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Review
. 2020 Apr;107(4):597-612.
doi: 10.1002/JLB.4MR1019-189R. Epub 2020 Jan 22.

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Xiaodong Yang  1   2 , Bin Su  1   2 , Xin Zhang  1   2 , Yan Liu  1   2 , Hao Wu  1   2 , Tong Zhang  1   2
Affiliations
Review

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Xiaodong Yang et al. J Leukoc Biol. 2020 Apr.

Abstract

The morbidity and mortality of HIV type-1 (HIV-1)-related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy, which induces persistent suppression of HIV-1 replication and gradual recovery of CD4+ T-cell counts. However, ∼10-40% of HIV-1-infected individuals fail to achieve normalization of CD4+ T-cell counts despite persistent virological suppression. These patients are referred to as "inadequate immunological responders," "immunodiscordant responders," or "immunological non-responders (INRs)" who show severe immunological dysfunction. Indeed, INRs are at an increased risk of clinical progression to AIDS and non-AIDS events and present higher rates of mortality than HIV-1-infected individuals with adequate immune reconstitution. To date, the underlying mechanism of incomplete immune reconstitution in HIV-1-infected patients has not been fully elucidated. In light of this limitation, it is of substantial practical significance to deeply understand the mechanism of immune reconstitution and design effective individualized treatment strategies. Therefore, in this review, we aim to highlight the mechanism and risk factors of incomplete immune reconstitution and strategies to intervene.

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

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Factors associated with immunological non‐responders. Current understanding of the mechanism of incomplete immune reconstitution. INRs show severe immune dysfunction, including reduced production of progenitor cells in the bone marrow; thymic dysfunction; reduced CD34+ hematopoietic progenitor cells; abnormal immune activation; immune exhaustion; immunoregulatory cell imbalance, such as Treg and Th17 cells; increased immune‐senescence and cell apoptosis/pyroptosis, lymphoid tissue fibrosis, and microbial translocation; and persistent viral replication due to the HIV reservoir, and so on. Arrows in red highlight the maturation route of CD4+ T cells, while arrows in black indicate the factors associated with incomplete immune reconstitution. Th: helper T cell; Treg: regulatory T cell; NK: natural killer
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