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Elevation and persistence of CD8 T-cells in HIV infection: the Achilles heel in the ART era

Wei Cao, Vikram Mehraj, Daniel E Kaufmann, Taisheng Li, Jean-Pierre Routy

Abstract


Introduction: HIV infection leads to a disturbed T-cell homeostasis, featured by a depletion of CD4 T-cells and a persistent elevation of CD8 T-cells over disease progression. Most effort of managing HIV infection has been focused on CD4 T-cell recovery, while changes in the CD8 compartment were relatively underappreciated in the past.

Methods: A comprehensive literature review of publications in English language was conducted using major electronic databases. Our search was focused on factors contributing to CD8 T-cell dynamics in HIV infection and following antiretroviral therapy (ART).

Discussion: Normalization of CD8 counts is seldom observed even with optimal CD4 recovery following long-term treatment. Initiation of ART in primary HIV infection leads to enhanced normalization of CD8 count compared with long-term ART initiated in chronic infection. Importantly, such CD8 elevation in treated HIV infection is associated with an increased risk of inflammatory non-AIDS-related clinical events independent of CD4 T-cell recovery. The mechanisms underlying CD8 persistence remain largely unknown, which may include bystander activation, exhaustion and immunosenescence of CD8 T-cells. The information provided herein will lead to a better understanding of factors associated with CD8 persistence and contribute to the development of strategies aiming at CD8 normalization.

Conclusions: Persistence of CD8 T-cell elevation in treated HIV-infected patients is associated with an increased risk of non-AIDS-related events. Now that advances in ART have led to decreased AIDS-related opportunistic diseases, more attention has been focused on reducing non-AIDS events and normalizing persistent CD8 T-cell elevation.

Keywords: HIV; antiretroviral therapy; CD8 T-cell persistence; bystander activation; T-cell exhaustion.

(Published: 3 March 2016)

Citation: Cao W et al. Journal of the International AIDS Society 2016, 19:20697

http://www.jiasociety.org/index.php/jias/article/view/20697 | http://dx.doi.org/10.7448/IAS.19.1.20697




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