Immune reconstitution and long-term survival outcomes in LTHIs and TPs living with long-term ART: a propensity score-matched cohort study in Xinjiang, China.

BACKGROUND: To compare immune reconstitution and long-term survival outcomes between long-term HIV-1 infected individuals (LTHIs) and typical progressors (TPs) under long-term antiretroviral therapy (ART) using a prospective HIV cohort in Yining City, China, and to provide evidence for risk stratification and follow-up management in long-term HIV care. METHODS: The study included eligible people living with HIV (PLWH) from a prospective cohort in Yining City, China, with the observation period ending on 1 April 2024. Immune reconstitution (IR) was defined as the most recent CD4+ T-cell count ≥350 cells/μL before the data cut-off. Propensity score matching (PSM) was used to balance baseline differences between groups. Poisson regression with robust variance was applied to estimate relative risks (RR) and 95% confidence intervals (95% CI) for IR, and absolute risk differences (RD) were also calculated. Stratified analyses were performed by sex and age. Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models were used to compare all-cause mortality. RESULTS: A total of 4,844 PLWH were included, comprising 2,788 LTHIs and 2,056 TPs. After PSM, 1,799 matched pairs were obtained. In the matched cohort, IR was achieved in 76.9% (1,384/1799) of LTHIs and 35.9% (646/1799) of TPs. LTHIs had a markedly higher probability of IR, with an absolute risk difference of 41.0% and an adjusted RR of 2.04 (95% CI: 1.92-2.17; p < 0.001). Stratified analyses showed generally consistent findings across sex and age subgroups. For time-to-event analyses, 1,292 LTHIs and 1,757 TPs had valid post-classification follow-up time. During follow-up, 140 deaths occurred among LTHIs and 557 among TPs. Kaplan-Meier curves showed significantly better cumulative survival in LTHIs than in TPs (log-rank p < 0.001). In the adjusted Cox model, LTHIs had a significantly lower risk of all-cause mortality than TPs (adjusted HR = 0.50, 95% CI: 0.41-0.60; p < 0.001). CONCLUSION: Even under long-term ART, LTHIs showed a higher probability of immune reconstitution and lower post-classification all-cause mortality compared with TPs. These findings suggest that the initial disease progression pattern was independently associated with immune reconstitution and post-classification mortality risk, and may help inform risk stratification in long-term HIV care.