Novel Imaging Approaches for Detection of Persistent HIV in the CNS, HIV-Associated Inflammation, and Molecular Pathology

Presenter:

Dianne Rausch, Ph.D.    
Division of AIDS Research

Purpose:

The goal of this initiative is to encourage the use of current and novel imaging technologies to detect persistent, latent, and/or reactivated HIV, HIV viral products and associated pathology/inflammation in the central nervous system (CNS) in virally suppressed individuals on ART.

Rationale:

Mild to moderate CNS dysfunction continues to persist despite viral suppression in HIV-infected individuals on ART. The CNS is also considered a potential viral reservoir and one of the key barriers to HIV cure efforts. Given the change in the clinical trajectories and pathology associated with HIV-induced CNS dysfunction in the post-ART era, there is a need to better understand the role of chronic inflammation as well as the macro and molecular pathology of mild to moderate forms of CNS dysfunction in virally suppressed individuals on ART.

Noninvasive detection strategies are needed to overcome the unique challenges of detecting HIV in the brain, where tissue sampling may be difficult and invasive. Novel imaging approaches combined with biomarkers offer a potential means to detect virus and associated pathology/inflammation that could be targeted by therapeutic strategies. Discovery of novel imaging signatures to detect persistent/latent viral infection, viral proteins such as Tat, and the causes of neuronal dysfunction in virally suppressed individuals on ART could lead to the development of more sensitive diagnostic tests. Such discoveries will aid in developing interventions that target HIV-associated CNS disease as well as CNS viral reservoirs with greater specificity.

This initiative encourages research in the following areas:

• Refinement of imaging technologies to detect persistent virus/viral products as well as reactivated virus in the CNS compartment;
• Development of novel imaging technologies to detect HIV-induced inflammation in the CNS, as well as associated synaptic/ molecular pathology in virally suppressed individuals on ART;
• Refinement and utilization of imaging technologies such as positron emission tomography (PET) in conjunction with antibody based immune recognition approaches to analyze the distribution of CNS virus reservoirs, provide improved delineation of spatial kinetics of viral spread, detect markers of chronic HIV-induced CNS inflammation and the associated pathology in virally suppressed individuals on ART;
• Utilization of novel in vitro/in vivo models to investigate the role of HIV-associated inflammation caused by persistent/latent HIV infection of the CNS on both functional and structural neuronal connectivity specifically in the context of ART.