Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy

James B. Whitney (), So-Yon Lim, Christa E. Osuna, Jessica L. Kublin, Elsa Chen, Gyeol Yoon, Po-Ting Liu, Peter Abbink, Erica N. Borducci, Alison Hill, Mark G. Lewis, Romas Geleziunas, Merlin L. Robb, Nelson L. Michael and Dan H. Barouch ()
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James B. Whitney: Harvard Medical School
So-Yon Lim: Harvard Medical School
Christa E. Osuna: Harvard Medical School
Jessica L. Kublin: Harvard Medical School
Elsa Chen: Harvard Medical School
Gyeol Yoon: Harvard Medical School
Po-Ting Liu: Harvard Medical School
Peter Abbink: Harvard Medical School
Erica N. Borducci: Harvard Medical School
Alison Hill: Harvard University
Mark G. Lewis: Bioqual
Romas Geleziunas: Gilead Sciences
Merlin L. Robb: Henry Jackson Foundation
Nelson L. Michael: Walter Reed Army Institute of Research
Dan H. Barouch: Harvard Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07881-9

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