Immune reconstitution efficacy and associated risk factors for immunological non-response in people living with HIV during long-term antiretroviral therapy: a single-center retrospective cohort study at a tertiary care hospital in China

Despite sustained virological suppression under antiretroviral therapy (ART), a substantial proportion of people living with HIV (PLWH) fail to achieve adequate immune reconstitution. However, long-term real-world evidence characterizing immune recovery trajectories and determinants of immunological non-response (INR) has not yet been fully characterized, particularly in Asian populations. In this retrospective cohort study, we analyzed longitudinal immunological data from 8,637 PLWH who initiated ART between 2005 and 2019 at a large HIV treatment center in China and achieved sustained viral suppression. CD4 counts, CD8 counts, and CD4/CD8 ratios were assessed longitudinally to characterize immune reconstitution patterns, and Kaplan–Meier analyses and logistic regression models were used to evaluate factors associated with immune recovery and INR. We observed a biphasic pattern of immune reconstitution, with rapid early increases in CD4 counts and CD4/CD8 ratios followed by slower, sustained improvements over long-term ART. Nevertheless, normalization of the CD4/CD8 ratio occurred less frequently than CD4 count recovery, indicating persistent immune dysregulation in a subset of patients despite virological control. Lower baseline CD4 count and older age were the strongest predictors of incomplete immune reconstitution, with individuals initiating ART at advanced stages of immunodeficiency showing markedly reduced probability and slower tempo of immune normalization. These findings highlight the heterogeneity of immune recovery under long-term ART and underscore the importance of incorporating baseline immune status and age into risk stratification strategies. Longitudinal assessment of both CD4 counts and CD4/CD8 ratios may provide complementary insights into immune restoration and inform individualized monitoring and management of PLWH receiving ART.