Chinese HIV Controllers Exhibit Different Immunophenotypic Profiles and Viral Reservoir Dynamics Compared to Normal Progressors: A Real-World Cohort Study.

HIV controllers (HICs) maintain low-level viremia and normal CD4+ T-cell counts without antiviral therapy (ART). This study aimed to characterized immunophenotypic and reservoir dynamics in Chinese HICs, revealing key distinctions from normal progressors (NPs). This prospective single-center study enrolled HICs (ART-free HIV RNA < 2000 copies/mL ≥ 12 months) and age/sex-matched NPs served as controls at PUMCH (2000-2024). Longitudinal immunophenotyping of PBMCs was performed and used PCR to detected total HIV-1 DNA. Among 1792 PLWH, 46 (2.5%) HICs (median age 31 years, 69% male) were enrolled in this study underwent 6 (5-12.5) years follow-up, including 8 elite controllers and 38 viral controllers. Baseline CD4+ T-cell counts were 567 (507-757) cells/μL, VL 2.64 (2.35-2.98) log10 copies/mL. Compared with NPs, HICs exhibited higher NK-cell percentage, B-cell percentage, naive CD4+ T-cell counts and CD4/CD8 ratio, lower activated CD8+ T-cells (CD38+orHLA-DR+) percentage and total HIV-DNA at baseline (p < 0.05). ART reduced HIV-DNA in NPs but remained higher than HICs (p < 0.05). Five HICs discontinued follow-up, 43.9% (18/41) HICs lost virological control at 6 (5-9) years. HICs experiencing lost virological control exhibited elevated baseline HIV-DNA, activated CD8+ T-cells percentage and lower CD4/CD8 ratio. Preceding control loss, declining CD4+ T-cell counts (predominantly naive subsets), CD4/CD8 ratios and rising activated CD8+ T-cells percentage were observed. Conversely, HICs maintaining virological control retained stable CD38+CD8+ T-cell percentages, CD4/CD8 ratio and naive CD4+ T-cell counts exhibited increased elevated HLA-DR+CD8+ T-cell percentage. Chinese HICs exhibit different immunophenotypes with reduced HIV-DNA versus NPs. Longitudinal tracking of HIV-1 DNA, activated CD8+ T-cell, naïve CD4+ T-cell dynamics, and CD4/CD8 stability predict virologic failure in HICs.