Grant: Project Grant

Soon after a person is infected with HIV-1, the virus enters the brain. It stores itself in specific types of brain cells. About one in four people with HIV/AIDS develops a dementia-like brain disorder even when they get antiretroviral therapy (ART). ART does not remove all virus from the brain, even when ART eliminates virus from blood. We do not yet know what allows HIV-1 to persist in the brain even when ART removes it from a person's blood and other parts of their body. This may depend on the specific variety of HIV-1 virus, a person's sex, age and natural immunity, or how effective the ART drugs are. Not all current ART drugs work efficiently in the types of brain cells that HIV-1 infects. These drugs also may not penetrate brain tissue easily. We have a major gap in what we know about how different types of ART affect virus that persists in the brain. This gap is an obstacle to improving health care of people with HIV-1 infection, especially those with HIV-related brain disease. It is also an obstacle to fully curing HIV/AIDS. In our research, we will first investigate how virus persists in a person's brain even when ART drugs have removed virus from their blood. How does the virus affect the brain so that the virus can persist? With that information, we can develop ways to reduce virus in the brain. We have unique resources to meet these goals: 1) Archived brain samples from people with HIV/AIDS who received ART 2) Laboratory models of brain infection with HIV-1 From our studies, we expect to learn about how the virus reproduces and persists in specific types of brain cells. We will also learn about how it causes brain disease. We will better understand which ART drugs are efficient in infected brain cells. We will model how the virus stores itself in brain and examine how those stores respond to ART drugs. These new insights into the mechanisms of HIV-1 disease may lead to new therapies and new approaches to fully removing HIV-1 from a person's body.