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

Autor: Whitney JB; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. jwhitne2@bidmc.harvard.edu.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA. jwhitne2@bidmc.harvard.edu., Lim SY; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Osuna CE; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Kublin JL; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Chen E; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Yoon G; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Liu PT; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Abbink P; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Borducci EN; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Hill A; Program for Evolutionary Dynamics, Harvard University, Cambridge, MA, 02138, USA., Lewis MG; Bioqual, Rockville, MD, 20852, USA., Geleziunas R; Gilead Sciences, Foster City, CA, 94404, USA., Robb ML; U.S. Military HIV Research Program, Henry Jackson Foundation, 6720 Rockledge Drive, Bethesda, MD, 20817, USA., Michael NL; Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA., Barouch DH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. dbarouch@bidmc.harvard.edu.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA. dbarouch@bidmc.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Dec 21; Vol. 9 (1), pp. 5429. Date of Electronic Publication: 2018 Dec 21.
DOI: 10.1038/s41467-018-07881-9
Abstrakt: 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.
Databáze: MEDLINE
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