Abstract
BACKGROUND: Human immunodeficiency virus (HIV) infection frequently leads to central nervous system (CNS) complications, especially as immunity declines. While antiretroviral therapy (ART) has transformed HIV into a manageable condition, in clinical practice, a significant subset of individuals still present with advanced immunosuppression (CD4 < 200 cells/μL) due to delayed diagnosis, treatment failure, or poor adherence, leading to AIDS-defining conditions. This study investigated how immune status affects CNS infection characteristics and outcomes specifically within this immunocompromised spectrum of AIDS individuals, aiming to provide refined evidence for risk stratification and early intervention in late-presenting or treatment-experienced individuals. METHODS: We retrospectively analyzed 213 individuals with AIDS who presented with CNS symptoms and confirmed CNS infections. They were grouped by CD4 count: 101 with ≥200 cells/μL (Moderate to High Immune, HI) and 112 with <200 cells/μL (Low Immune, LI). We compared symptoms, cerebrospinal fluid (CSF) findings, imaging results, detected pathogens, treatment outcomes, and quality of life between groups. RESULTS: Individuals with low CD4 counts showed significantly more severe symptoms like altered consciousness (50.00% vs. 31.68%, p = 0.007) and seizures (25.00% vs. 12.87%, p = 0.025). Their CSF tests revealed higher white blood cell counts (30.72 ± 8.50 vs. 18.32 ± 4.41 cells/μL, p < 0.001), higher protein levels (85.21 ± 32.14 vs. 62.36 ± 20.53 mg/dL, p < 0.001), lower glucose levels (41.35 ± 13.40 vs. 50.12 ± 10.24 mg/dL, p < 0.001), and higher pathogen detection rates (53.57% vs. 26.73%, p < 0.001). The CD4 < 200 group also had significantly lower CD4/CD8 ratios (p < 0.001). Brain magnetic resonance imaging (MRI) also revealed a higher prevalence of abnormalities in the LI group, including parenchymal lesions, ventriculomegaly, meningeal enhancement, and focal lesions (p < 0.05). Opportunistic infections, particularly Cryptococcus neoformans (49.11% vs. 22.77%, p < 0.001), Mycobacterium tuberculosis (MTB) (18.75% vs. 7.92%, p = 0.021), and Cytomegalovirus (CMV) (15.18% vs. 5.94%, p = 0.030), were much more common in the LI group. Individuals in the MHI group achieved complete remission more often (66.34% vs. 51.79%, p = 0.031) and had less disease progression (9.90% vs. 21.42%, p = 0.022). Their quality of life scores after treatment for the CNS infection were also significantly better across physical, psychological, social, and overall health domains (p < 0.05). Multivariate analysis confirmed that a higher CD4 count strongly protected against poor outcomes (OR = 0.321 per 100 cells/μL increase, p < 0.001). CONCLUSION: This study quantifies the severe impact of advanced immunosuppression (CD4 < 200 cells/μL) on CNS infection presentation, short-term treatment response (for CNS infections), and quality of life at discharge. Preventing immune decline below this threshold is critical.