Africa: HIV Enters the Brain and Doesn't Leave - Paradoxically, Drugs Intended to Reduce Brain Inflammation Increase Virus Levels

HIV can damage the brain and cause memory and cognitive problems. And once HIV enters the brain, it does not leave.

HIV targets a type of immune cell called helper T cells. These immune cells move throughout the body, including the brain, constantly scanning for pieces of foreign proteins called antigens that typically indicate the presence of a pathogen. When helper T cells detect antigens, they activate other immune cells to clear the infection.

Because HIV infects and depletes helper T cells, it weakens a person's immune defenses and increases their risk of opportunistic infections, leading to AIDS.

Fortunately, there are lifesaving antiviral drugs that can control HIV and preserve helper T cells. But these antiviral drugs are unable to effectively cross into the brain and spinal cord.

My laboratory studies how helper T cells work, with the goal of developing HIV vaccines and treatments for neurodegenerative diseases. When helper T cells carry HIV into the brain, the virus hides in cells and causes persistent inflammation. This damage can accelerate brain aging.

Currently, there are no treatments to clear HIV from the brain and spinal cord. Researchers have been looking into ways to reduce the stubborn inflammation HIV causes in the central nervous system. But working with our colleagues in the Morrison Lab at UC Davis and the Raeman Lab at the University of Pittsburgh, our study found that a therapy designed to reduce inflammation in the brain and spinal cord can backfire. Instead, it increased virus levels in the brain.

T cells survey the brain and spinal cord using proteins called integrins. Embedded on the surface of cells, integrins allow immune cells to enter different areas of the body.

Researchers are studying whether blocking integrins could help combat inflammation in the brain by blocking immune cells from carrying HIV into the central nervous system. Our team tested this theory by giving rhesus macaque monkeys infected with SIV - a version of HIV that infects nonhuman primates - a multiple sclerosis drug that targets integrins.

However, when our team blocked an integrin called alpha-4 that allows T cells to migrate into the brain, we found that the amount of virus in the brain did not decrease. In fact, the viral load in some brain areas actually increased.

We took a closer look to figure out why virus levels unexpectedly increased. Blocking the alpha-4 integrin that allow helper T cells into the brain didn't decrease the level of those immune cells in the brain, we found. It actually reduced the numbers of another type of immune