HIV May Lie Dormant in Brain Cells

A new study confirms that cells regulating brain development can be a reservoir for latent immunodeficiency virus-1 (HIV).

When HIV infects human cells, it inserts a copy of its DNA into a host’s cells. Some of these infected cells can then transition into a dormant, latent state for a long time, referred to as HIV latency.

Current treatments, such as antiretroviral therapy (ART), can successfully prevent the virus from replicating further, but they cannot eradicate latent HIV. As a result, finding ways to target and clear out latent reservoirs remains a major challenge.

A new study by researchers at the UNC School of Medicine, University of California San Diego, Emory University, and the University of Pennsylvania confirms that microglial cells can serve as a stable viral reservoir for latent HIV. With a decade-long lifespan, these cells account for 10% to 15% of cells found within the brain and are responsible for regulating brain development, maintenance of neuronal networks, and injury repair.

Analyzing brain tissues for studying HIV reservoirs is extremely difficult because these types of cells cannot be safely sampled in people taking ART. Therefore, for their study published in the Journal of Clinical Investigations, the researchers used the brains of macaques with the simian immunodeficiency virus (SIV), a virus that is closely related to HIV.

The researchers used physical separation techniques and antibodies to remove cells that were expressing microglial surface markers selectively. Then, they isolated and separated the highly pure brain myeloid cells from the CD4+ cells that were passing through the brain tissue. Past research has shown that latent HIV can hide within CD4+ cells that coordinate immune responses and are specifically targeted by the virus.

Using physical separation techniques, the researchers also obtained samples that were donated by four HIV+ people who are taking ART but suffering from other terminal illnesses.

Although the study has limitations, such as a small number of available samples from human donors, it supports the concept that microglial cells are a stable reservoir for dormant infection and can be targeted with potential treatments.

Getting closer to an HIV vaccine

An estimated 1.2 million people in the United States had HIV at the end of 2021. Of those, 87% were aware they had a disease. While there is no cure for HIV, it can be controlled with antiviral treatment. For most people, it helps to get the virus under control within six months and prevents further transmission.

HIV treatment comes in two forms: pills and shots. Pills are recommended at the beginning of the treatment and are taken every day. Meanwhile, people with viral suppression (having less than 200 copies of HIV per milliliter of blood) or an undetectable viral load for at least three months may consider shots that are given once a month or once every other month.

Although there is still a long way to find a cure for HIV, researchers are working on improving its prevention. In the 2022 Phase 1 clinical trial, an HIV-vaccine candidate induced antibodies against the virus in 35 out of 36 participants. However, it remains unclear if the vaccine could protect against HIV.

Throughout history, five people — all cancer patients — have been cured of HIV. They all received transplants with the rare genetic mutation, homozygous CCR5 Delta 32, that hampers HIV’s ability to infiltrate immune cells and is present in only 1% of the population. Researchers say that this approach shows promise in curing HIV outside of cancer patients.

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