The viral reservoir represents a critical challenge for human immunodeficiency virus type 1 eradication strategies. In this study, monkeys were started on suppressive anti-retroviral therapy on days 3, 7, 10 and 14 after intra rectal SIVMac251 infection. Treatment with ARV on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced level of proviral DNA in lymph nodes and gastro-intestinal mucosa compared with treatment at later time points. In addition, treatment from day 3 abrogated induction of SIV-specific humoral and cellular immune responses. After discontinuation of ART following 24 weeks of fully suppressive therapy, virus rebounded in all animals, although the monkeys that were treated on day 3 exhibited a delayed viral rebound compared with those treated on days 7, 10 and 14. The time to viral rebound correlated with total viremia during acute infection and with proviral DNA at the time of ART discontinuation.
These data demonstrate that the viral reservoir is seeded rapidly after intra-rectal SIV infection of rhesus monkeys, during the eclipse phase, and before any detectable viraemia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies.