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 / Borjesson, R. P.; Diotallevi, S.; Lolatto, R.; Cenderello, G.; Comi, L.; Cascio, A.; Saracino, A.; Clemente, T.; Mazzitelli, M.; Lo Caputo, S.; Armenia, D.; Santoro, M. M.; Castagna, A.; Spagnuolo, V.; Castagna, A.; Spagnuolo, V.; Armenia, D.; Bonora, S.; Calza, L.; Cattelan, A. M.; Cenderello, G.; Cervo, A.; Comi, L.; Di Biagio, A.; Foca, E.; Gagliardini, R.; Giacomelli, A.; Lagi, F.; Marchetti, G.; Rusconi, S.; Saladini, F.; Santoro, M. M.; Zazzi, M.; Galli, A.; Armenia, D.; Saladini, F.; Santoro, M. M.; Zazzi, M.; Carini, E.; Bagaglio, S.; Piromalli, G.; Lolatto, R.; Tavio, M.; Paggi, A. M.; Schioppa, O.; Da Ros, V.; Saracino, A.; Balena, F.; Comi, L.; Valenti, D.; Suardi, C.; Viale, P.; Calza, L.; Malerba, F.; Cretella, S.; Riccardi, R.; Castelli, F.; Foca, E.; Minisci, D.; Pennati, F.; Menzaghi, B.; Farinazzo, M.; Cacopardo, B.; Celesia, M.; Raddusa, M. S. P.; Giarratana, C.; Fusco, P.; Olivadese, V.; Pan, A.; Fornabaio, C.; Brambilla, P.; Bartoloni, A.; Lagi, F.; Corsi, P.; Kiros, S. T.; Ducci, F.; Giache, S.; Costa, C.; Bellucci, A.; Mirabelli, E.; Santantonio, T.; Lo Caputo, S.; Ferrara, S.; Narducci, A.; Pontali, E.; Feasi, M.; Sara, A.; Bassetti, M.; Di Biagio, A.; Blanchi, S.; Castagna, A.; Spagnuolo, V.; Muccini, C.; Carini, E.; Bagaglio, S.; Lolatto, R.; Galli, A.; Papaioannu Borjesson, R.; Clemente, T.; Piromalli, G.; Antinori, S.; Giacomelli, A.; Formenti, T.; Schiavo, F.; Marchetti, G.; Gazzola, L.; Fineo, F. T.; Puoti, M.; Moioli, C.; D'Amico, F.; Mussini, C.; Cervo, A.; Manzillo, E.; Lanzardo, A.; Cattelan, A. M.; Mazzitelli, M.; Cascio, A.; Trizzino, M.; Fronti, E.; Laccabue, D.; Carli, F.; Gulminetti, R.; Pagnucco, L.; Demitri, M.; Francisci, D.; De Socio, G.; Schiaroli, E.; Garlassi, E.; Corsini, R.; Gagliardini, R.; Fusto, M.; Sarmati, L.; Malagnino, V.; Mulas, T.; Torti, M. C. C.; Di Giambenedetto, S.; Lamonica, S.; Salvo, P. F.; Cenderello, G.; Pincino, R.; Tumbarello, M.; Fabbiani, M.; Panza, F.; Rancan, I.; Di Perri, G.; Bonora, S.; Ferrara, M.; Calcagno, A.; Fantino, S.; Nardi, S.; Fiscon, M.. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 80:9(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
Clemente T.;Castagna A.;Spagnuolo V.;Castagna A.;Spagnuolo V.;Galli A.;Bagaglio S.;Castagna A.;Spagnuolo V.;Muccini C.;Bagaglio S.;Galli A.;Papaioannu Borjesson R.;Clemente T.;D'amico F.;Ferrara M.;Nardi S.;
2025-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
