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

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19 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 (US)
Article number	5429
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-07881-9
State	Published - Dec 1 2018
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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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title = "Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy",

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.",

author = "Whitney, {James B.} and Lim, {So Yon} and Osuna, {Christa E.} and Kublin, {Jessica L.} and Elsa Chen and Gyeol Yoon and Liu, {Po Ting} and Peter Abbink and Borducci, {Erica N.} and Alison Hill and Lewis, {Mark G.} and Romas Geleziunas and Robb, {Merlin L.} and Michael, {Nelson L.} and Barouch, {Dan H.}",

note = "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: {\textcopyright} 2018, The Author(s).",

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doi = "10.1038/s41467-018-07881-9",

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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.

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

Abstract

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