In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 8 ( 2021-8-27), p. e1009825-
Abstract:
Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir during ART by studying virologically-suppressed immunologic responders (IR, achieving a CD4 cell count 〉 500 cells/μL on or before two years after ART initiation), and virologically-suppressed suboptimal responders (ISR, did not achieve a CD4 cell count 〉 500 cells/μL in the first two years after ART initiation). Compared to IR, ISR demonstrated higher levels of HIV-DNA in naïve, central (CM), transitional (TM), and effector (EM) memory CD4 T-cells in blood, both pre- and on-ART, and specifically in CM CD4 T-cells in LN on-ART. Furthermore, ISR had higher pre-ART plasma levels of IL-7 and IL-15, cytokines regulating T-cell homeostasis. Notably, pre-ART PD-1 and TIGIT expression levels were higher in blood CM and TM CD4 T-cells for ISR; this was associated with a significantly lower fold-changes in HIV-DNA levels between pre- and on-ART time points exclusively on CM and TM T-cell subsets, but not naïve or EM T-cells. Finally, the frequency of CM CD4 T-cells expressing PD-1 or TIGIT pre-ART as well as plasma levels of IL-7 and IL-15 predicted HIV-DNA content on-ART. Our results establish the association between infection, T-cell homeostasis, and expression of PD-1 and TIGIT in long-lived CD4 T-cell subsets prior to ART with CD4 T-cell recovery and HIV persistence on-ART.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009825
DOI:
10.1371/journal.ppat.1009825.g001
DOI:
10.1371/journal.ppat.1009825.g002
DOI:
10.1371/journal.ppat.1009825.g003
DOI:
10.1371/journal.ppat.1009825.g004
DOI:
10.1371/journal.ppat.1009825.g005
DOI:
10.1371/journal.ppat.1009825.g006
DOI:
10.1371/journal.ppat.1009825.t001
DOI:
10.1371/journal.ppat.1009825.t002
DOI:
10.1371/journal.ppat.1009825.s001
DOI:
10.1371/journal.ppat.1009825.s002
DOI:
10.1371/journal.ppat.1009825.s003
DOI:
10.1371/journal.ppat.1009825.s004
DOI:
10.1371/journal.ppat.1009825.s005
DOI:
10.1371/journal.ppat.1009825.s006
DOI:
10.1371/journal.ppat.1009825.s007
DOI:
10.1371/journal.ppat.1009825.s008
DOI:
10.1371/journal.ppat.1009825.s009
DOI:
10.1371/journal.ppat.1009825.s010
DOI:
10.1371/journal.ppat.1009825.s011
DOI:
10.1371/journal.ppat.1009825.s012
DOI:
10.1371/journal.ppat.1009825.s013
DOI:
10.1371/journal.ppat.1009825.s014
DOI:
10.1371/journal.ppat.1009825.s015
DOI:
10.1371/journal.ppat.1009825.s016
DOI:
10.1371/journal.ppat.1009825.s017
DOI:
10.1371/journal.ppat.1009825.s018
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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