Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort study

A substantial proportion of people with HIV (PWH) fail to achieve full immune recovery despite long-term antiretroviral therapy (ART), potentially increasing their risk of serious comorbidities. This study investigated the association between immune non-responder (INR) and the incidence of AIDS-defi...

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Main Authors: Xiaorui Li, Liqin Sun, Yun He, Fang Zhao, Yinsong Luo, Dian Zhao, Hui Wu, Jiayi He, Yuxin Jiang, Chenye Liu, Hongzhou Lu, Jiaye Liu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2025.2539198
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author Xiaorui Li
Liqin Sun
Yun He
Fang Zhao
Yinsong Luo
Dian Zhao
Hui Wu
Jiayi He
Yuxin Jiang
Chenye Liu
Hongzhou Lu
Jiaye Liu
author_facet Xiaorui Li
Liqin Sun
Yun He
Fang Zhao
Yinsong Luo
Dian Zhao
Hui Wu
Jiayi He
Yuxin Jiang
Chenye Liu
Hongzhou Lu
Jiaye Liu
author_sort Xiaorui Li
collection DOAJ
description A substantial proportion of people with HIV (PWH) fail to achieve full immune recovery despite long-term antiretroviral therapy (ART), potentially increasing their risk of serious comorbidities. This study investigated the association between immune non-responder (INR) and the incidence of AIDS-defining diseases (ADs) and non-AIDS-defining diseases (NADs) in a prospective cohort at the Third People's Hospital of Shenzhen, China. The low – and high-threshold cohorts included 7,874 and 8,077 individuals with baseline CD4+ T-cell counts < 350 and < 500cells/μL, respectively. INR was defined as failure to reach CD4+ T-cell thresholds (350 or 500 cells/μL) in two consecutive measurements during follow-up. Kaplan-Meier curves and Cox proportional hazards models were used to assess associations. Median follow-up after immune classification was 49.4 and 42.2 months in the low – and high-threshold cohorts, respectively. In the low-threshold cohort, INR was independently associated with significantly increased risks of ADs, including pneumocystis pneumonia (adjusted hazard ratio [aHR], 10.10; 95% confidence interval [CI]: 4.94–20.70), talaromycosis marneffei (aHR, 7.38; 95% CI: 3.51–15.50), and AIDs-defining cancers (aHR, 3.67; 95% CI: 1.20–11.20); and NADs, including end-stage liver disease (aHR, 15.00; 95% CI: 5.59–40.00), cardiovascular disease (aHR, 3.83; 95% CI: 2.14–6.87), chronic kidney disease (aHR, 1.78; 95% CI: 1.23–2.58), and non-AIDS-defining cancers (aHR, 4.75; 95% CI: 2.31–9.74). Similar associations were observed in the high-threshold cohort. INR is strongly associated with long-term morbidity in PWH. These findings highlight the need for improved risk assessment beyond CD4+ T-cell monitoring to reduce disease burden in PWH.
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spelling doaj-art-d5ff4237d07140908a52c33cfb62d8c12025-08-20T02:55:09ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2539198Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort studyXiaorui Li0Liqin Sun1Yun He2Fang Zhao3Yinsong Luo4Dian Zhao5Hui Wu6Jiayi He7Yuxin Jiang8Chenye Liu9Hongzhou Lu10Jiaye Liu11School of Public Health, Shenzhen University Medical School, Shenzhen, People’s Republic of ChinaDepartment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, People’s Republic of ChinaDepartment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, People’s Republic of ChinaDepartment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, People’s Republic of ChinaSchool of Public Health, Shenzhen University Medical School, Shenzhen, People’s Republic of ChinaSchool of Public Health, Shenzhen University Medical School, Shenzhen, People’s Republic of ChinaSchool of Public Health, Shenzhen University Medical School, Shenzhen, People’s Republic of ChinaSchool of Public Health, Shenzhen University Medical School, Shenzhen, People’s Republic of ChinaSchool of Public Health, Shenzhen University Medical School, Shenzhen, People’s Republic of ChinaSchool of Public Health, Shenzhen University Medical School, Shenzhen, People’s Republic of ChinaDepartment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, People’s Republic of ChinaSchool of Public Health, Shenzhen University Medical School, Shenzhen, People’s Republic of ChinaA substantial proportion of people with HIV (PWH) fail to achieve full immune recovery despite long-term antiretroviral therapy (ART), potentially increasing their risk of serious comorbidities. This study investigated the association between immune non-responder (INR) and the incidence of AIDS-defining diseases (ADs) and non-AIDS-defining diseases (NADs) in a prospective cohort at the Third People's Hospital of Shenzhen, China. The low – and high-threshold cohorts included 7,874 and 8,077 individuals with baseline CD4+ T-cell counts < 350 and < 500cells/μL, respectively. INR was defined as failure to reach CD4+ T-cell thresholds (350 or 500 cells/μL) in two consecutive measurements during follow-up. Kaplan-Meier curves and Cox proportional hazards models were used to assess associations. Median follow-up after immune classification was 49.4 and 42.2 months in the low – and high-threshold cohorts, respectively. In the low-threshold cohort, INR was independently associated with significantly increased risks of ADs, including pneumocystis pneumonia (adjusted hazard ratio [aHR], 10.10; 95% confidence interval [CI]: 4.94–20.70), talaromycosis marneffei (aHR, 7.38; 95% CI: 3.51–15.50), and AIDs-defining cancers (aHR, 3.67; 95% CI: 1.20–11.20); and NADs, including end-stage liver disease (aHR, 15.00; 95% CI: 5.59–40.00), cardiovascular disease (aHR, 3.83; 95% CI: 2.14–6.87), chronic kidney disease (aHR, 1.78; 95% CI: 1.23–2.58), and non-AIDS-defining cancers (aHR, 4.75; 95% CI: 2.31–9.74). Similar associations were observed in the high-threshold cohort. INR is strongly associated with long-term morbidity in PWH. These findings highlight the need for improved risk assessment beyond CD4+ T-cell monitoring to reduce disease burden in PWH.https://www.tandfonline.com/doi/10.1080/22221751.2025.2539198Immune non-responderAIDS-defining diseasesnon-AIDS-defining diseasesCD4+ T-cellmorbidity
spellingShingle Xiaorui Li
Liqin Sun
Yun He
Fang Zhao
Yinsong Luo
Dian Zhao
Hui Wu
Jiayi He
Yuxin Jiang
Chenye Liu
Hongzhou Lu
Jiaye Liu
Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort study
Emerging Microbes and Infections
Immune non-responder
AIDS-defining diseases
non-AIDS-defining diseases
CD4+ T-cell
morbidity
title Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort study
title_full Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort study
title_fullStr Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort study
title_full_unstemmed Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort study
title_short Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort study
title_sort two threshold defined immune non responders are associated with long term morbidity in people with hiv a prospective cohort study
topic Immune non-responder
AIDS-defining diseases
non-AIDS-defining diseases
CD4+ T-cell
morbidity
url https://www.tandfonline.com/doi/10.1080/22221751.2025.2539198
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