Format

Send to

Choose Destination
J Int AIDS Soc. 2016 Mar 3;19(1):20697. doi: 10.7448/IAS.19.1.20697. eCollection 2016.

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

Cao W1,2,3, Mehraj V1,2, Kaufmann DE4,5, Li T3, Routy JP1,2,6.

Author information

1
Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.
2
Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
3
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
4
Centre de recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
5
Department of Medicine, Université de Montréal, Montreal, QC, Canada.
6
Division of Hematology, McGill University Health Centre, Montreal, QC, Canada; jean-pierre.routy@mcgill.ca.

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:

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

PMID:
26945343
PMCID:
PMC4779330
DOI:
10.7448/IAS.19.1.20697
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center