TY - JOUR
T1 - Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy
AU - Whitney, James B.
AU - Lim, So Yon
AU - Osuna, Christa E.
AU - Kublin, Jessica L.
AU - Chen, Elsa
AU - Yoon, Gyeol
AU - Liu, Po Ting
AU - Abbink, Peter
AU - Borducci, Erica N.
AU - Hill, Alison
AU - Lewis, Mark G.
AU - Geleziunas, Romas
AU - Robb, Merlin L.
AU - Michael, Nelson L.
AU - Barouch, Dan H.
N1 - Funding Information:
We thank J. Hesselgesser, J. Harrison, C. Gittens, J. Yalley-Ogunro, H. Anderson, and W. Wagner for expert animal husbandry and care. We acknowledge support from the US Army Medical Research and Materiel Command and the US Military HIV Research Program, Walter Reed Army Institute of Research through its cooperative agreement with the Henry M. Jackson Foundation for the Advancement of Military Medicine (W81XWH-11-2-0174); the NIH (AI091514, AI096040, AI122942, AI124377, AI126603, AI127089, AI128751, AI131365); and the Ragon Institute of MGH, MIT, and Harvard.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85058918145&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-07881-9
DO - 10.1038/s41467-018-07881-9
M3 - Article
C2 - 30575753
AN - SCOPUS:85058918145
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5429
ER -