Impact of Antiretroviral Therapy Duration on HIV-1 Infection of T Cells within Anatomic Sites

Author:

Lee Eunok1,von Stockenstrom Susanne2,Morcilla Vincent1,Odevall Lina2,Hiener Bonnie1,Shao Wei3,Hartogensis Wendy4,Bacchetti Peter5,Milush Jeffrey4,Liegler Teri4,Sinclair Elizabeth4,Hatano Hiroyu4,Hoh Rebecca4,Somsouk Ma4,Hunt Peter4,Boritz Eli6,Douek Daniel6,Fromentin Remi7,Chomont Nicolas7,Deeks Steven G.4,Hecht Frederick M.4,Palmer Sarah1

Affiliation:

1. The Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia

2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

3. Advanced Biomedical Computing Center, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

4. Department of Medicine, University of California San Francisco, San Francisco, California, USA

5. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA

6. Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

7. Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Canada

Abstract

HIV-1 persists as an integrated genome in CD4 + memory T cells during effective therapy, and cessation of current treatments results in resumption of viral replication. To date, the impact of antiretroviral therapy duration on HIV-infected CD4 + T cells and the mechanisms of viral persistence in different anatomic sites is not clearly elucidated. In the current study, we found that treatment duration was associated with a reduction in HIV-infected T cells. Our genetic analyses revealed that CD4 + effector memory T (T EM ) cells derived from the lymph node appeared to contain provirus that was genetically identical to plasma-derived virions. Moreover, we found that cellular proliferation counterbalanced the decay of HIV-infected cells throughout therapy. The contribution of cellular proliferation to viral persistence is particularly significant in T EM cells. Our study emphasizes the importance of HIV-1 intervention and provides new insights into the location of memory T cells infected with HIV-1 DNA, which is capable of contributing to viremia.

Funder

amfAR, The Foundation for AIDS Research

Department of Health | National Health and Medical Research Council

Delaney AIDS Research Enterprise

Gladstone Institutes

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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