Human Immunodeficiency Virus type I (HIV-1) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). The virus has a multi-step life cycle that revolves around the transcriptional control of the virus as regulated by interaction between the viral Tat protein and an RNA element known as the transactivation response (TAR) element. HIV invades the CNS relatively early during infection and sets the stage for long term inflammatory events. Relatively poor penetration of the CNS by highly active anti-retroviral therapy (HAART) makes it a haven for the virus and permits ongoing inflammation that leads to moderate to potentially severe HIV-associated dementia. Drug abusers are one of the fastest growing populations of HIV infected individuals. There is considerable evidence in the literature that HIV positive drug abusers are at greater risk for HAND and generally have a heightened pathology than non-drug abusers. The objective of this project is to determine the role of miRNA alteration by Tat in perturbing signaling and inflammation in the CNS.