Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection.

Abstract

The timing and location of the establishment of the viral reservoir during acute HIV infection remain unclear. Using longitudinal blood and tissue samples obtained from HIV-infected individuals at the earliest stage of infection, we demonstrate that frequencies of infected cells reach maximal values in gut-associated lymphoid tissue and lymph nodes as early as Fiebig stage II, before seroconversion. Both tissues displayed higher frequencies of infected cells than blood until Fiebig stage III, after which infected cells were equally distributed in all compartments examined. Initiation of antiretroviral therapy (ART) at Fiebig stages I to III led to a profound decrease in the frequency of infected cells to nearly undetectable level in all compartments. The rare infected cells that persisted were preferentially found in the lymphoid tissues. Initiation of ART at later stages (Fiebig stages IV/V and chronic infection) induced only a modest reduction in the frequency of infected cells. Quantification of HIV DNA in memory CD4+ T cell subsets confirmed the unstable nature of most of the infected cells at Fiebig stages I to III and the emergence of persistently infected cells during the transition to Fiebig stage IV. Our results indicate that although a large pool of cells is infected during acute HIV infection, most of these early targets are rapidly cleared upon ART initiation. Therefore, infected cells present after peak viremia have a greater ability to persist.

• Authors: Louise Leyre, Eugène Kroon, Claire Vandergeeten, Carlo Sacdalan, Donn J Colby, Supranee Buranapraditkun, Alexandra Schuetz, Nitiya Chomchey, Mark de Souza, Wendy Bakeman, Rémi Fromentin, Suteeraporn Pinyakorn, Siriwat Akapirat, Rapee Trichavaroj, Suthat Chottanapund, Sopark Manasnayakorn, Rungsun Rerknimitr, Phandee Wattanaboonyoungcharoen, Jerome H Kim, Sodsai Tovanabutra, Timothy W Schacker, Robert O'Connell, Victor G Valcour, Praphan Phanuphak, Merlin L Robb, Nelson Michael, Lydie Trautmann, Nittaya Phanuphak, Jintanat Ananworanich, Nicolas Chomont, RV254/SEARCH010, RV304/SEARCH013, SEARCH011 study groups
• Journal: Science translational medicine (Sci Transl Med) Vol. 12 Issue 533 (03 04 2020) ISSN: 1946-6242 [Electronic] United States
• PMID: 32132218 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Topics

• CD4-Positive T-Lymphocytes
• HIV Infections (drug therapy)
• Humans
• T-Lymphocyte Subsets
• Viral Load
• Viremia (drug therapy)