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Review
. 2023 Aug 7:14:1236460.
doi: 10.3389/fmicb.2023.1236460. eCollection 2023.

Recent advances in poor HIV immune reconstitution: what will the future look like?

Wenyuan Zhang  1 , Lianguo Ruan  1
Affiliations
Review

Recent advances in poor HIV immune reconstitution: what will the future look like?

Wenyuan Zhang et al. Front Microbiol. .

Abstract

Combination antiretroviral therapy has demonstrated proved effectiveness in suppressing viral replication and significantly recovering CD4+ T cell count in HIV type-1 (HIV-1)-infected patients, contributing to a dramatic reduction in AIDS morbidity and mortality. However, the factors affecting immune reconstitution are extremely complex. Demographic factors, co-infection, baseline CD4 cell level, abnormal immune activation, and cytokine dysregulation may all affect immune reconstitution. According to report, 10-40% of HIV-1-infected patients fail to restore the normalization of CD4+ T cell count and function. They are referred to as immunological non-responders (INRs) who fail to achieve complete immune reconstitution and have a higher mortality rate and higher risk of developing other non-AIDS diseases compared with those who achieve complete immune reconstitution. Heretofore, the mechanisms underlying incomplete immune reconstitution in HIV remain elusive, and INRs are not effectively treated or mitigated. This review discusses the recent progress of mechanisms and factors responsible for incomplete immune reconstitution in AIDS and summarizes the corresponding therapeutic strategies according to different mechanisms to improve the individual therapy.

Keywords: CD4+ T cells; HIV-1 infection; immune reconstitution; immunological non-responders; therapeutic interventions.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Potential risk factors for incomplete immune reconstitution. Including general characteristics (e.g., age, gender, CD4+ T-cell counts, body mass index (BMI) and the underlying diseases), metabolic and genetic factors also be confirmed can make some difference in immune recovery between different people living with HIV (PLHIV). Furthermore, coinfections with other virus, poor adherence and the regimens which with severe side effects also can interfere the immune restore. Factors that contribute to the reduction and destruction of CD4+ T cells also affect immune reconstitution, including: reduced haematopoiesis of bone marrow, thymic insufficiency, replication of HIV reservoirs, alteration of CD4+ T cell subpopulations, gut microbial translocation, transport effects of extracellular vesicles, dysregulation of cytokine and, immune senescence.
Figure 2
Figure 2
Pathways contribute to poor immune reconstitution from the above factors.
Figure 3
Figure 3
Interventions for poor HIV immune reconstitution. The mechanisms of incomplete immune reconstitution in PLHIV have not yet been clarified. The current intervention strategies for recover the CD4+ T cells mainly through two methods, immunotherapy and gene therapy. Immunotherapy can use the cytokines, vaccines or antibodies to activate latent cells and enhancing immune killing capacity. Similarly, treatments of targeting the anti-HIV-1 gene could make target cells resistant to viral infection. Other treatments to modulate immune also have some effect, like the application of vitamin D and probiotics.
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