Pathogenic Mechanisms influencing Blood Brain Barrier function in HIV and Substance Use Disorders (R01 Clinical Trial Optional)

The blood brain barrier (BBB) is a target of both the HIV virus and substances of abuse. It is a site of entry for HIV infected monocytes and macrophages that can traverse the BBB either paracellularly or transcellularly. HIV viral proteins can also attack astrocytes and tight junctions of BBB directly and compromise its integrity, resulting in the crossing of the virus, as well as abused substances, into the brain. Meanwhile, many substances of abuse cause BBB dysfunction. Because BBB integrity regulates both substances and virus levels in the brain, it is critical to establish the mechanisms by which HIV infection, in combination with substances of abuse, affect BBB function and integrity and their consequences. The purpose of this initiative is to support innovative research that elucidates the roles of HIV and addictive substances in the pathology of BBB. This FOA encourages studies to expand the current understanding of the basic molecular mechanisms underlying virus mobilization across BBB, and pathology of BBB in HIV infection and substance use disorders (SUD). In addition, studies are encouraged to develop and test novel BBB models to assess the delivery of pharmacological and immunotherapies to treat HIV infection and SUD, and to suppress HIV replication in CNS.