HIV infection and immunosenescence: challenges and intervention strategies

Sep 30, 2026

Antiretroviral therapy has lengthened life expectancy for people with HIV, creating a rapidly growing ageing population worldwide, including in low- and middle-income settings. The reciprocal relationship between ageing and chronic HIV infection is strongly linked to immunosenescence, a progressive immune dysfunction marked by rising infection susceptibility. This accelerated immune ageing increases the long-term burden of age-related comorbidities and cancers.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Abstract

Background

Main body

Innate immune cell alterations

T and B cell changes and co-infection effects

Inflammation, mitochondrial damage, and lifestyle accelerants

Conclusion

Jin et al. BMC Medicine (2026) 24:8 [https://doi.org/10.1186/s12916-025-04545-6](https://doi.org/10.1186/s12916-025-04545-6) BMC Medicine REVIEW Open Access HIV infection and immunosenescence: challenges and intervention strategies Junyan Jin1,2†, Qianqian Xu1,2†, Xin Zhang1,2†, Aiwei Zhu1,2, Wei Xia1,2, Christiane Moog2,3*, Alex Siu Wing Chan4*, Tong Zhang1,2* and Bin Su1,2,5,6* Abstract Background Antiretroviral therapy has extended the life expectancy of people with HIV (PWH), leading to a rapidly expanding ageing population of PWH worldwide, including in low-and middle-income countries. The interaction between ageing and chronic HIV infection is closely associated with immunosenescence, and PWH are widely regarded as a model of accelerated immune ageing. Immunosenescence, characterized by a progressive decline in immune function and increased susceptibility to infections, contributes to a higher burden of age-related comorbidities and cancers, posing a major long-term health challenge for this population. Main body. The main focus of this review is on immunosenescence-related phenotypic and functional alterations in innate immune cells in PWH, including natural killer cells, monocytes, macrophages, and dendritic cells. It also outlines immunosenescence-related changes inT and B cells in the context of ageing and chronic HIV infection, such as thymic atrophy, loss of naïveT cell diversity, expansion of terminally differentiated and exhausted T-cell subsets, the impact of cytomegalovirus co-infection, and the emergence of age-associated B cells that impair humoral immunity and vaccine responsiveness. Furthermore, it discusses how persistent low-grade inflammation, mitochondrial damage induced by viral proteins and certain antiretroviral regimens, together with lifestyle factors such as cigarette smoking, accelerate systemic immune ageing, and summarizes emerging therapeutic and lifestyle strategies aimed at mitigating immunosenescence and improving long-term immune health, while noting that robust evidence remains limited. Conclusion Despite growing insights into HIV-associated immune ageing, there is still no universally applicable biomarker of immunosenescence. This gap underscores the need to develop robust, population-tailored biomarker panels and targeted interventions for PWH, to support integrated strategies that combine antiretroviral therapy with immune restoration and anti-ageing approaches, ultimately improving immune health and quality of life. Keywords HIV, Ageing, Immunosenescence, Immune cells †Junyan Jin, Qianqian Xu and Xin Zhang contributed equally to this work. *Correspondence: Christiane Moog [c.moog@unistra.fr](c.moog@unistra.fr)[ ](c.moog@unistra.fr)Alex Siu Wing Chan [alex_chan@hkbu.edu.hk](alex_chan@hkbu.edu.hk)[ ](alex_chan@hkbu.edu.hk)Tong Zhang [zt_doc@ccmu.edu.cn](zt_doc@ccmu.edu.cn)[ ](zt_doc@ccmu.edu.cn)Bin Su[binsu@ccmu.edu.cn](binsu@ccmu.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a co

FAQs

Why is immunosenescence particularly important in people with HIV?

Immunosenescence involves progressive immune decline and higher susceptibility to infections, contributing to age-related comorbidities and cancers in people with HIV.

Which immune cell populations does the review focus on?

The review emphasizes immunosenescence-related phenotypic and functional changes in innate immune cells, including natural killer cells, monocytes, macrophages, and dendritic cells.

Is there a universally applicable biomarker of immunosenescence for HIV?

No. The document states there is still no universally applicable biomarker and highlights the need for robust, population-tailored biomarker panels and targeted interventions.

Sep 30, 2026

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