Underlying Mechanisms of HIV-Associated Neurocognitive Disorders

HIV patients lack crucial peroxisomal proteins in the brain.

Individuals with HIV often suffer from neurocognitive disorders. In a new study published in PLOS Pathogens, investigators found the underlying mechanisms why HIV-associated neurocognitive disorders (HAND) are common among this patient population.

An estimated 1 of 4 patients with HIV have HAND, and nearly 10 million individuals worldwide are thought to be living with neurocognitive disorders that emerge from the infection.

“Even though we have wonderful antiretroviral drugs for controlling HIV in the blood—–which we can do very effectively––we still have brain disease,” said investigator Chris Power. “We think it’s because the antiviral drugs don’t get into the brain and don’t target the infected cells very well. So the virus is lingering in the brain, causing damage to peroxisomes, which in turn causes brain disease.

“It is very disabling. People are unable to work. They end up in assisted living. It is a huge problem because we don’t have any treatment for it.”

For the study, investigators compared the brain tissue of 10 HIV-positive individuals with no neurological symptoms with the brain tissue of 20 patients with HAND.

The results of the study showed that patients with HAND had elevated levels of microRNAs that affect the expression of proteins that are crucial for the development of peroxisomes.

“A number of critical peroxisomal proteins—–which are extraordinarily important for brain development and function––were virtually absent in the brains of HIV patients,” said investigator Tom Hobman.

Peroxisomes are a membrane-bound organelle that occurs in the cytoplasm of eukaryotic cells and play a key role in the oxidation of specific biomolecules.

Currently, the investigators are examining new ways to test for the loss of peroxisomes via easier access tissues, such as white blood cells.

“There are already very well-tolerated drugs available that regulate the activity of peroxisomes,” Hobman said. “Can these drugs be used as an adjuvant therapy along with the antiviral drugs to mitigate some of these issues? We don’t know. But the fact that some of these drugs are already Food and Drug Administration approved, it makes the road that much shorter if they were ever to be considered for this process.”

Power noted, “It is potentially a very bright spot in this story.”