Paradoxically Greater Persistence of HIV RNA-Positive Cells in Lymphoid Tissue When ART Is Initiated in the Earliest Stage of Infection

Author:

Kroon Eugène1,Chottanapund Suthat1,Buranapraditkun Supranee2,Sacdalan Carlo1,Colby Donn J134,Chomchey Nitiya1,Prueksakaew Peeriya1,Pinyakorn Suteeraporn34,Trichavaroj Rapee125,Vasan Sandhya23,Manasnayakorn Sopark6,Reilly Cavan7,Helgeson Erika7,Anderson Jodi8,David Caitlin9,Zulk Jacob8,de Souza Mark123,Tovanabutra Sodsai23,Schuetz Alexandra345,Robb Merlin L34,Douek Daniel C9,Phanuphak Nittaya1,Haase Ashley10,Ananworanich Jintanat34,Schacker Timothy W8ORCID

Affiliation:

1. Institute of HIV Research and Innovation , Bangkok , Thailand

2. King Chulalongkorn Memorial Hospital, Thai Red Cross Society , Bangkok , Thailand

3. US Military HIV Research Program, Walter Reed Army Institute of Research , Silver Spring, Maryland , USA

4. Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda, Maryland , USA

5. Armed Forces Research Institute of Medical Sciences , Bangkok , Thailand

6. Bamrasnaradura Infectious Disease Institute , Nonthaburi , Thailand

7. Division of Biostatistics, University of Minnesota , Minneapolis, Minnesota , USA

8. Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA

9. Vaccine Research Center, National Institutes of Health , Bethesda, Maryland , USA

10. Department of Microbiology and Immunology, University of Minnesota , Minneapolis, Minnesota , USA

Abstract

Abstract Starting antiretroviral therapy (ART) in Fiebig 1 acute HIV infection limits the size of viral reservoirs in lymphoid tissues, but does not impact time to virus rebound during a treatment interruption. To better understand why the reduced reservoir size did not increase the time to rebound we measured the frequency and location of HIV RNA+ cells in lymph nodes from participants in the RV254 acute infection cohort. HIV RNA+ cells were detected more frequently and in greater numbers when ART was initiated in Fiebig 1 compared to later Fiebig stages and were localized to the T-cell zone compared to the B-cell follicle with treatment in later Fiebig stages. Variability of virus production in people treated during acute infection suggests that the balance between virus-producing cells and the immune response to clear infected cells rapidly evolves during the earliest stages of infection. Clinical Trials Registration: NCT02919306.

Funder

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Henry M. Jackson Foundation

US DoD

Thai Government Pharmaceutical Organization

Gilead Foundation

Merck

ViiV Healthcare

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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