Late Clinical Presentation Outweighs Viral Characteristics in Determining Immune Depletion at HIV Diagnosis: A Five-Year Retrospective Study

Background: Late presentation and poor immunovirological outcomes persist among people living with HIV (PLWH). The differential impact of HIV-1 subtypes on baseline disease presentation in antiretroviral therapy (ART)-naïve individuals remains incompletely characterized, particularly in regions dominated by unique recombinant forms. Methods: We conducted a retrospective cross-sectional study involving ART-naïve newly diagnosed PLWH at our hospital from January 2020 to October 2025. Immunological (CD4+, CD8+ T-cell counts, and CD4+/CD8+ ratios), biochemical [albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], virological (HIV-1 subtype, genotypic drug resistance), and clinical (admission type, age) parameters were analyzed. Multivariate linear regression identified factors independently associated with CD4+ T-cell count, CD4+/CD8+ ratio, and ALB level. Results: The study population comprised 762 ART-naïve newly diagnosed PLWH who were predominantly male (87.5%), older (median age 59), and presented with advanced immunosuppression (median CD4+ count 100 cells/µL). CRF07_BC was the dominant subtype (57.4%). Significant subtype-specific differences were observed: CRF01_AE infection was associated with the lowest CD4+ counts (median 54 cells/µL, p = 0.0004) and CD4+/CD8+ ratios (p = 0.0005). Inpatient status, indicating more severe presentation, was independently associated with significantly lower CD4+ counts (β = −36.91, p < 0.0001) and ALB levels (β = −7.358, p < 0.0001). Contrary to typical immune aging, patients aged ≥50 years had higher CD4+ counts at diagnosis (105.5 vs. 74 cells/µL, p = 0.0039). Genotypic drug resistance (22.2% prevalence) showed no independent association with baseline immunological status. Conclusions: Our findings reveal a distinct profile of late HIV presentation in a contemporary Chinese cohort, characterized by advanced age and the predominance of CRF07_BC. The independent association of inpatient status, rather than HIV-1 subtype or drug resistance, with severe immunosuppression and hypoalbuminemia highlights clinical presentation as the paramount indicator of baseline disease severity. The unexpected immunological advantage in older adults warrants further investigation.