Abstract
In stark contrast to the rapid development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective human immunodeficiency virus (HIV) vaccine is still lacking. Furthermore, despite virologic suppression and CD4 T-cell count normalization with antiretroviral therapy (ART), people living with HIV (PLWH) still exhibit increased morbidity and mortality compared to the general population. Such differences in health outcomes are related to higher risk behaviors, but also to HIV-related immune activation and viral coinfections. Among these coinfections, cytomegalovirus (CMV) latent infection is a well-known inducer of long-term immune dysregulation. Cytomegalovirus contributes to the persistent immune activation in PLWH receiving ART by directly skewing immune response toward itself, and by increasing immune activation through modification of the gut microbiota and microbial translocation. In addition, through induction of immunosenescence, CMV has been associated with a decreased response to infections and vaccines. This review provides a comprehensive overview of the influence of CMV on the immune system, the mechanisms underlying a reduced response to vaccines, and discuss new therapeutic advances targeting CMV that could be used to improve vaccine response in PLWH.
Highlights
The development of antiretroviral therapy (ART) against human immunodeficiency virus (HIV) has dramatically transformed the lives of people living with HIV (PLWH) and turned a life-threatening infection into a manageable, yet chronic, disease [1]
An optimal immune response to HIV is limited by different factors that include: (1) the unequaled genetic diversity and mutation rate of HIV; (2) the ability to infect and repress the very cells that orchestrate immune response, the CD4 helper T-cells; (3) the ability of the virus to integrate in the host genome and evade the immune response; (4) the persistence of immune activation despite long-term ART; and (5) the influence of other chronic viral coinfections, like cytomegalovirus (CMV) that exacerbate HIV-induced immune dysregulation
We aim to provide a comprehensive review of mechanisms by which CMV shapes the whole immune system, notably through the enhancement of gut microbial translocation, which contributes to reduced vaccine responses in PLWH
Summary
The development of antiretroviral therapy (ART) against human immunodeficiency virus (HIV) has dramatically transformed the lives of people living with HIV (PLWH) and turned a life-threatening infection into a manageable, yet chronic, disease [1]. Every actor shaping the immune system should be studied in order to increase the likelihood of success for future HIV vaccines Those factors notably include CMV, a well-known modulator of the human immune response. Reports suggest that higher levels of anti-CMV specific IgG stress, force the immune system to adapt in order to restrain this replication and to prevent reflect frequent episodes of such reactivation events [16,17]. In PLWH, CMV seropositivity is almost universal and potentiates HIV-induced imshedding is frequently detected in the blood and the genital tract of PLWH, and has mune activation, further contributing to non-AIDS comorbidities. Asymptomatic CMV been associated with T-cell immune activation and a decreased CD4/CD8 T-cell ratio shedding is frequently detected in the blood and the genital tract of PLWH, and has been (Figure 1) [17,25].
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