Background: Kidney disease is an increasingly important comorbidity in people with HIV (PWH), owing to its association with mortality and cardiovascular (CV) disease, a leading cause of non-AIDS-related death. Sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have demonstrated renal and cardiovascular protective effects in the general population, but evidence in PWH remains scarce. We aimed to evaluate the safety and clinical effects of dapagliflozin in PWH with chronic kidney disease (CKD). Methods: We enrolled adult PWH with an estimated glomerular filtration rate (eGFR) of 25–75 mL/min/1.73 m² who were receiving stable antiretroviral therapy and had sustained HIV virological suppression. Participants received dapagliflozin 10 mg once daily according to routine clinical practice. Safety and efficacy outcomes, blood and urine biochemistry, 24-hour ambulatory blood pressure monitoring, adipose and muscle composition, and body water distribution were assessed. Analyses were performed in the overall cohort and stratified by gender and diabetes status. Results: Thirty-seven participants were included. Most were cisgender men (78%), and the median age was 60 years. One participant discontinued treatment because of dizziness. Renal parameters showed a consistent, although non-significant, trend toward improvement. Haematocrit and haemoglobin increased significantly in the overall cohort (both p < 0.001). HDL cholesterol increased significantly among participants with diabetes (p = 0.034). Body mass index (BMI) decreased from 26.48 kg/m² (IQR 24.00–29.38) to 26.22 kg/m² (IQR 23.58–28.42; p < 0.001), and waist circumference decreased from 102.3 cm (IQR 92.4–108.8) to 101.6 cm (IQR 90.85–107.55; p = 0.009). In men, rectus femoris cross-sectional area decreased significantly from 7.12 cm² to 6.65 cm² (p = 0.033), although no significant DXA-assessed changes in muscle composition were observed. All ultrasound-assessed abdominal fat layers decreased, but only omental fat thickness reached statistical significance, decreasing from 75.2 mm (IQR 39.6–81.9) to 58.6 mm (IQR 44.1–73.5; p = 0.029). The extracellular water-to-total body water ratio increased significantly in the overall cohort, from 0.378 (IQR 0.372–0.387) to 0.379 (IQR 0.372–0.387; p = 0.044), and among participants with diabetes, from 0.381 (IQR 0.375–0.388) to 0.383 (IQR 0.383–0.392; p = 0.014). Conclusions: In this cohort of PWH with CKD, dapagliflozin was well tolerated and associated with a trend toward improved renal function, together with significant reductions in BMI, waist circumference and omental fat thickness, a marker of cardiometabolic risk. Longer follow-up and larger studies are needed to confirm these benefits and determine their impact on cardiovascular outcomes.

Background: Gender differences in aging among people with HIV (PWH) remain poorly characterized. Women with HIV (WWH) may experience more complex aging trajectories, due to the interplay of biological, clinical, and psychosocial factors. In this context, we aimed to investigate gender-specific determinants of frailty among older people with HIV, with a particular focus on women, to better inform tailored clinical care. Methods: Cross-sectional analysis of the Over50 Cohort, including PWH aged ≥50 years from two tertiary hospitals in Spain. Participants underwent a comprehensive geriatric assessment across demographic, clinical, functional, cognitive, psychological, and social domains. Gender-stratified multivariable analyses examined frailty (by Fried criteria) and associated factors. Results: Among 588 participants, 139 (23.6%) were cisgender WWH. Despite younger age and better immune status, WWH showed higher prevalence of frailty (17% vs. 9%), musculoskeletal disease (47% vs. 28%), depressive symptoms (45% vs. 30%), sleep disturbances (10% vs. 5%), and cognitive complaints (23% vs. 11%). Men with HIV (MWH) more frequently had cardiovascular (48% vs. 35%) and renal disease (22% vs. 15%). In multivariable models, frailty in WWH was independently associated with musculoskeletal disease (OR 3.85), cognitive impairment (OR 3.21), depressive symptoms (OR 2.67), and malnutrition (OR 2.14). In MWH, frailty was associated with musculoskeletal disease, cognitive impairment, malnutrition, and older age. Conclusions: Frailty exhibits gender-specific patterns: a multidimensional phenotype in WWH versus age-driven in MWH, supporting tailored, gender-responsive care integrating geriatric, mental, and musculoskeletal health.