Inflammation & Neurodegeneration in HIV-Associated Neurocognitive Disorders (HAND)

Welcome to the Brown Laboratory Research Group. We study how HIV infection and persistence in tissue macrophages contributes to the development of HIV-associated neurocognitive disorder (HAND), a co-morbidity that afflicts 50% or more of infected individuals.

There are approximately 40 million people in the world living with HIV. The availability of life-saving treatments has greatly expanded across the world allowing those infected to be productive and live to advanced ages. However, several factors including the persistence of anatomical and cellular sites where HIV reproduction continues, contribute to the development of a higher incidence of co-morbidities such as cognitive impairment and cardiovascular disease.

HIV infection stimulates both arms of the immune system–the Innate, which is the first rapid response mediated by cells including macrophages, dendritic cells and NK cells, and the Adaptive arm responsible for the production of antibodies and T-cell mediated immunity.

These responses induce inflammatory processes which are necessary to control spread of the virus. We know that immune surveillance of the brain is critical in recovery from neurological infections and injury, and likely plays a role in normal homeostasis at this site.

However, when the inflammatory response is not down-regulated back to normal levels, the result is chronic activation, which we and others think can lead to neuronal damage and neurodegeneration.

Our long-term goal is to identify the critical genes and pathways involved, and to understand how the immune response to HIV infection in brain leads to HAND. These aims are important because with the knowledge gained, we hope to develop adjunctive therapies which can protect against neuronal damage.