HIV-infected people, over 39 million worldwide, are living longer and have fewer opportunistic infections as a result of successful antiretroviral therapies (ART). Despite this success, neurologic complications of HIV infection have not declined. HIV enters the central nervous system (CNS) early after infection and despite successful therapy, persists within the CNS. More than 50% of HIV-positive people exhibit some form of HIV-associated neurocognitive impairment (HAND) as a result of HIV within the brain and the ensuing low-level inflammation and neuronal damage.
NeuroAIDS is a major public health issue for which there are currently no biomarkers or therapies. The laboratory of Joan W. Berman, PhD,examines mechanisms of HIV neuropathogenesis and potential therapies to reduce viral seeding and CNS inflammation.
The Berman laboratory studies human monocyte and T cell transmigration across the human blood brain barrier (BBB), which monocyte subset preferentially crosses the BBB, and the junctional proteins and chemotactic factors that mediate this process. Dr. Berman and her team examine tissues, cells, and fluids from HIV-positive individuals for biomarkers, junctional proteins, inflammatory factors, functional properties, and predictors of HAND. The investigators use sophisticated molecular techniques to detect HIV RNA/DNA in PBMC and tissues obtained from these individuals, and correlate the findings with neuroimaging studies, neurocognitive testing, and clinical data from them. The investigators use single-cell RNA sequencing analyses to characterize the cells that are HIV positive.
The goal: to identify biomarkers for HAND and therapeutic targets to limit/eliminate CNS infection, HIV reservoirs within the brain, and subsequent damage.
In addition, the Berman laboratory is characterizing the impact of substance abuse, specifically opioids and methamphetamine, on neuroAIDS, BBB permeability, and macrophages/microglia, as well as the role of autophagy in HAND and influence of substance abuse on autophagy. Studies are also being done to understand the mechanisms by which buprenorphine, a therapy for heroin addiction, mitigates neuroinflammation, CNS damage, and cognitive deficits in the context of HIV infection.