Proposed timeline for HIV-1 Vpr mediated pathology and resistance to therapy. Early in infection, Vpr allows for productive viral infection of macrophages. These cells contribute to virus production and drug resistant reservoirs seen throughout the infection. During clinical latency, Vpr contributes to the depletion of CD4+ and CD8+ T-cells, as well as interferes with antigen presentation. Such properties may contribute to HIV-1 escape from immune surveillance, and effective humoral control of HIV infection. While it is yet unclear if neurocognitive dysfunction and HIV-D are related pathologies, Vpr mediated immune dysregulation and neurotoxicity may contribute to early neurological impairment in HIV-1 patients. Late in HIV-1 pathogenesis, increased expression of viral proteins including Vpr, contributes to the development of associated pathologies, such as HIV-D and HIVAN.