Five-Year Immune Recovery After ART Initiation Among PLWH Aged ≥15 Years with Baseline Immunosuppression — China, 2013–2024

Introduction: Although antiretroviral therapy (ART) suppresses human immunodeficiency virus (HIV) replication in most people living with HIV (PLWH), 10%-40% show inadequate CD4 reconstitution despite sustained virologic suppression, increasing risks of AIDS-and non-AIDS-related events.Prior studies have suggested that immunological nonresponse (INR) is particularly common among individuals starting ART with immunosuppression.In China, real-world evidence for long-term immune recovery in immunosuppressed PLWH remains limited.Methods: Immunosuppression was defined as a baseline CD4<350 cells/µL at ART initiation.At year 5, INR was defined as CD4<350 cells/µL and favorable immune recovery as CD4 ≥500 cells/µL.From China's National ART Cohort, we included PLWH (aged ≥15 years; baseline CD4 <350 cells/µL) initiating ART during 2013-2019 who achieved year-5 virologic suppression (≤50 copies/mL).We described 5-year CD4 changes and examined factors associated with year-5 immune outcomes.Results: Among 315,109 participants, the median CD4 count increased from 199 cells/µL at baseline to 424 cells/µL over 5 years of ART.At year 5, 111,899 (35.5%) had CD4≥500 cells/µL (favorable immune recovery).In contrast, 109,344 (34.7%) patients had a CD4 <350 cells/µL and were classified as having INR.Lower baseline CD4 counts, older age, male sex, heterosexual or injection drug transmission, HBsAg positivity, anti-HCV positivity, and delayed ART initiation were associated with higher odds of INR.Compared to continuous non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy, continuous protease inhibitor (PI)-and integrase strand transfer inhibitor (INSTI)-based therapies, and switching from NNRTI-to INSTI-based regimens showed higher odds of favorable immune recovery.Conclusions: Among PLWH who initiated ART with immunosuppression and achieved virologic suppression at 5 years, most experienced immune recovery; however, approximately one-third remained INR.Early diagnosis, timely ART initiation, and targeted long-term immunological monitoring are required for populations at increased risk of suboptimal immune recovery.