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

Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy
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DOI:
10.1038/s41467-018-07881-9
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发表时间:
2018-12-21
影响因子:
16.6
通讯作者:
Barouch, Dan H.
Barouch, Dan H.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Whitney, James B.;Lim, So-Yon;Barouch, Dan H.

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在急性HIV-1感染期间,病毒储存库播种的确切时间尚不清楚。我们先前证明了SIVmac 251感染恒河猴后第3天病毒库被接种。在这里,我们报告了在20只恒河猴(N = 5/组)中直肠内SIVmac 251感染后第0天(6小时)、第1天、第2天或第3天开始ART的影响。在6个月的每日抑制性ART治疗后,停用抗逆转录病毒药物,并监测病毒反弹。在第0天(6 h)、第1天、第2天或第3天开始ART的动物中,分别有0%(0/5)、20%(1/5)、60%(3/5)和100%(5/5)的动物在ART停药后显示病毒反弹,并与淋巴结CD 4 + T细胞中整合的病毒DNA相关。这些数据表明,病毒库在感染的最初几天内接种,早期ART启动限制了病毒库。
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.