescence in PWH. The investigators then examined the effect of the senolytic drugs dasatinib and quercetin ex vivo using a 3-day culture of peripheral blood mononuclear cells (PBMCs). Treatment with dasatinib and quercetin decreased cellular senescence biomarkers and induced senolytic activity. Whether this treatment would have similar effects in PWH in vivo and can improve physical function is not clear, but it is being evaluated in an ACTG-sponsored clinical trial (NCT07144293).

As PWH age throughout the world, conditions such as osteoporosis and frailty are increasingly recognized in settings with a high burden of HIV, such as in sub-Saharan Africa. In a study of 179 older women with HIV in Kenya (Abstract 732), 56% had osteoporosis based on spine and hip dual-energy X-ray absorptiometry using the NHANES (National Health and Nutrition Examination Survey) Black female reference database. Higher body mass index and type 2 diabetes were associated with a lower prevalence of osteoporosis, whereas longer duration of ART tended to be associated with an increased osteoporosis prevalence. Tenofovir disoproxil fumarate-based regimens tended to be associated with lower bone-mineral density, but given that 73% were receiving this type of regimen, this factor could not be adequately evaluated. Additional studies are needed to understand whether this high prevalence of osteoporosis will translate into a higher risk of fracture. Nonetheless, given the very high prevalence of osteoporosis in this population, and interventions that can reduce fracture risk, dual-energy X-ray absorptiometry screening and osteoporosis treatment protocols will be essential to decrease fracture risk in older women with HIV in Africa.

Frailty is an important aging-related condition that will affect an increasing number of PWH in Africa. In a crosssectional study in urban Tanzania that enrolled 197 women and 196 men with HIV (Abstract 717), the majority of whom were in their 50s, the overall prevalence of frailty was 14% and prefrailty was 49%. Factors associated with frailty or prefrailty were female sex, shorter ART duration, hypertension, lower weight and overweight/obesity, less social support, and increased depressive symptoms. Additional work is needed to understand whether interventions can improve physical function in this population.