Mouse Study: Memory Problems Observed In About Half With HIV

A new study on HIV-positive mice proves the virus causes cognitive difficulties, which can be prevented (but not reversed) by antiretroviral treatment. About half of people living with HIV now suffer from memory dysfunction, but according to research, extremely early intervention with ARTs could prevent such neurological impacts.

HIV-associated dementia, delirium, and memory loss are a consequence of HIV’s effect on the central nervous system. HIV can replicate and develop reservoirs in the brain. One of the problems of controlling HIV in the brain is finding ways to cross the blood-brain barrier — getting medication into your bloodstream will not get it into the brain due to this barrier.

The study, published in the journal PLOS Pathogens, was led by David J. Volsky and Mary Jane Potash, both from Icahn School of Medicine at Mount Sinai in New York. It’s the first time scientists were able to reproduce in mice the viral reservoirs and cognitive declines seen in people living with HIV. Investigators traced cognitive problems to active HIV in large white blood cells, which could be the reason it begins in the first place.

Mount Sinai researchers developed EcoHIV, a genetically engineered rodent version of HIV that reproduces many aspects of human contraction, so that scientists could study HIV in an animal model that closely replicates what people experience.

The mice in the study demonstrated an ability to learn (they were trained to recognize and then remember visual symbols). Within a month of becoming HIV-positive, the mice failed tests around learning and memory, and those memory problems were not reversed when the mice began antiretroviral treatment.

Researchers found that cognitive declines appeared to be preventable with the antiretroviral drug prophylaxis.

“These findings indicate that EcoHIV infection causes impairment in the cognitive abilities tested, namely, visuospatial and working memory, and contextual fear memory,” the PLOS Pathogens article noted. “Because ART prophylaxis prevented cognitive impairments in EcoHIV-infected mice, our results also link EcoHIV replication in mice to development of cognitive disease.”

The study demonstrates that HIV causes the learning and memory dysfunction that “is now observed in about half of HIV [positive] people, that worsens with age, and is currently incurable,” noted Mount Sinai Health System in a statement to the press. This is important because some earlier research suggested these cognitive issues were side effects of certain antiretroviral medications.

The research also suggests that large white blood cells (known as macrophages) may play a key role in impairing learning and memory among people with HIV. These cells are part of the body’s immune system that can destroy potential pathogens.

The role of T cells in HIV infection is well known, but in this study, the scientists had mice engineered not to have T cells — yet, when they were exposed to EcoHIV, the mice still became HIV-positive and experienced similar cognitive problems, suggesting that infected macrophages were responsible for the impairment.

According to Science Daily, “These findings add to growing evidence that macrophages harboring active HIV may transport HIV to the brain, leading to cognitive problems in [poz] people.”

Noting that “cognitive impairment is a common problem in a wide variety of human conditions, including diabetes, aging, and Alzheimer’s disease,” Dr. Volsky stated, “studies in the EcoHIV model of cognitive impairment may have broad implications for better understanding and treatment of these conditions in other disease states.”

The findings could be used to develop and test new drugs against the virus, such as those zeroing in on HIV reservoirs; and those directed specifically at preventing or  restoring healthy brain function damaged by HIV, while patients simultaneously continue on antiretroviral therapy.