Temporal Changes in Cardiovascular Risk Burden and Preventive Interventions by Sex and Menopausal Status in People Living with HIV.

Background and objectives:People with HIV (PWH) face excess cardiovascular (CV) risk driven by HIV-related factors and antiretroviral therapy (ART). Sex-based differences in CV risk profile and management have been reported, but their longitudinal evolution and the role of menopausal transition remain poorly characterized. This study assessed sex-based differences in CV risk factors, preventive measures, and cardiometabolic-kidney-metabolic (CKM) burden across three predefined periods (2005–2015, 2016–2020, 2021–2026), and evaluated the contribution of menopausal status in women living with HIV (WLHIV). Methods:We conducted a longitudinal observational study including ART-experienced PWH attending the Modena HIV Metabolic Clinic between 2005 and 2026. At each annual visit, participants underwent comprehensive assessment of HIV-related, endocrinological, and immuno-metabolic parameters, lifestyle factors, physical performance, transient elastography, and body composition (DEXA). Primary outcomes were sex-specific prevalence of CV risk factors (smoking, abacavir/protease inhibitor use, hypertension, diabetes) and preventive measures (statin use, LDL-C target attainment, antihypertensive therapy, ART modification). CKM burden was staged 0–4. WLHIV were additionally stratified by menopausal status. Results:At last available observation, among 5,474 PWH (1,785 women, 3,689 men), women had lower rates of hypertension (35.8% vs 49.2%), diabetes (6.0% vs 11.0%), and cardiovascular disease (4.2% vs 8.3%), but higher PI use (34.9% vs 30.6%) and physical inactivity (58.3% vs 47.9%) (all p<0.001). Despite similar dyslipidaemia prevalence (~80%), women were significantly less likely to receive statins (20.3% vs 29.0%, p<0.001). Time-to-event analysis showed that women were significantly less likely to initiate statins when indicated by LDL ≥100 mg/dL (HR 0.67, 95%CI 0.59–0.76, p<0.001) or dyslipidaemia diagnosis (HR 0.67, 95%CI 0.59–0.76, p<0.001), with a median time to initiation of 16.1 vs 10.6 years; no sex difference was observed when indication was SCORE-2 ≥5% (HR 1.14, p=0.24). Across time periods, uptake of ≥3 preventive measures improved in both sexes but remained lower in women (63.0% vs 70.4% in 2021–2026). CKM staging showed men progressed more rapidly to advanced stages (3–4: 36.9% in 2005–2015 to 61.3% in 2021–2026), while women, starting from a lower burden (18.5%), showed a steep increase to 47.1% in 2021–2026, progressively narrowing the sex gap. Conclusions:WLHIV showed persistent under-prescription of statins despite equivalent dyslipidaemia burden, a gap not explained by CV risk scores alone. While men progress faster to advanced CKM stages, women are rapidly catching up. Sex-tailored prevention strategies and systematic evaluation of menopausal transition are warranted.