@article{1c7f687ba8cd44b6aed08fd45ee1e81b,
title = "CD8+ Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy",
abstract = "Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8–32 week) ART, depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8+ T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.",
author = "Cartwright, {Emily K.} and Lori Spicer and Smith, {S. Abigail} and David Lee and Randy Fast and Sara Paganini and Lawson, {Benton O.} and Melon Nega and Kirk Easley and Schmitz, {Joern E.} and Bosinger, {Steven E.} and Mirko Paiardini and Ann Chahroudi and Vanderford, {Thomas H.} and Estes, {Jacob D.} and Lifson, {Jeffrey D.} and Derdeyn, {Cynthia A.} and Guido Silvestri",
note = "Funding Information: We thank J. Levy, D.G. Carnathan, M. Mavigner, C.S. McGary, and G. Mylvaganam for helpful discussions; B. Cervasi, K.P. Gill, and J.P. Mackel for technical support; S. Ehnert for study organization and scheduling; Yerkes National Primate Research Center (YNPRC) veterinary staff, especially S. Jean, for caring for the animals and daily ART administration; Merck (I.MTA.14.232) Gilead Sciences (I.MTA.14.230) for generously providing Raltegravir, PMPA, and FTC; and Janssen R&D Ireland (I.MTA.14.231) for providing Darunavir. We thank the Emory CFAR Virology Core for viral loads and the Emory CFAR Immunology Core for use of the MiSeq platform. This work was funded in part by NIH grants R01-AI90797 (to G.S.), RR000165/OD011132 (to the YNPRC), and P30-AI-50409, R01 AI-58706, and U19 AI-109633 (to C.D.), the Emory CFAR, and federal funds from the NIH National Cancer Institute (contract HHSN261200800001E with J.L.). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = sep,
day = "20",
doi = "10.1016/j.immuni.2016.08.018",
language = "English (US)",
volume = "45",
pages = "656--668",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",
}