Nevertheless, following discontinuation of ART after 24 weeks of fully suppressive therapy, virus rebounded in all animals, although animals treated on day 3 exhibited a delayed viral rebound as compared with animals treated on days 7, 10 and 14. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Treatment on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later timepoints. We initiated suppressive ART in groups of monkeys on days 3, 7, 10, and 14 following intrarectal SIVmac251 infection. Here we show that the viral reservoir is seeded very early following mucosal SIV infection of rhesus monkeys and prior to systemic viremia. However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). The viral reservoir represents a critical challenge facing HIV-1 eradication strategies 1– 5.
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