Central nervous system efficacy of HIV antiretroviral therapy
The goal of the Williams Lab is to identify the cellular and molecular mechanisms by which HIV, drugs of abuse, and the antiretroviral therapies (ART) used to treat the virus synergize to promote damage to the central nervous system (CNS).
One of the major challenges in HIV eradication is the existence of anatomic reservoirs – organs in which sustained viral replication occurs despite successful treatment with ART. The brain represents one of the most challenging HIV reservoirs, as it is infected as early as eight days after primary infection and is separated from the rest of the body by the blood-brain barrier (BBB), which prevents ART from freely entering into the brain. As a result, HIV in the brain is not quelled to the same extent as to what occurs in peripheral organs.
Currently, a major focus of the Williams Lab is to 1) identify the drug transporters that facilitate ART extravasation across the BBB, 2) characterize the penetrance of ART into distinct anatomic brain regions, and 3) determine efficacy of ART resident brain cells susceptible to HIV infection, including microglia and astrocytes, in the context of drug abuse.