HIV and AIDS drug regimens have vastly improved since the disease was first identified in the early 1980s. They have saved millions of lives, but they still have drawbacks. Up to half of all people living with HIV who are on antiretroviral therapies, or ART, have some sort of cognitive impairment, such as memory loss or reduced executive function.
Researchers from Penn and the Children’s Hospital of Philadelphia (CHOP) have found new evidence implicating antiretroviral drugs in these neurocognitive conditions. Focusing on oligodendrocytes, crucial brain cells that manufacture myelin—the fatty material that insulates neurons and gives white matter its characteristic color—the scientists found that the drugs interfered with the cells’ function.
Two Penn faculty brought their complementary expertise to the table to pursue the research. Kelly Jordan-Sciutto, professor and chair of the Department of Pathology in the School of Dental Medicine, is a specialist in HIV-associated neurocognitive dysfunctions. She teamed up with Judith B. Grinspan, a research scientist at CHOP, professor of neurology at the Perelman School of Medicine, and a specialist in oligodendrocytes, to see how ART could affect these cells.
In work published in the Journal of Neuropathology and Experimental Neurology, the researchers investigated the effects of commonly used antiretroviral drugs on oligodendrocytes grown in the lab as well as on adult mice. In the cells in culture, two of the three drugs they tested reduced the cells’ ability to mature and properly make myelin. The mice treated with one of the HIV drugs also had significantly reduced levels of certain components of mature myelin.
The researchers also examined brain tissue from autopsies of HIV patients and found that those who had a diagnosis of an HIV-associated neurocognitive disorder and were also on ART had significantly less of the most critical protein component of myelin protein compared to either HIV-positive individuals who didn’t receive ART or people who were HIV-negative.
The findings shed light on the need for improved drugs that can protect people with HIV/AIDS while also reducing cognitive side effects. The researchers say the need is particularly great for children on ART, because myelin formation occurs predominantly during childhood.
“Pharmaceutical companies have done an amazing job developing drugs to make HIV patients live longer, but we’re not done,” says Jordan-Sciutto. “The message we want to get out there is that we want to make these patients’ lives better while they are on ART.”