Background CXCR4-tropic HIV seems to be associated with more clinical events than CCR5-tropic virus. Objectives This study aims to describe the effect of the persistence of CXCR4-tropic virus on the occurrence of clinical events in people with four-class drug-resistant HIV. Methods This is a retrospective study on people with four-class drug-resistant HIV from the PRESTIGIO Registry, with at least two HIV-tropism determinations during follow-up. Follow-up accrued from the date of the first four-class drug resistance evidence (baseline) until death, loss to follow-up or freezing date (31 December 2023). Univariable Poisson regression was used to estimate and compare incidence rates of clinical events. Predictors of clinical events were assessed by multivariable Poisson regression. Results A total of 144 people with four-class drug-resistant HIV [47 (33%) with persistent CXCR4-tropism, 39 (27%) with persistent CCR5-tropism and 58 (40%) with a tropism switch during follow-up] were included with a median follow-up of 7.80 years (IQR = 5.80-10.6). Overall, 117 (81.3%) 4DR-PLWH experienced at least one clinical event during follow-up [incidence rate = 32.5 (95% CI = 29.3-35.9)]. The persistence of CXCR4-tropic virus was associated with an increased risk of HIV-related events among people living with four-class drug-resistant HIV, even in modern ART era. After adjusting for age, sex at birth and CD4+/CD8+ at baseline, standardized viremia copy-years [adjusted-incidence rate ratio = 1.66 (95% CI = 1.24-2.26), P < 0.001] and persistent CXCR4-tropism [adjusted-incidence rate ratio: 2.01 (95% CI = 1.04-3.91), P = 0.037] were associated with the occurrence of HIV-related events. Conclusions Our findings confirm CXCR4-tropism as a marker of HIV progression also in the four-class drug-resistant population, suggesting the need of further prioritization of viro-immunological control and studies of pathogenic mechanisms in presence of CXCR4-tropic multidrug-resistant viral strains.
Persistence of CXCR4-tropic virus in people living with four-class drug-resistant HIV and its clinical impact in the modern antiretroviral era / Papaioannu Borjesson, Rebecka; Diotallevi, Sara; Lolatto, Riccardo; Cenderello, Giovanni; Comi, Laura; Cascio, Antonio; Saracino, Annalisa; Clemente, Tommaso; Mazzitelli, Maria; Lo Caputo, Sergio; Armenia, Daniele; Santoro, Maria Mercedes; Castagna, Antonella; Spagnuolo, Vincenzo; null, null; 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; Piromalli, 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; Papaioannu Borjesson, Rebecka; 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. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - STAMPA. - 80:(2025), pp. 2369-2374. [10.1093/jac/dkaf211]
Persistence of CXCR4-tropic virus in people living with four-class drug-resistant HIV and its clinical impact in the modern antiretroviral era
Lagi, Filippo;Bartoloni, Alessandro;Lagi, Filippo;Kiros, Seble Tekle;
2025
Abstract
Background CXCR4-tropic HIV seems to be associated with more clinical events than CCR5-tropic virus. Objectives This study aims to describe the effect of the persistence of CXCR4-tropic virus on the occurrence of clinical events in people with four-class drug-resistant HIV. Methods This is a retrospective study on people with four-class drug-resistant HIV from the PRESTIGIO Registry, with at least two HIV-tropism determinations during follow-up. Follow-up accrued from the date of the first four-class drug resistance evidence (baseline) until death, loss to follow-up or freezing date (31 December 2023). Univariable Poisson regression was used to estimate and compare incidence rates of clinical events. Predictors of clinical events were assessed by multivariable Poisson regression. Results A total of 144 people with four-class drug-resistant HIV [47 (33%) with persistent CXCR4-tropism, 39 (27%) with persistent CCR5-tropism and 58 (40%) with a tropism switch during follow-up] were included with a median follow-up of 7.80 years (IQR = 5.80-10.6). Overall, 117 (81.3%) 4DR-PLWH experienced at least one clinical event during follow-up [incidence rate = 32.5 (95% CI = 29.3-35.9)]. The persistence of CXCR4-tropic virus was associated with an increased risk of HIV-related events among people living with four-class drug-resistant HIV, even in modern ART era. After adjusting for age, sex at birth and CD4+/CD8+ at baseline, standardized viremia copy-years [adjusted-incidence rate ratio = 1.66 (95% CI = 1.24-2.26), P < 0.001] and persistent CXCR4-tropism [adjusted-incidence rate ratio: 2.01 (95% CI = 1.04-3.91), P = 0.037] were associated with the occurrence of HIV-related events. Conclusions Our findings confirm CXCR4-tropism as a marker of HIV progression also in the four-class drug-resistant population, suggesting the need of further prioritization of viro-immunological control and studies of pathogenic mechanisms in presence of CXCR4-tropic multidrug-resistant viral strains.
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