Two-fold increased risk of cardiovascular events in people with MDR HIV: a matched cohort analysis with data from the PRESTIGIO registry
Authors: Clemente Tommaso , Diotallevi Sara , Minisci Davide , Di Biagio Antonio , Lolatto Riccardo , Attala Letizia , Cenderello Giovanni , Siribelli Alessia , Muccini Camilla , Lo Caputo Sergio , Tavio Marcello , Papaioannu Borjesson Rebecka , Giacomelli Andrea , Castagna Antonella , Spagnuolo Vincenzo ,   PRESTIGIO Study Group, Castagna Antonella , Spagnuolo Vincenzo , Armenia Daniele , Bonora Stefano , Calza Leonardo , Cattelan Anna Maria , Cenderello Giovanni , Cervo Adriana , Comi Laura , Di Biagio Antonio , Focà Emanuele , Gagliardini Roberta , Giacomelli Andrea , Lagi Filippo , Marchetti Giulia , Rusconi Stefano , Saladini Francesco , Santoro Maria Mercedes , Zazzi Maurizio , Galli Andrea , Armenia Daniele , Saladini Francesco , Santoro Maria Mercedes , Zazzi Maurizio , Carini Elisabetta , Bagaglio Sabrina , Piromall Girolamo , Lolatto Riccardo , Tavio Marcello , Paggi Alessandra Mataloni , Schioppa Ornella , Da Ros Valentina , Saracino Annalisa , Balena Flavia , Comi Laura , Valenti Daniela , Suardi Claudia , Viale Pierluigi , Calza Leonardo , Malerba Federica , Cretella Silvia , Riccardi Riccardo , Castelli Francesco , Focà Emanuele , Minisci Davide , Pennati Francesca , Menzaghi Barbara , Farinazzo Maddalena , Cacopardo Bruno , Celesia Maurizio , Raddusa Michele Salvatore Paternò , Giarratana Carmen , Fusco Paolo , Olivadese Vincenzo , Pan Angelo , Fornabaio Chiara , Brambilla Paola , Bartoloni Alessandro , Lagi Filippo , Corsi Paola , Kiros Seble Tekle , Ducci Filippo , Giachè Susanna , Costa Cecilia , Bellucci Alessio , Mirabelli Elisa , Santantonio Teresa , Lo Caputo Sergio , Ferrara Sergio , Narducci Arianna , Pontali Emanuele , Feasi Marcello , Sarà Antonio , Bassetti Matteo , Di Biagio Antonio , Blanchi Sabrina , Castagna Antonella , Spagnuolo Vincenzo , Muccini Camilla , Carini Elisabetta , Bagaglio Sabrina , Lolatto Riccardo , Galli Andrea , Borjesson Rebecka Papaioannu , Clemente Tommaso , Piromalli Girolamo , Antinori Spinello , Giacomelli Andrea , Formenti Tiziana , Schiavo Fabiola , Marchetti Giulia , Gazzola Lidia , Fineo Fabiana Trionfo , Puoti Massimo , Moioli Cristina , D’Amico Federico , Mussini Cristina , Cervo Adriana , Manzillo Elio , Lanzardo Amedeo , Cattelan Anna Maria , Mazzitelli Maria , Cascio Antonio , Trizzino Marcello , Fronti Elisa , Laccabue Diletta , Carli Federica , Gulminetti Roberto , Pagnucco Layla , Demitri Mattia , Francisci Daniela , De Socio Giuseppe , Schiaroli Elisabetta , Garlassi Elisa , Corsini Romina , Gagliardini Roberta , Fusto Marisa , Sarmati Loredana , Malagnino Vincenzo , Mulas Tiziana , Torti Mirko Compagno Carlo , Di Giambenedetto Simona , Lamonica Silvia , Salvo Pierluigi Francesco , Cenderello Giovanni , Pincino Rachele , Tumbarello Mario , Fabbiani Massimiliano , Panza Francesca , Rancan Ilaria , Di Perri Giovanni , Bonora Stefano , Ferrara Micol , Calcagno Andrea , Fantino Silvia , Nardi Stefano , Fiscon Marta 
Published: December 2024

Abstract

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 &lt; 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.