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

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.