Recent studies have confirmed that the human immunodeficiency virus (HIV) can hide in the brain. Microglia cells, which are part of the brain’s own specialized immune system, act as a permanent reservoir for the virus. This is the first direct evidence of the latent presence of HIV in the brain.
The normal life cycle of HIV requires it to make a copy of its genetic material and insert it into human host cells. It usually affects a certain subset of white blood cells, a key part of the immune system. The gradual loss of these cells as they succumb to the virus is why HIV causes decreased immune function and, if left untreated, acquired immune deficiency syndrome (AIDS).
Sometimes, however, HIV-infected cells go the other way, to what is known as latency. These cells become dormant or inactive and can remain in this state for years.
While current treatments can allow HIV-positive people to reach “undetectable” status, meaning that the infection is under control and they can no longer transmit the virus to others, there is nothing they can do for these dormant cells. If treatment is ever stopped, the latent infection can resume, leading to a relapse of the active disease.
The study showed that not only is HIV dormant in a small number of infected blood cells, but it also has another place to hide: inside the brain.
“We now know that microglial cells serve as a permanent reservoir of the brain,” said first author Dr. Yuyan Tan, an assistant professor at the University of North Carolina at Chapel Hill (UNC), in a statement. “This has been suspected in the past, but there has been no evidence in humans.”
The breakthrough came from a special research program called “The Last Gift.” “Samples were taken from people living with HIV who were on therapy but had encountered some deadly disease,” explained study co-author Dr. David Margolis, director of the HIV Treatment Center at the University of North Carolina. “They were willing not only to donate their bodies to science, but to participate in a research program months before they died. This extraordinary program made this important research possible.”
In addition to being able to study vital donated brain tissue samples, the researchers also conducted several experiments on macaque brain cells infected with monkey immunodeficiency virus (SIV), a close relative of HIV.
This discovery provides a new target for HIV treatment. Although there are many drugs that can inhibit HIV replication in the blood, none of them can effectively treat latent infection in the brain. According to Dr. Tan, this discovery could lead to the development of new drugs aimed at destroying the dormant cells where HIV hides.
“Our study underscores the need to develop new approaches to treating HIV infection,” Dr. Margolis said. “If we want to achieve a complete cure, we must destroy all hidden reservoirs of the virus, including those in the brain.”
The discovery could also help in understanding other untreatable diseases that may be hiding in dormant cells.
