{"id":{"repo_id":"milano","oai_identifier":"oai:air.unimi.it:2434/1205035"},"canonical_url":"https://search.dev.ndltd.org/etd/milano/oai:air.unimi.it:2434/1205035","repository":{"repo_id":"milano","name":"Università degli Studi di Milano","base_url":"https://air.unimi.it/oai/request"},"display":{"title":"ULTRA-LOW LEVEL SOLUBLE P24 IS ASSOCIATED WITH INFLAMMATION IN PEOPLE WITH HIV ON LONG-TERM VIROLOGICALLY SUPPRESSIVE ANTIRETROVIRAL THERAPY","abstract":"Introduction: Despite virologically suppressive antiretroviral therapy (ART), residual inflammation persists in people with HIV (PWH), thus driving higher risk of serious non-AIDS events (SNAEs) and mortality. Circulating HIV proteins have been detected in some suppressed PWH, as an expression of the persistence of the translation-competent reservoir. We therefore seek to investigate whether peripheral inflammation and mortality risk are associated with p24 production in this population. Methods: PWH on suppressive ART and age/sex-matched healthy controls without HIV were enrolled. Ultra-low level serum p24 was cross-sectionally (baseline) and longitudinally (6 and 12 months) quantified by Simoa following immune complexes dissociation. In addition, the following were cross-sectionally measured at baseline: plasma biomarkers of inflammaging (Luminex/ELISA), CD38+CD8+ T-cells (flow cytometry), cell-associated total/unintegrated/integrated HIV DNA (qPCR). Mortality risk was estimated by VACS Index 2.0. In vitro experiments tested whether p24 modulates IP-10 secretion by PBMCs. Results: 120 PWH and 20 controls were recruited. PWH exhibited a distinct inflammaging profile characterised by elevated IP-10, TNF-α, IL-17A, IL-8, sCD14, sCD163, TIMP-1, and GDF-15 compared to controls. Several biomarkers were associated with the VACS Index 2.0 in univariable analyses, but only IP-10 and GDF-15 remained independently associated in multivariable modelling. Soluble p24 was detectable in 25/120 (20.8%) PWH at baseline (median: 0.0516 pg/mL; range: 0.0264–0.8280 pg/mL), and its detectability was associated with male sex yet not with immunological parameters or HIV DNA. Among inflammaging biomarkers, p24 was associated exclusively with higher plasma IP-10, both as categorical and continuous variable, even after adjustment for sex, age, CD4 T-cell count, and ART duration. Longitudinal analyses in a subset of 30 PWH revealed dynamic p24 patterns, with persistently p24-positive PWH exhibiting the highest baseline IP-10 levels. In vitro, p24 alone did not induce IP-10 secretion, but in the presence of IFN-γ and TNF-α, it produced a modest yet significant increase, supporting a context-dependent proinflammatory effect. Conclusions: These findings demonstrate that a subset (~21%) of virologically suppressed PWH produce detectable levels of soluble p24, and that this residual HIV protein expression is selectively associated with heightened IP-10–mediated inflammation. Given the positive association between IP-10 and VACS Index 2.0, a measure of physiologic frailty and risk of death, these data suggest that p24-driven inflammation may contribute to SNAEs and mortality in virologically suppressed PWH.","abstract_html":"Introduction: Despite virologically suppressive antiretroviral therapy (ART), residual inflammation persists in people with HIV (PWH), thus driving higher risk of serious non-AIDS events (SNAEs) and mortality. Circulating HIV proteins have been detected in some suppressed PWH, as an expression of the persistence of the translation-competent reservoir. We therefore seek to investigate whether peripheral inflammation and mortality risk are associated with p24 production in this population. Methods: PWH on suppressive ART and age/sex-matched healthy controls without HIV were enrolled. Ultra-low level serum p24 was cross-sectionally (baseline) and longitudinally (6 and 12 months) quantified by Simoa following immune complexes dissociation. In addition, the following were cross-sectionally measured at baseline: plasma biomarkers of inflammaging (Luminex/ELISA), CD38+CD8+ T-cells (flow cytometry), cell-associated total/unintegrated/integrated HIV DNA (qPCR). Mortality risk was estimated by VACS Index 2.0. In vitro experiments tested whether p24 modulates IP-10 secretion by PBMCs. Results: 120 PWH and 20 controls were recruited. PWH exhibited a distinct inflammaging profile characterised by elevated IP-10, TNF-α, IL-17A, IL-8, sCD14, sCD163, TIMP-1, and GDF-15 compared to controls. Several biomarkers were associated with the VACS Index 2.0 in univariable analyses, but only IP-10 and GDF-15 remained independently associated in multivariable modelling. Soluble p24 was detectable in 25/120 (20.8%) PWH at baseline (median: 0.0516 pg/mL; range: 0.0264–0.8280 pg/mL), and its detectability was associated with male sex yet not with immunological parameters or HIV DNA. Among inflammaging biomarkers, p24 was associated exclusively with higher plasma IP-10, both as categorical and continuous variable, even after adjustment for sex, age, CD4 T-cell count, and ART duration. Longitudinal analyses in a subset of 30 PWH revealed dynamic p24 patterns, with persistently p24-positive PWH exhibiting the highest baseline IP-10 levels. In vitro, p24 alone did not induce IP-10 secretion, but in the presence of IFN-γ and TNF-α, it produced a modest yet significant increase, supporting a context-dependent proinflammatory effect. Conclusions: These findings demonstrate that a subset (~21%) of virologically suppressed PWH produce detectable levels of soluble p24, and that this residual HIV protein expression is selectively associated with heightened IP-10–mediated inflammation. Given the positive association between IP-10 and VACS Index 2.0, a measure of physiologic frailty and risk of death, these data suggest that p24-driven inflammation may contribute to SNAEs and mortality in virologically suppressed PWH.","abstract_has_math":false,"creators":["AUGELLO, MATTEO"],"institution":"Università degli Studi di Milano","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["tutor: C. Tincati ; coordinatore: M. S. Clerici","M. Augello","TINCATI, CAMILLA","CLERICI, MARIO SALVATORE"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2026,"date_issued":"2026-01-22","date_published":"2026-01-22","updated_at":"2026-07-27T20:19:03Z","subjects":["Settore MEDS-10/B - Malattie infettive"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess","license:Creative commons","license uri:http://creativecommons.org/licenses/by-sa/4.0/"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2434/1205035","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["tutor: C. Tincati ; coordinatore: M. S. Clerici","M. Augello","TINCATI, CAMILLA","CLERICI, MARIO SALVATORE"]},{"key":"dc:creator","label":"Author","values":["AUGELLO, MATTEO"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2026-01-22"]},{"key":"dc:publisher","label":"Institution","values":["Università degli Studi di Milano"]},{"key":"dc:relation","label":"Dc Relation","values":["numberofpages:58"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Settore MEDS-10/B - Malattie infettive"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess","license:Creative commons","license uri:http://creativecommons.org/licenses/by-sa/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2434/1205035"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Introduction: Despite virologically suppressive antiretroviral therapy (ART), residual inflammation persists in people with HIV (PWH), thus driving higher risk of serious non-AIDS events (SNAEs) and mortality. Circulating HIV proteins have been detected in some suppressed PWH, as an expression of the persistence of the translation-competent reservoir. We therefore seek to investigate whether peripheral inflammation and mortality risk are associated with p24 production in this population. Methods: PWH on suppressive ART and age/sex-matched healthy controls without HIV were enrolled. Ultra-low level serum p24 was cross-sectionally (baseline) and longitudinally (6 and 12 months) quantified by Simoa following immune complexes dissociation. In addition, the following were cross-sectionally measured at baseline: plasma biomarkers of inflammaging (Luminex/ELISA), CD38+CD8+ T-cells (flow cytometry), cell-associated total/unintegrated/integrated HIV DNA (qPCR). Mortality risk was estimated by VACS Index 2.0. In vitro experiments tested whether p24 modulates IP-10 secretion by PBMCs. Results: 120 PWH and 20 controls were recruited. PWH exhibited a distinct inflammaging profile characterised by elevated IP-10, TNF-α, IL-17A, IL-8, sCD14, sCD163, TIMP-1, and GDF-15 compared to controls. Several biomarkers were associated with the VACS Index 2.0 in univariable analyses, but only IP-10 and GDF-15 remained independently associated in multivariable modelling. Soluble p24 was detectable in 25/120 (20.8%) PWH at baseline (median: 0.0516 pg/mL; range: 0.0264–0.8280 pg/mL), and its detectability was associated with male sex yet not with immunological parameters or HIV DNA. Among inflammaging biomarkers, p24 was associated exclusively with higher plasma IP-10, both as categorical and continuous variable, even after adjustment for sex, age, CD4 T-cell count, and ART duration. Longitudinal analyses in a subset of 30 PWH revealed dynamic p24 patterns, with persistently p24-positive PWH exhibiting the highest baseline IP-10 levels. In vitro, p24 alone did not induce IP-10 secretion, but in the presence of IFN-γ and TNF-α, it produced a modest yet significant increase, supporting a context-dependent proinflammatory effect. Conclusions: These findings demonstrate that a subset (~21%) of virologically suppressed PWH produce detectable levels of soluble p24, and that this residual HIV protein expression is selectively associated with heightened IP-10–mediated inflammation. Given the positive association between IP-10 and VACS Index 2.0, a measure of physiologic frailty and risk of death, these data suggest that p24-driven inflammation may contribute to SNAEs and mortality in virologically suppressed PWH."]},{"key":"dc:title","label":"Title","values":["ULTRA-LOW LEVEL SOLUBLE P24 IS ASSOCIATED WITH INFLAMMATION IN PEOPLE WITH HIV ON LONG-TERM VIROLOGICALLY SUPPRESSIVE ANTIRETROVIRAL THERAPY"]}]}],"canonical_facts":{"dc:contributor":["tutor: C. Tincati ; coordinatore: M. S. Clerici","M. Augello","TINCATI, CAMILLA","CLERICI, MARIO SALVATORE"],"dc:creator":["AUGELLO, MATTEO"],"dc:date":["2026-01-22"],"dc:description":["Introduction: Despite virologically suppressive antiretroviral therapy (ART), residual inflammation persists in people with HIV (PWH), thus driving higher risk of serious non-AIDS events (SNAEs) and mortality. Circulating HIV proteins have been detected in some suppressed PWH, as an expression of the persistence of the translation-competent reservoir. We therefore seek to investigate whether peripheral inflammation and mortality risk are associated with p24 production in this population. Methods: PWH on suppressive ART and age/sex-matched healthy controls without HIV were enrolled. Ultra-low level serum p24 was cross-sectionally (baseline) and longitudinally (6 and 12 months) quantified by Simoa following immune complexes dissociation. In addition, the following were cross-sectionally measured at baseline: plasma biomarkers of inflammaging (Luminex/ELISA), CD38+CD8+ T-cells (flow cytometry), cell-associated total/unintegrated/integrated HIV DNA (qPCR). Mortality risk was estimated by VACS Index 2.0. In vitro experiments tested whether p24 modulates IP-10 secretion by PBMCs. Results: 120 PWH and 20 controls were recruited. PWH exhibited a distinct inflammaging profile characterised by elevated IP-10, TNF-α, IL-17A, IL-8, sCD14, sCD163, TIMP-1, and GDF-15 compared to controls. Several biomarkers were associated with the VACS Index 2.0 in univariable analyses, but only IP-10 and GDF-15 remained independently associated in multivariable modelling. Soluble p24 was detectable in 25/120 (20.8%) PWH at baseline (median: 0.0516 pg/mL; range: 0.0264–0.8280 pg/mL), and its detectability was associated with male sex yet not with immunological parameters or HIV DNA. Among inflammaging biomarkers, p24 was associated exclusively with higher plasma IP-10, both as categorical and continuous variable, even after adjustment for sex, age, CD4 T-cell count, and ART duration. Longitudinal analyses in a subset of 30 PWH revealed dynamic p24 patterns, with persistently p24-positive PWH exhibiting the highest baseline IP-10 levels. In vitro, p24 alone did not induce IP-10 secretion, but in the presence of IFN-γ and TNF-α, it produced a modest yet significant increase, supporting a context-dependent proinflammatory effect. Conclusions: These findings demonstrate that a subset (~21%) of virologically suppressed PWH produce detectable levels of soluble p24, and that this residual HIV protein expression is selectively associated with heightened IP-10–mediated inflammation. Given the positive association between IP-10 and VACS Index 2.0, a measure of physiologic frailty and risk of death, these data suggest that p24-driven inflammation may contribute to SNAEs and mortality in virologically suppressed PWH."],"dc:identifier":["https://hdl.handle.net/2434/1205035"],"dc:language":["eng"],"dc:publisher":["Università degli Studi di Milano"],"dc:relation":["numberofpages:58"],"dc:rights":["info:eu-repo/semantics/openAccess","license:Creative commons","license uri:http://creativecommons.org/licenses/by-sa/4.0/"],"dc:subject":["Settore MEDS-10/B - Malattie infettive"],"dc:title":["ULTRA-LOW LEVEL SOLUBLE P24 IS ASSOCIATED WITH INFLAMMATION IN PEOPLE WITH HIV ON LONG-TERM VIROLOGICALLY SUPPRESSIVE ANTIRETROVIRAL THERAPY"],"dc:type":["info:eu-repo/semantics/doctoralThesis"]},"updated_at":"2026-07-27T20:19:03Z"}