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Altered Neural Pathways, Receptors and Networks in HIV-induced CNS Dysfunction

NAMHC Concept Clearance

Presenter:

Dianne Rausch, Ph.D.
Division of AIDS Research

Goal:

The goal of this initiative is to encourage research on understanding altered neuronal networks and pathways in HIV-1 induced central nervous system (CNS) dysfunction in the context of viral suppression and antiretroviral therapy (ART), by utilizing novel research models and diagnostic tools to bridge the gap between pathogenesis research and observed clinical outcomes.

Rationale:

The majority of the basic NeuroAIDS research has focused on outcomes seen in the pre-antiretroviral therapy (ART) era. Such efforts focus on neuronal damage in the context of active viral replication and look at outcomes such as encephalitis and neuronal death. With the 90-90-90 goal and new World Health Organization (WHO) guidelines, a large percentage of individuals with HIV are on treatment and getting treated early. Thus, it is critical to examine neuronal impairment caused by HIV in the context of ART. Also, the clinical presentation of neuronal dysfunction among individuals with HIV has significantly evolved. The symptoms specific to HIV-1 induced CNS pathology are seldom seen in ART suppressed individuals who exhibit mild to moderate forms of cognitive dysfunction.

Thus, there is a need to bridge the gap between disease etiology research and observed clinical outcomes. As such, it is important to consider moderating factors like the impact of ART, chronicity of infection, and aging. Newer models are needed that take advantage of advances in our understanding of neuronal networks, neural receptors and pathways. As well, there is a need to develop/adapt quantitative bio-medical diagnostic tools that can give us the true clinical picture of the nature and extent of neurocognitive impairment. Such tools would diminish reliance on neuropsychiatric batteries.

A focused funding opportunity announcement (FOA) would help foster change by encouraging researchers to decipher the causal role played by altered neuronal networks, neural receptors and pathways in the mild to moderate HIV-1 induced CNS dysfunction that is observed in clinical studies.

This initiative encourages research in the following areas:

  • Basic research on neuronal dysfunction using novel in vitro and in vivo neuro-electrophysiological techniques pursuing outcomes related to mild to moderate HIV-1 induced CNS dysfunction;
  • In vitro and in vivo models to investigate the abnormalities in neuronal receptors, neural activity and neural networks that represent current clinical outcomes specific to the context of ART;
  • Clinical studies to adapt existing diagnostic neuroimaging- and electrophysiology-based methods to measure and monitor activity of neuron ensembles and pathways;
  • Novel technologies like virtual reality, 3D organoids, magnetoencephalography (MEG), neural probes, ultrasonic neuro-modulation and photonics to decipher underlying pathophysiology of mild to moderate forms of HIV-1 induced CNS dysfunction.