@article{1f5e1e6be4284cf8af3881c178d6b507,
title = "Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound",
abstract = "Prophylactic vaccination of rhesus macaques with rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens (RhCMV/SIV) elicits immune responses that stringently control highly pathogenic SIV infection, with subsequent apparent clearance of the infection, in ~50% of vaccinees. In contrast, here, we show that therapeutic RhCMV/SIV vaccination of rhesus macaques previously infected with SIV and given continuous combination antiretroviral therapy (cART) beginning 4–9 d post-SIV infection does not mediate measurable SIV reservoir clearance during over 600 d of follow-up on cART relative to RhCMV/control vaccination. However, none of the six animals started on cART on day four or five, across both RhCMV/SIV- and RhCMV/control-vaccinated groups, those rhesus macaques with SIV reservoirs most closely resembling those of prophylactically RhCMV/SIV-vaccinated and protected animals early in their course, showed post-cART viral rebound with up to nine months of follow-up. Moreover, at necropsy, these rhesus macaques showed little to no evidence of replication-competent SIV. These results suggest that the early SIV reservoir is limited in durability and that effective blockade of viral replication and spread in this critical time window by either pharmacologic or immunologic suppression may result in reduction, and potentially loss, of rebound-competent virus over a period of ~two years.",
author = "Okoye, {Afam A.} and Hansen, {Scott G.} and Mukta Vaidya and Yoshinori Fukazawa and Haesun Park and Duell, {Derick M.} and Richard Lum and Hughes, {Colette M.} and Ventura, {Abigail B.} and Emily Ainslie and Ford, {Julia C.} and David Morrow and Gilbride, {Roxanne M.} and Legasse, {Alfred W.} and Joseph Hesselgesser and Romas Geleziunas and Yuan Li and Kelli Oswald and Rebecca Shoemaker and Randy Fast and Bosche, {William J.} and Borate, {Bhavesh R.} and Edlefsen, {Paul T.} and Axthelm, {Michael K.} and Picker, {Louis J.} and Lifson, {Jeffrey D.}",
note = "Funding Information: This work was supported by the US National Institutes of Health (grants U19AI096109, U19AI095985, UM1AI126611, UM1AI124377, R37AI054292, and P51OD011092, L.J.P.), by the Bill and Melinda Gates Foundation (grant OPP1094567, L.J.P.), and supported in part with federal funds from the National Cancer Institute, National Institutes of Health (Contract No. HHSN261200800001E, J.D.L.). 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. The authors thank B. Keele (Leidos Biomedical Research, Inc.) for providing SIVmac239X and Janssen Pharmaceuticals for providing Darunavir. The CD8+ lymphocyte-depleting monoclonal antibody, M-T807R1, was provided by the National Institutes of Health{\textquoteright}s Nonhuman Primate Reagent Resource Program. We thank A. Sylwester, S. Hagen, T. Swanson, M. Fischer, S. Planer, C. Kahl, D. Siess, M. Reyes, J. Clock, A. Konfe, C. Abana, C. Pexton, E. McDonald, K. Jeffries, M. Grey, C. Xu, W. Brantley, A. Maxwell, M. Lidell, D. Malouli, M. Marenco, A. Townsend, and L. Boshears for technical or administrative assistance. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = sep,
day = "1",
doi = "10.1038/s41591-018-0130-7",
language = "English (US)",
volume = "24",
pages = "1430--1440",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "9",
}