Faculty Collaboration Database

Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART. PLoS Pathog 2021 Aug;17(8):e1009825

Date

08/28/2021

Pubmed ID

34449812

Pubmed Central ID

PMC8397407

DOI

10.1371/journal.ppat.1009825

Scopus ID

2-s2.0-85114118434 (requires institutional sign-in at Scopus site)   15 Citations

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.

Author List

Pino M, Pereira Ribeiro S, Pagliuzza A, Ghneim K, Khan A, Ryan E, Harper JL, King CT, Welbourn S, Micci L, Aldrete S, Delman KA, Stuart T, Lowe M, Brenchley JM, Derdeyn CA, Easley K, Sekaly RP, Chomont N, Paiardini M, Marconi VC

Author

Sol Del Mar Aldrete MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anti-Retroviral Agents
CD4-Positive T-Lymphocytes
Cytokines
DNA, Viral
Female
HIV Infections
HIV-1
Homeostasis
Humans
Immunologic Memory
Male
Middle Aged
T-Lymphocyte Subsets
Viral Load