This is an observational, cross-sectional, comparative case–control, pilot study aimed at assessing the impact of HIV infection and age on immunological markers in people with HIV (PWH) on antiretroviral therapy (ART). The study included 40 PWH on ART, divided into two age groups (40–45 years vs. ≥60 years), and 30 HIV-uninfected controls matched by sex and age. The results show that older PWH on ART had more comorbidities and a higher frequency of CD8 T cells compared to older controls, with a significant decrease in CD8 naïve T cells with age. Additionally, younger PWH on ART exhibited higher frequencies of activated CD8 T cells and elevated levels of inflammatory markers (sCD14, IL-6) compared to age-matched controls, with values similar to those of older PWH on ART. These findings suggest that younger PWH on ART may experience accelerated immunoaging, highlighting the need for early interventions in this population.

Background: Comprehensive geriatric assessments (CGAs) are necessary to address the needs of people with human immunodeficiency virus infection (PWH) aged ≥ 50 years and ensure that they receive high-quality care. We aimed to identify the most effective tests from an extensive CGA to develop a short CGA. Methods: This observational, cross-sectional, and analytical study was conducted in three phases: (1) describing PWH aged ≥ 50 and matched controls; (2) jointly analyzing data to identify the most effective tests from the original CGA and develop a short version; and (3) applying the short CGA separately to both groups. Results: The most effective tests—the Lawton scale, SPPB, Barber questionnaire, Pittsburgh Sleep Quality Index, and Cognitive Complaints questionnaire—were used to create a short CGA. It identified abnormalities in 77% of PWH flagged by the full CGA, though 65% with the normal short CGA results had at least one abnormal result in the full version. Most false negatives were due to the excluded Hearing-Dependent Activities scale. Conclusions: These findings represent an initial step toward developing a short CGA for an easy and rapid identification of PWH aged ≥ 50, beyond a frailty assessment, who may benefit from early clinical management.

Long-acting (LA) antiretroviral therapies for human immunodeficiency virus (HIV), such as injectable formulations of cabotegravir and rilpivirine (CAB+RPV LA), are now available. Considering the limited data on the out-of-hospital administration of this combination, evaluating the implementation strategies needed is essential to support future clinical efforts. To gather data on barriers and facilitators of implementation for CAB+RPV LA in alternative outpatient facilities, this study used qualitative interviews informed by the Consolidated Framework for Implementation Research (CFIR), with 13 staff participating in the HOLA study (NCT06185452). Data analysis followed qualitative descriptive methods, assisted by Atlas.ti software version 22. The study adhered to the COREQ guidelines. Findings reveal five main factors to consider for implementation: operational and infrastructure adaptations, integrated management of human and organizational resources, need for coordination and follow-up, professional attitudes and work environment, and patient experience and patients’ needs perceived by professionals. This study emphasizes the comprehensive operational and infrastructure adaptations, adequate staff training, and supportive professional environment required for the successful implementation of CAB+RPV LA, while considering patients’ needs throughout the externalization process (trial registration number: NCT06643897).

Introduction The HOLA study is a 12-month randomised, hybrid implementation-effectiveness, phase IV, double-arm, open-label, multicentric study including virologically suppressed people living with HIV (PWH). HOLA, which started in September 2023, evaluates acceptability, appropriateness, feasibility and satisfaction of out-of-hospital administration of cabotegravir and rilpivirine long-acting (CAB+RPV LA). Methods A total of 110 PWH who are already under treatment with CAB+RPV LA or switch their antiretroviral therapy to CAB+RPV LA will be recruited from two main hospitals in Barcelona (Germans Trias I Pujol and Vall d’Hebrón) and Costa del Sol Hospital, in Marbella. The patients will be randomised 1:1 into a hospital group (administration of CAB+RPV LA in the hospital) and the outpatient group (out-of-hospital administration), including community or primary care centres. The main objectives of the study are to compare the acceptability at month 12 of the administration of CAB+RPV LA in and out-of-hospital centres from the perspective of patients, and assess and compare the safety and tolerability of CAB+RPV LA. The study takes place at nine clinical units in Catalonia and Andalusia (three tertiary hospitals (recruiting centres), one community centre, one sexually transmitted infection clinic and four primary care centres). Ethics and dissemination The current publication refers to V.3.0 of the protocol, with issue date 14 April 2024, as approved by the Comité de Ética de la Investigación con medicamentos del Hospital Universitari Germans Trias i Pujol (approval number AC-23-042-HGT-CEIM). The clinical trial will be conducted according to the principles of the Declaration of Helsinki, Fortaleza, Brazil, October 2013. This study will be conducted according to Spanish regulations regarding clinical trials (Royal Decree 1090/2015) and biomedical investigations (Organic Law 14/2007 of biomedical investigation and the Royal Decree 1716/2011), and the Clinical Trial Regulation (Regulation EU No 536/2014). Confidentiality requirements will follow the required Data Protection legislation. Enrolment completion in the study is expected by the end of May 2024, with an end of study expected in May 2025. Results emerging from this study will be reported in HIV national and international meetings as well as published in international journals with a high impact factor. If the outcome is deemed positive, we will also develop and propose policy guidelines for the integration of the administration of CAB+RPV LA in alternative outpatient facilities into the standard of care in the HIV care pathway. Trial registration number NCT06185452/EUCT number: 2023-503963-41-00.

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.

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.