Understanding the Mechanisms of Neuropsychiatric Side Effects and Neurological Toxicities of HIV Anti-Retroviral Therapy (ART)

Presenter:

Dianne Rausch, Ph.D.
Division of AIDS Research

Goal:

The goal of this initiative is to encourage innovative research to identify risk-factors and understand mechanisms underlying neuropsychiatric side effects and neurological toxicities associated with HIV treatment, and to identify modifiable targets or individuals at high risk for timely interventions.

Rationale:

Recent evidence indicates optimal health outcomes and prevention of further transmission can occur when ART is initiated early after infection and adherence to treatment is maintained. However, neuropsychiatric side effects including depression and anxiety disorders, sleep disorders, suicidal ideation, developmental disorders and neurological toxicities such as neural tube defects have been reported in a subset of individuals taking ART. The impact of side effects and toxicities associated with ART are often realized in the post-market analysis when additional clinical research and patient complaints contribute to a broadened perspective on a drug. These side effects and toxicities may lead individuals to refrain from or discontinue the use of vital HIV therapy.

This initiative will encourage research to identify potential mechanisms and risk factors underlying these neuropsychiatric and neurological symptoms and toxicities which could be targets for therapeutic interventions or personalized medicine.

Research topics of interest include studies designed to:

• Determine individual predictors of neuropsychiatric adverse events, or alternative factors driving neuropsychiatric side effects and neurotoxicities with ART exposure. These may include polypharmacy, psychotropic drugs and drug-drug interactions as well as mental health history and genetic factors;/li>
• Identify the mechanisms involved in ART-induced neuropsychiatric effects;
• Investigate the potential for cumulative neurotoxic effects with ART;
• Develop and test innovative ways to measure ART-induced neuropsychiatric adverse events;
• Design preventative and/or therapeutic strategies to avoid or overcome the neuropsychiatric side effects following ART exposure.