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

Nat Commun. 2018 Dec 21;9(1):5429. doi: 10.1038/s41467-018-07881-9.

Authors

James B Whitney^{1

2}, So-Yon Lim³, Christa E Osuna³, Jessica L Kublin³, Elsa Chen³, Gyeol Yoon³, Po-Ting Liu³, Peter Abbink³, Erica N Borducci³, Alison Hill⁴, Mark G Lewis⁵, Romas Geleziunas⁶, Merlin L Robb⁷, Nelson L Michael⁸, Dan H Barouch^{9

10}

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. jwhitne2@bidmc.harvard.edu.
² Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA. jwhitne2@bidmc.harvard.edu.
³ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
⁴ Program for Evolutionary Dynamics, Harvard University, Cambridge, MA, 02138, USA.
⁵ Bioqual, Rockville, MD, 20852, USA.
⁶ Gilead Sciences, Foster City, CA, 94404, USA.
⁷ U.S. Military HIV Research Program, Henry Jackson Foundation, 6720 Rockledge Drive, Bethesda, MD, 20817, USA.
⁸ Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
⁹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. dbarouch@bidmc.harvard.edu.
¹⁰ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA. dbarouch@bidmc.harvard.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Retroviral Agents / administration & dosage*
CD4-Positive T-Lymphocytes / immunology
Drug Therapy, Combination
Macaca mulatta
Male
Models, Biological
Simian Acquired Immunodeficiency Syndrome / immunology
Simian Acquired Immunodeficiency Syndrome / prevention & control
Simian Acquired Immunodeficiency Syndrome / virology*
Simian Immunodeficiency Virus / immunology

Substances

Anti-Retroviral Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding