Lentivirus infections are characterized by a dramatic loss of mucosal CD4⁺ T cells, breakdown of the gut mucosa, and subsequent chronic immune activation. Residual immune activation persists even in patients controlling virus replication and remains a significant source of ongoing disease morbidities, but the causes are unclear. Plasmacytoid dendritic cells (pDCs), primary producers of interferon (IFN)-α, have been previously shown to be depleted from peripheral blood of HIV patients and simian immunodeficiency virus (SIV)-infected macaques, and most recently have been shown to accumulate in the gut mucosa. Although previous work has shown that pDC frequencies can be reduced in the circulation of HIV-1 Elite Controllers, it is unknown if gut-homing also occurs. In this new study we found that during progressive HIV-1 infection pDCs were depleted in peripheral blood compared to seronegative controls, and, correlating with plasma viremia, the remaining pDCs upregulated the gut-homing marker, α₄β₇. Even in HIV-1 Elite Controllers pDCs were significantly reduced in blood and α₄β₇ expression was still significantly upregulated compared to seronegative controls. Interestingly, pDC trafficking to the gut was associated with increased Ki67 and HLA-DR on circulating CD4⁺ and CD8⁺ T cells. Overall, these data suggest that gut trafficking of pDCs is independent of virus replication and could be mediated by alternative mechanisms, which in turn could contribute to residual immune activation in HIV-1 Elite Controllers.