{
  "abstract": "Background People living with HIV (PLWH) remain at increased risk of major cardiovascular events (MACEs). Whether conventional cardiovascular risk algorithms adequately capture HIV-related determinants in the contemporary antiretroviral therapy (ART) era remains debated. In particular, the widespread introduction of second-generation integrase strand transfer inhibitors (INSTIs) after 2015 has substantially modified treatment strategies, toxicity profiles, and long-term metabolic exposure. We aimed to identify independent predictors of MACEs in PLWH and to assess whether risk determinants differed before and after the modern INSTI-based ART era.Methods We conducted a retrospective matched case–control study including PLWH with MACEs and controls individually matched 1:1 for duration of HIV infection to ensure comparable cumulative exposure to HIV-related risk. Cardiovascular risk was assessed using the SCORE2/SCORE2-OP algorithm, as appropriate. Multivariable conditional logistic regression identified independent predictors. A pre-specified sensitivity analysis restricted to individuals with baseline after 2015 - corresponding to the widespread implementation of second-generation INSTI-based regimens - was performed to evaluate determinants in the modern ART era.Results Overall, 670 PLWH were included, 335 cases with MACEs and 335 matched controls. Among cases, events included myocardial infarction (n=241), ischemic stroke (n=80), and hemorrhagic stroke (n=14). Median age was 52 yrs, and 73% were male. Cases had significantly higher median SCORE2 compared with controls (7.1 vs 4.3, p<0.005). However, 60% of MACEs occurred in individuals with SCORE2 <10%, indicating potential underestimation by conventional algorithms.In multivariable conditional logistic regression, HCV seropositivity (OR 6.55, 95% CI 1.52–28.31, p=0.012), cumulative ART exposure (OR 2.16, 95% CI 1.39–3.37, p<0.005), and ART polytherapy (OR 2.83, 95% CI 1.03–7.82, p=0.044) were independently associated with MACEs.The post-2015 subgroup included 262 PLWH (131 cases and 131 matched controls). In this modern ART-era population, HCV seropositivity was no longer significantly associated with MACEs (OR 2.01, p=0.321). Conversely, cumulative ART exposure (OR 2.31, 95% CI 1.10–4.88, p=0.028) and polytherapy (OR 8.18, 95% CI 2.20–30.39, p=0.002) remained independently associated with events. Lower HDL-c also emerged as a significant predictor (OR 0.92 per mg/dL increase, 95% CI 0.85–0.99, p=0.045).Conclusions In PLWH, cardiovascular risk appears partially underestimated by standard algorithms. While HCV coinfection was associated with MACEs in the overall cohort, its impact attenuated after 2015, possibly reflecting the effect of DAA-mediated HCV eradication. Conversely, cumulative treatment exposure and metabolic alterations emerged as key determinants in the modern ART era, suggesting an evolution of cardiovascular risk drivers in contemporary HIV care.Abstract OC63 Table 1Baseline characteristics of PLWH with major cardiovascular events (cases) and matched controls",
  "authors": [
    {
      "affiliations": [
        "Dipartimento di Scienze Mediche e Chirurgiche, UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy",
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "PF Salvo"
    },
    {
      "affiliations": [
        "Dipartimento di Scienze Mediche e Chirurgiche, UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy",
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "F Lombardi"
    },
    {
      "affiliations": [
        "Dipartimento di Scienze Mediche e Chirurgiche, UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy",
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "A Carbone"
    },
    {
      "affiliations": [
        "Dipartimento di Scienze Mediche e Chirurgiche, UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy",
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "G Baldin"
    },
    {
      "affiliations": [
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "G Lenzi"
    },
    {
      "affiliations": [
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "C De Vivo"
    },
    {
      "affiliations": [
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "S Colaiuda"
    },
    {
      "affiliations": [
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "F La Fata"
    },
    {
      "affiliations": [
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "G Cucinotta"
    },
    {
      "affiliations": [
        "Dipartimento di Scienze Mediche e Chirurgiche, UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy",
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "C Torti"
    },
    {
      "affiliations": [
        "Dipartimento di Scienze Mediche e Chirurgiche, UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy",
        "Dipartimento di Sicurezza e Bioetica, sezione Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy"
      ],
      "name": "S Di Giambenedetto"
    }
  ],
  "title": "OC63 Independent predictors of major cardiovascular events (MACEs) in people living with HIV (PLWH) before and after 2015: a matched case–control analysis",
  "uid": "a3d3c564-4d49-519b-bc69-18897e4f8b6c"
}