Step 1: After interruption of antiretroviral therapy, viral recrudescence from HIV-infected CD4+ T cells occurs in the tissues. Step 2: Successful viral replication leads to the recruitment of innate immune cells, including pDCs, which are one of the first to respond to initial HIV infection. pDC sensing of virus at the site of recrudescence results in their activation and rapid cytokine production. Step 3: Production of CCL4 by activated pDCs can recruit more CD4+ T cells to the site of viral replication, resulting in further viral propagation and, eventually, measurable virus in the blood. Step 4: Our data demonstrate an increased frequency of pDCs in the blood prior to detection of plasma viremia after ATI. These pDCs expressed the activation markers CD69, PD-L1, and CD40 as well as increased levels of CXCR4 and CD29, suggesting that they were trafficking to sites of inflammation. Step 5: pDCs in the blood showed a transient decline in the ability to produce IFNα after stimulation in vitro, indicating that they enter a state of refraction after in vivo activation.