Association between systemic inflammatory markers and CD4 T-cell count in people living with HIV: a cross-sectional study
Abstract
BackgroundPeople 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.MethodsThis 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).ResultsIn 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.ConclusionNLR, 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.
Related
- Joint association of cytokine gene variants and circulating inflammatory markers with increased breast cancer risk
- Systemic Inflammatory Indices and Hearing Loss in U.S. Adults Aged 40-85 Years: A Serial Cross-Sectional Study 1999-2020.
- Monocyte Dll4 Contributes to Systemic Inflammation in People Living With HIV
- New N -Pyridinyl(methyl)-N1-substituted-3-indolepropanamides Acting as Topical and Systemic Anti-inflammatory Agents
- Effects of β-Glucans on Pro-Inflammatory Markers and Behavioral Phenotype in a Valproic Acid (VPA)-Induced Autism Model in Zebrafish
BibTeX
@article{wen2026association,
title = {{Association between systemic inflammatory markers and CD4 T-cell count in people living with HIV: a cross-sectional study}},
author = {Jingli Wen and Zhenjiang Zhang and Zuoling Tang and Yining Yuan and Youde Yan and Huichun Ji},
journal = {Frontiers in Microbiology},
year = {2026},
month = nov,
doi = {10.3389/fmicb.2026.1979679},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1979679},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association between systemic inflammatory markers and CD4 T-cell count in people living with HIV: a cross-sectional study
AU - Jingli Wen
AU - Zhenjiang Zhang
AU - Zuoling Tang
AU - Yining Yuan
AU - Youde Yan
AU - Huichun Ji
PY - 2026
DA - 2026/11/05
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1979679
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1979679
AB - BackgroundPeople 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.MethodsThis 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).ResultsIn 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.ConclusionNLR, 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.
SN - 1664-302X
ER -