The Journal of antimicrobial chemotherapy · 2025
Persistence of CXCR4-tropic virus in people living with four-class drug-resistant HIV and its clinical impact in the modern antiretroviral era.
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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, PRESTIGIO Study Group
Аннотация
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.
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.