Previous Article in Journal
Unveiling the Mysteries of CLEC3B: Physiological Roles, Pathological Impacts, and Research Gaps
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Distinct Innate and Adaptive Immune Modules Differentially Associate with HIV Reservoir Size and Decay During Early Antiretroviral Therapy

1
Medical School of Chinese People’s Liberation Army (PLA), Beijing 100853, China
2
Senior Department of Infectious Diseases, Chinese PLA General Hospital, Beijing 100039, China
3
Department of Immunology & Microbiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2026, 15(13), 1161; https://doi.org/10.3390/cells15131161 (registering DOI)
Submission received: 29 April 2026 / Revised: 11 June 2026 / Accepted: 23 June 2026 / Published: 25 June 2026
(This article belongs to the Topic The Pathogenesis and Treatment of Immune-Mediated Disease)

Abstract

HIV reservoir size and decay represent distinct dimensions of viral persistence, yet whether they are governed by shared or separable immunological mechanisms during early antiretroviral therapy (ART) remains unclear. In this study, we employed multiparameter flow cytometry and bulk RNA sequencing to analyze longitudinal immune profiles across 21 treatment-naïve people living with HIV before ART initiation and at 1 and 5 months thereafter. Our findings revealed an apparent dissociation between HIV-1 DNA levels and decay rates in peripheral blood, and the two indicators appear to be relatively independent dimensions of viral persistence. Specifically, lower HIV-1 DNA levels were associated with higher frequencies of cytotoxic and adaptive-like natural killer (NK) cell subsets, whereas faster HIV-1 DNA decay was linked to restored HIV-specific CD4+ and CD8+ T-cell responses during treatment. Notably, transcriptomic analyses uncovered divergent gene expression signatures related to B cell-associated immunity and type I interferon pathways, with individuals with higher HIV-1 DNA levels exhibiting elevated expression of immunoglobulin and interferon-stimulated genes, while faster decay correlated with enrichment of antiviral and complement-related genes. Collectively, these findings provide a preliminary characterization of immune correlates of peripheral blood total HIV-1 DNA dynamics in the early phase following ART initiation. This work offers potential immune clues for exploring the viral reservoir and generates testable hypotheses for validation in future large cohorts.
Keywords: HIV reservoir; antiretroviral therapy (ART); innate immunity; adaptive immunity; NK cells; HIV-specific T cells HIV reservoir; antiretroviral therapy (ART); innate immunity; adaptive immunity; NK cells; HIV-specific T cells

Share and Cite

MDPI and ACS Style

Li, W.-Z.; Huang, H.-H.; Wang, H.-F.; Li, X.; Zhou, M.-J.; Yang, Y.-X.; Wang, Y.-Y.; Zhu, M.-M.; Sun, Y.; Chen, S.-Y.; et al. Distinct Innate and Adaptive Immune Modules Differentially Associate with HIV Reservoir Size and Decay During Early Antiretroviral Therapy. Cells 2026, 15, 1161. https://doi.org/10.3390/cells15131161

AMA Style

Li W-Z, Huang H-H, Wang H-F, Li X, Zhou M-J, Yang Y-X, Wang Y-Y, Zhu M-M, Sun Y, Chen S-Y, et al. Distinct Innate and Adaptive Immune Modules Differentially Associate with HIV Reservoir Size and Decay During Early Antiretroviral Therapy. Cells. 2026; 15(13):1161. https://doi.org/10.3390/cells15131161

Chicago/Turabian Style

Li, Wei-Zhe, Hui-Huang Huang, Hui-Fang Wang, Xia Li, Ming-Ju Zhou, Yu-Xuan Yang, You-Yuan Wang, Meng-Meng Zhu, Ying Sun, Si-Yuan Chen, and et al. 2026. "Distinct Innate and Adaptive Immune Modules Differentially Associate with HIV Reservoir Size and Decay During Early Antiretroviral Therapy" Cells 15, no. 13: 1161. https://doi.org/10.3390/cells15131161

APA Style

Li, W.-Z., Huang, H.-H., Wang, H.-F., Li, X., Zhou, M.-J., Yang, Y.-X., Wang, Y.-Y., Zhu, M.-M., Sun, Y., Chen, S.-Y., Fan, X., Jiao, Y.-M., Song, J.-W., Xu, R.-N., Zhen, C., Shi, M., Zhang, C., & Wang, F.-S. (2026). Distinct Innate and Adaptive Immune Modules Differentially Associate with HIV Reservoir Size and Decay During Early Antiretroviral Therapy. Cells, 15(13), 1161. https://doi.org/10.3390/cells15131161

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Article metric data becomes available approximately 24 hours after publication online.
Back to TopTop