Abstract: Migration of HIV-1 infected monocytes across the endothelial barrier plays an essential role in establishing and maintenance of viral reservoir in the brain and leads to neuroinflammation, neuronal damage, and subsequent HIV-induced central nervous system (CNS) dysfunction. These processes continue despite antiretroviral therapy (ART) due to limited pharmacological permeability of the blood-brain barrier, the presence of residual viral replication, and the reactivation of latent viruses. Compositions comprising Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonucleases targeted to activated leukocytes cell adhesion molecule (ALCAM/CD166), chemotactic recruitment (CCR2/5), adhesion to the endothelium (ALCAM) and junctional diapedesis (JAM-A) achieves maximum repression of leukocyte transmigration and block of the spread of the virus to different tissues and organs.

Abstract: The invention is generally related to assays and methods for determining the risk of an HIV+ individual for developing a macrophage-mediated disease using measurement of soluble CD163 levels in a biological sample. The invention also provides assays and methods for monitoring efficacy of a treatment or a drug for a macrophage-mediated disease, and assays and methods for screening for agents to treat a macrophage-mediated disease in an HIV+ individual by monitoring soluble CD163 levels.