Projected burden of hypertension-associated cardiovascular disease in people living with HIV versus HIV-negative adults in Eswatini.

Background: Having achieved the UNAIDS 95-95-95 targets, Eswatini faces a growing burden of non-communicable diseases which are major contributors to morbidity and mortality. Hypertension-associated cardiovascular disease (CVD) is rising among people living with HIV (PLHIV) as survival improves and metabolic risks - including those linked to dolutegravir (DTG) - increase. We projected CVD burden among PLHIV and HIV-negative adults (PLWHIV) through 2045 to inform integrated HIV-CVD planning. Methods: EMOD-HIV, an agent-based model calibrated to Eswatini's epidemic, generated HIV prevalence trajectories. These were combined with age-standardized Global Burden of Disease CVD estimates and published relative risks (RRs) to produce HIV-stratified CVD projections. CVD burden trajectories were then projected through 2045 using a logistic generalized additive model with Monte Carlo uncertainty quantification. Five scenarios were evaluated to assess how different assumptions about RR of CVD among PLHIV versus PLWHIV affect projected burden: (1) CVD prevalence under a constant RR; (2) CVD mortality under a constant RR; (3) HTN-attributable CVD mortality under a constant RR; (4) HTN-attributable CVD mortality under a post-DTG RR increase following Eswatini's 2021 dolutegravir rollout; and (5) HTN-attributable CVD mortality under a gradual RR increase from 2010-2045 reflecting cumulative metabolic and demographic shifts. Results: PLHIV consistently exhibited higher CVD burden than HIV-negative adults. Scenario 1: CVD prevalence was 11.0% (95% UI: 9.0-13.5%) among PLHIV versus 6.8% (6.0-7.8%) in 2025, stable through 2045. Scenario 2: CVD mortality rate was 0.60% (0.47-0.76%) versus 0.37% (0.31-0.45%) in 2025, declining modestly through 2045 with consistent excess. Scenario 3: HTN-attributable mortality was 73% (70-76%) versus 64% (61-66%) in women and 61% (58-64%) versus 58% (55-60%) in men, stable through 2045. Scenario 4: Following DTG rollout, mortality rose from 73% to 85% in women and 61% to 70% in men by 2022, remaining stable thereafter. Scenario 5: By 2045, mortality reached 85% (82-88%) in women and 67% (64-70%) in men with HIV, versus 60% (57 - 63%) and 55% (53 - 57%) in HIV-negative adults. Conclusions: While excess CVD burden among PLHIV is projected to persist even under stable risk conditions, ART-related metabolic trajectories - particularly those linked to DTG - may drive substantial widening of this gap through 2045. HTN-attributable CVD mortality is particularly elevated among women with HIV. Strengthening integrated HIV-NCD services, including blood pressure screening, risk-based therapy, and sex-specific DTG counseling, will be essential to sustain long-term health gains.