An SIV macaque model of SIV and HAND: the need for adjunctive therapies in HIV that target activated monocytes and macrophages.

Non-human primate models of AIDS and neuroAIDS are critical to study HIV infection of the CNS, neuropathology, and immune activation and macrophage accumulation that occurs in HAND. SIV, similar to HIV, infects CD4 T lymphocytes and monocytes/macrophages. Virus enters the CNS early, and macrophage activation correlates with CNS disease, as well as inflammation outside of the CNS. Antiretroviral in HIV+ humans and SIV+ Rhesus macaques results in non-detectable plasma virus, decreased or non-detectable viral RNA or protein in the CNS. But, viral DNA rebounds following therapy interruption, demonstrating the presence of replication competent virus in the CNS within myeloid cells. In this brief review, we discuss our findings using a Rhesus macaque model of SIV-associated CNS infection and pathology, focusing on monocyte/macrophage activation and the link between CNS and cardiac disease. We conclude with recent studies using adjunctive therapy targeting monocytes/macrophages with ART to prevent or diminish CNS pathology that may be associated with HAND.