BACKGROUND: Major adverse cardiovascular events (MACEs) may contribute to the high morbidity in people with four-class drug-resistant HIV (4DR-PWH). OBJECTIVES: To explore the probability of MACEs in 4DR-PWH compared with non-4DR controls. METHODS: This was a retrospective, propensity score-matched cohort study on 4DR-PWH (cases) and non-4DR-PWH (controls), on ART, without previous MACEs. Controls were matched with cases in a 4:1 ratio for age, sex-assigned-at-birth and ART duration. Incidence rates (IRs) and incidence rate ratio (IRR) of MACEs with 95% CIs were modelled by Poisson regression. Cumulative probabilities of the first incident MACE were estimated by Kaplan-Meier curves. A multivariable stepwise Cox proportional hazards model estimated predictors of incident MACEs among covariates with univariable P <
0.100. RESULTS: Overall, 223 4DR-PWH and 797 non-4DR-PWH were evaluated. During a median (IQR) follow-up of 8.2 (5.4-11.1) years [1833 person-years of follow-up (PY)], 23/223 (10.3%) 4DR-PWH developed 29 MACEs, IR = 1.6 (95% CI = 1.1-2.3)/100 PY. During a median follow-up of 8.4 (5.2-11.0) years (6450 PY), 42/797 (5.3%) non-4DR controls had 45 MACEs, IR = 0.7 (95% CI = 0.5-0.9)/100 PY, IRR (4DR/non-4DR) = 2.3 (95% CI = 1.4-3.6). The cumulative probabilities of the first MACE were more than doubled in 4DR-PWH (P = 0.006). At multivariable analysis, an increased risk of MACEs was associated with 4DR status [adjusted hazard ratio (aHR) = 1.9
95% CI = 1.0-3.4], after adjusting for age, sex-assigned-at-birth, HIV load, CD4+ nadir, total cholesterol, HDL cholesterol, diabetes mellitus, statin use and baseline HCV serostatus. CONCLUSIONS: In PWH, MDR is significantly associated with a higher risk of cardiovascular events. Prompt implementation of prevention strategies is mandatory in this fragile population.