@article{781573c12769457d985d22e5b142daf3,
title = "Antibody-mediated depletion of viral reservoirs is limited in SIV-infected macaques treated early with antiretroviral therapy",
abstract = "The effectiveness of virus-specific strategies, including administered HIV-specific mAbs, to target cells that persistently harbor latent, rebound-competent HIV genomes during combination antiretroviral therapy (cART) has been limited by inefficient induction of viral protein expression. To examine antibody-mediated viral reservoir targeting without a need for viral induction, we used an anti-CD4 mAb to deplete both infected and uninfected CD4+ T cells. Ten rhesus macaques infected with barcoded SIVmac239M received cART for 93 weeks starting 4 days after infection. During cART, 5 animals received 5 to 6 anti-CD4 antibody administrations and CD4+ T cell populations were then allowed 1 year on cART to recover. Despite profound CD4+ T cell depletion in blood and lymph nodes, time to viral rebound following cART cessation was not significantly delayed in anti-CD4-treated animals compared with controls. Viral reactivation rates, determined based on rebounding SIVmac239M clonotype proportions, also were not significantly different in CD4-depleted animals. Notably, antibody-mediated depletion was limited in rectal tissue and negligible in lymphoid follicles. These results suggest that, even if robust viral reactivation can be achieved, antibody-mediated viral reservoir depletion may be limited in key tissue sites.",
author = "Swanstrom, {Adrienne E.} and Immonen, {Taina T.} and Kelli Oswald and Cathi Pyle and Thomas, {James A.} and Bosche, {William J.} and Lorna Silipino and Michael Hull and Laura Newman and Vicky Coalter and Adam Wiles and Rodney Wiles and Jacob Kiser and Morcock, {David R.} and Rebecca Shoemaker and Randy Fast and Breed, {Matthew W.} and Joshua Kramer and Duncan Donohue and Tyler Malys and Fennessey, {Christine M.} and Trubey, {Charles M.} and Claire Deleage and Estes, {Jacob D.} and Lifson, {Jeffrey D.} and Keele, {Brandon F.} and {Del Prete}, {Gregory Q.}",
note = "Funding Information: We thank George Muthua and the animal care staff of the Laboratory Animal Sciences Program, Frederick National Laboratory, for expert animal care and support. We also thank Miles Davenport for helpful discussions. The anti-CD4 Ab administered to macaques on this study and the CD38-PE Ab used for flow cytometry were obtained from the NIH Nonhuman Primate Reagent Resource (R24 OD010976, U24 AI126683). This project has been funded in part with federal funds from the National Cancer Institute, NIH, under contract numbers HHSN261200800001E and 75N91019D00024 with additional partial support by the National Institute of Allergy and Infectious Diseases of the NIH under award number UM1AI126611. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. Publisher Copyright: {\textcopyright} 2021 American Society for Clinical Investigation. All rights reserved.",
year = "2021",
month = mar,
day = "15",
doi = "10.1172/JCI142421",
language = "English (US)",
volume = "131",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",
}