An active HIV reservoir during ART is associated with maintenance of HIV-specific CD8+ T cell magnitude and short-lived differentiation status

Hiroshi Takata; Julie L. Mitchell; Julian Pacheco; Amélie Pagliuzza; Suteeraporn Pinyakorn; Supranee Buranapraditkun; Carlo Sacdalan; Louise Leyre; Sam Nathanson; Juyeon C. Kakazu; Jintana Intasan; Peeriya Prueksakaew; Nitiya Chomchey; Nittaya Phanuphak; Mark de Souza; Elias K. Haddad; Morgane Rolland; Sodsai Tovanabutra; Sandhya Vasan; Denise C. Hsu; Nicolas Chomont; Lydie Trautmann

doi:10.1016/j.chom.2023.08.012

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An active HIV reservoir during ART is associated with maintenance of HIV-specific CD8+ T cell magnitude and short-lived differentiation status

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An active HIV reservoir during ART is associated with maintenance of HIV-specific CD8+ T cell magnitude and short-lived differentiation status

Hiroshi Takata, Julie L. Mitchell, Julian Pacheco, Amélie Pagliuzza, Suteeraporn Pinyakorn, Supranee Buranapraditkun, Carlo Sacdalan, Louise Leyre, Sam Nathanson, Juyeon C. Kakazu, …

Cell host & microbe, v 31(9), pp 1494-1506

13 Sep 2023

DOI: https://doi.org/10.1016/j.chom.2023.08.012

PMID: 37708852

Featured in Collection : UN Sustainable Development Goals @ Drexel

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Abstract

antiretroviral therapy

CD8 T cells

HIV

HIV reservoir

Cell Differentiation

Before initiation of antiretroviral therapy (ART), HIV-specific CD8+ T cells are dysfunctional and short lived. To better understand the relationship between the HIV reservoir in CD4+ T cells and the magnitude and differentiation status of HIV-specific CD8+ T cells, we investigated these cells from acute and chronic HIV-infected individuals after 2 years of ART. Although both the HIV reservoir and the CD8+ T cell responses declined significantly after 2 years of ART, sustained HIV-specific CD8+ T cell responses correlated with a greater reduction of integrated HIV provirus. However, the magnitude of CD8+ T cells specific for HIV Gag, Pol, Nef, and Vif proteins positively associated with the active reservoir size during ART, measured as cell-associated RNA. Importantly, high HIV DNA levels strongly associate with maintenance of short-lived HIV-specific CD8+ T cells, regardless of ART initiation time. Our data suggest that the active reservoir maintains HIV-specific CD8+ T cell magnitude but prevents their differentiation into functional cells. • Magnitude of CD8+ T cell response associated with active HIV reservoir size on therapy•Sustained CD8+ T cell responses correlated with a greater HIV provirus decay • Residual HIV reservoir levels associated with maintenance of short-lived CD8+ T cells•Low HIV reservoir associated with generation of functional HIV-specific CD8+ T cells Takata et al. found that the residual antigen expression by the active HIV reservoir during suppressive antiretroviral therapy correlated with increased HIV-specific CD8+ T cell magnitude but prevented differentiation into functional cells. Thus, targeting the residual HIV reservoir may improve HIV-specific CD8+ T cell functionality needed for an HIV remission.

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Title: An active HIV reservoir during ART is associated with maintenance of HIV-specific CD8+ T cell magnitude and short-lived differentiation status
Creators: Hiroshi Takata - Oregon Health & Science University
Julie L. Mitchell - Oregon Health & Science University
Julian Pacheco - Oregon Health & Science University
Amélie Pagliuzza - Université de Montréal
Suteeraporn Pinyakorn - Walter Reed Army Institute of Research
Supranee Buranapraditkun - Chulalongkorn University
Carlo Sacdalan - Chulalongkorn University
Louise Leyre - Université de Montréal
Sam Nathanson - Oregon Health & Science University
Juyeon C. Kakazu - Walter Reed Army Institute of Research
Jintana Intasan - SEARCH Research Foundation (Thailand, Bangkok)
Peeriya Prueksakaew - SEARCH Research Foundation (Thailand, Bangkok)
Nitiya Chomchey - SEARCH Research Foundation (Thailand, Bangkok)
Nittaya Phanuphak - HIV Netherlands Australia Thailand Research Collaboration
Mark de Souza - SEARCH Research Foundation (Thailand, Bangkok)
Elias K. Haddad - Drexel University, Infectious Diseases (and HIV Medicine)
Morgane Rolland - Walter Reed Army Institute of Research
Sodsai Tovanabutra - U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Sandhya Vasan - Walter Reed Army Institute of Research
Denise C. Hsu - U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Nicolas Chomont - Université de Montréal
Lydie Trautmann - Walter Reed Army Institute of Research
Publication Details: Cell host & microbe, v 31(9), pp 1494-1506
Publisher: Elsevier
Resource Type: Journal article
Language: English
Academic Unit: Infectious Diseases (and HIV Medicine)
Web of Science ID: WOS:001078915000001
Scopus ID: 2-s2.0-85169932481
Other Identifier: 991021866805904721

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Web of Science research areas: Microbiology; Parasitology; Virology