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

Cell host & microbe 2023 Sep 13

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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. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

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, RV254/SEARCH010, RV304/SEARCH013. An active HIV reservoir during ART is associated with maintenance of HIV-specific CD8+ T cell magnitude and short-lived differentiation status. Cell host & microbe. 2023 Sep 13;31(9):1494-1506.e4