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; Dan H. Barouch

doi:10.1038/s41467-018-07881-9

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, Dan H. Barouch

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

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.

Original language	English
Article number	5429
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-07881-9
State	Published - 1 Dec 2018
Externally published	Yes

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Whitney, J. B., Lim, S. Y., Osuna, C. E., Kublin, J. L., Chen, E., Yoon, G., Liu, P. T., Abbink, P., Borducci, E. N., Hill, A., Lewis, M. G., Geleziunas, R., Robb, M. L., Michael, N. L., & Barouch, D. H. (2018). Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy. Nature Communications, 9(1), Article 5429. https://doi.org/10.1038/s41467-018-07881-9

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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.",

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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.

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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.

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

Abstract

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