Association between systemic inflammatory markers and CD4 T-cell count in people living with HIV: a cross-sectional study

Background People living with HIV (PLWH) experience persistent chronic inflammation even under effective antiretroviral therapy (ART) with viral suppression. The CD4 T-cell count remains the primary marker of immunodeficiency but does not capture the underlying inflammatory burden. Routine hematological inflammatory indices–including Absolute neutrophil count / Absolute lymphocyte count (NLR), Platelet count / Absolute lymphocyte count (PLR), (Absolute neutrophil count + Absolute monocyte count) / Absolute lymphocyte count (NMLR), (Neutrophil count × Monocyte count) / Lymphocyte count (SIRI), (Platelet count × Neutrophil count) / Lymphocyte count (SII)–have shown prognostic value in various diseases, yet their association with CD4 count in PLWH has not been systematically evaluated. Methods This single-center cross-sectional study enrolled 339 PLWH. Participants were categorized by CD4 count into binary (<500 vs. ≥500 cells/μL) and four-category (≥500, 350–500, 200–350, and <200 cells/μL) classifications. Multivariable logistic regression was used to assess associations between inflammatory markers (as continuous and tertile-categorized variables) and CD4 categories, calculating odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic splines evaluated non-linear relationships. Sensitivity analyses included standardized effect sizes, subgroup analysis in virologically suppressed patients, and multiple-testing corrections (Bonferroni and Benjamini–Hochberg). Results In adjusted binary models, higher NLR (OR = 1.79, 95% CI: 1.37–2.40, P < 0.001), PLR (OR = 1.01, 95% CI: 1.01–1.02, P < 0.001), and NMLR (OR = 1.77, 95% CI: 1.37–2.34, P < 0.001) were significantly associated with CD4 < 500 cells/μL, with significant dose-response trends (P for trend < 0.05). In four-category analyses, ORs progressively increased with worsening immunodeficiency, particularly for the < 200 cells/μL group. Restricted cubic splines showed no evidence of non-linearity for NLR, PLR, and NMLR (P for non-linearity all > 0.05), consistent with linear associations. SIRI showed only marginal association (OR = 1.46, P = 0.059), while SII was not significant. These associations remained robust in the virologically suppressed subgroup (87.9% with HIV RNA < 50 copies/mL) and survived Bonferroni and Benjamini–Hochberg corrections for multiple comparisons. Conclusion NLR, PLR, and NMLR are independently and linearly associated with lower CD4 T-cell counts in PLWH, with effect sizes increasing across worse immune strata. As these indices are derived from routine complete blood counts at no additional cost, they may serve as simple, accessible adjunctive biomarkers associated with lower CD4 T-cell counts, particularly in resource-limited settings. However, they should be regarded as indirect hematological indices rather than direct measures of systemic inflammatory burden; future studies incorporating established inflammatory biomarkers are needed to validate their clinical utility and prognostic value.