{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:15:38Z","timestamp":1756858538666,"version":"3.44.0"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>CXCR4-tropic HIV seems to be associated with more clinical events than CCR5-tropic virus.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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\u2005years (IQR\u200a=\u200a5.80\u201310.6). Overall, 117 (81.3%) 4DR-PLWH experienced at least one clinical event during follow-up [incidence rate\u200a=\u200a32.5 (95% CI\u200a=\u200a29.3\u201335.9)]. 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\u200a=\u200a1.66 (95% CI\u200a=\u200a1.24\u20132.26), P\u200a&amp;lt;\u200a0.001] and persistent CXCR4-tropism [adjusted-incidence rate ratio: 2.01 (95% CI\u200a=\u200a1.04\u20133.91), P\u200a=\u200a0.037] were associated with the occurrence of HIV-related events.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               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