Philadelphia, USA – Antiretroviral therapies (ART) have enabled people with HIV/AIDS to live much longer lives, essentially transforming the disease into a chronic condition. Yet concerns for these patients remain. Up to half of people with HIV on these drug regimens have some sort of cognitive impairment, such as memory loss or problems with executive functioning, despite the virus being almost undetectable in their bodies.
In a new study, researchers from Penn Dental Medicine and The Children’s Hospital of Philadelphia teamed up to investigate the underlying reasons for these impairments. They found that commonly used antiretroviral medications (protease inhibitors Ritonavir and Lopinavir) disrupted the differentiation of oligodendrocytes, crucial brain cells that manufacture myelin, the fatty material that serves to insulate neurons, helping them transmit signals in the brain fast and efficiently.
This disruption, the researchers said, may be responsible for some of the cognitive problems that HIV patients experience, and point to a need for rethinking how HIV drugs are designed and prescribed, particularly for children on ART, in whom myelin is still forming at high rates.
“Pharmaceutical companies have done an amazing job developing drugs to make HIV patients live longer, but we’re not done,” said Kelly L. Jordan-Sciutto, professor and chair of Penn Dental Medicine’s Department of Pathology, who co-led the research with Judith B. Grinspan, a research scientist at CHOP and professor of neurology at Penn’s Perelman School of Medicine. “The message we want to get out there is that we want to make these patients’ lives better while they are on ART.”
The research was published this November in the Journal of Neuropathology and Experimental Neurology.
The researchers have yet to determine a mechanism by which myelin protein levels are altered with ART, but are investigating a number of avenues. They are also evaluating how different HIV medications can affect oligodendrocyte and myelin formation, as the recommended drug cocktails frequently change.
The implications of these findings may be particularly important for paediatric patients, some of whom may have been on ART from birth. Since HIV-infected children exhibit higher rates of neurocognitive disorders such as seizures, depression and ADHD, the researchers stress that a revised look at treatments for paediatric patients may be warranted, or an additional therapy to prevent the white matter loss in both adults and children could be developed to go hand in hand with the ART.