Abstract

The precise time when the viral reservoir is seeded during acute HIV-1 infection remains unclear. We previously demonstrated that the viral reservoir was seeded by day 3 following SIVmac251 infection in rhesus monkeys. Here we report the impact of initiating ART on day 0 (6 h), 1, 2, or 3 following intrarectal SIVmac251 infection in 20 rhesus monkeys (N = 5/group). After 6 months of daily suppressive ART, antiretroviral drugs were discontinued, and viral rebound was monitored. 0% (0 of 5), 20% (1 of 5), 60% (3 of 5), and 100% (5 of 5) of animals that initiated ART on days 0 (6 h), 1, 2, or 3, respectively, showed viral rebound following ART discontinuation and correlated with integrated viral DNA in lymph node CD4+ T cells. These data demonstrate that the viral reservoir is seeded within the first few days of infection and that early ART initiation limits the viral reservoir.

Details

Title
Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy
Author
Whitney, James B 1 ; So-Yon Lim 2   VIAFID ORCID Logo  ; Osuna, Christa E 2   VIAFID ORCID Logo  ; Kublin, Jessica L 2 ; Chen, Elsa 2 ; Yoon, Gyeol 2 ; Po-Ting, Liu 2   VIAFID ORCID Logo  ; Abbink, Peter 2   VIAFID ORCID Logo  ; Borducci, Erica N 2 ; Hill, Alison 3   VIAFID ORCID Logo  ; Lewis, Mark G 4 ; Geleziunas, Romas 5 ; Robb, Merlin L 6 ; Michael, Nelson L 7 ; Barouch, Dan H 1 

1  Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA 
2  Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 
3  Program for Evolutionary Dynamics, Harvard University, Cambridge, MA, USA 
4  Bioqual, Rockville, MD, USA 
5  Gilead Sciences, Foster City, CA, USA 
6  U.S. Military HIV Research Program, Henry Jackson Foundation, Bethesda, MD, USA 
7  Walter Reed Army Institute of Research, Silver Spring, MD, USA 
Pages
1-8
Publication year
2018
Publication date
Dec 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-07881-9
ProQuest document ID
2159700889
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.