The infection that causes HIV, the AIDS virus, is in most cases incurable. Only four people in the world have been completely cured, and because of the most dangerous treatment such as a special bone marrow transplant is indicated in the treatment of his cancer. The flaw is that HIV does not die with so-called virus reservoirs, sanctuaries where HIV hides from treatments.
In order to develop treatments that can completely eliminate HIV infection, scientists need to identify not only all the places where the virus can hide its genetic code, but also how to target them.
Now, in research using blood samples from HIV-infected men and women for long-term suppression therapy, a team led by Johns Hopkins Medicine scientists provides new evidence that such a stable reservoir of HIV genomes appears to be located in circulating white blood cells. it is called monocytes.
Monocytes are short-lived immune cells that are precursors to macrophages, immune cells that engulf viruses, bacteria, and other foreign cells from the host.
In a study now published in Nature Microbiology, the researchers found that blood samples from people with HIV undergoing long-term standard antiretroviral therapy contained monocytes, which can infect the host’s stable HIV DNA into neighboring cells.
Writing these findings in a paper may provide a new way to improve therapies and eventually cure HIV, which affects more than 34 million people worldwide, according to the World Health Organization. Current antiretroviral drugs can successfully suppress HIV to almost undetectable levels, but have not resulted in the integrity of the virus.
“We do not know how these monocytes and macrophages are involved in the eradication of HIV, but our results suggest that we should continue this line of research to understand their role in this disease,” says Janice Clements of Johns Hopkins University.
Scientists have long known that HIV hides its genome most often in a type of immune cell called a CD4+ T cell. These hiding places are known as sanctuaries.
“To eradicate HIV, the goal is to find biomarkers in the cells that harbor the HIV genome and kill the cells,” explains Professor Rebecca Veenhuis.
To investigate the role of monocytes and macrophages in the blood circulation as HIV receptors, the scientists obtained blood samples between 2018 and 2022 from 10 HIV positive people who had been on antiretroviral treatment for years.
First, blood cells are extracted from the samples and the cells are grown in the laboratory. Monocytes typically transform very quickly, at least three days, into macrophages, producing monocyte-macrophage derivatives.
To eradicate HIV, the goal is to find biomarkers for cells that receive the HIV genome and kill the cells.
Rebecca Veenhouse
Johns Hopkins University
All 10 had detectable HIV DNA in their monocytes, macrophages, but at levels 10 times lower than those found in their CD4+ T cells, now known as the HIV reservoir.
Next, to determine whether HIV genomes were present in monocytes prior to macrophage differentiation, an experimental team was used to detect complete HIV genomes in monocytes.
Thus, blood samples were used from another group of 30 people (eight men from the first group and 22 women) with HIV, also treated with standard antiretroviral therapy. They found HIV DNA in the CD4+ T cell monocytes of all participants.
In addition, they were also able to isolate HIV-infected monocytes from half of the research participants. Virus extracted from these cells was able to infect CD4+ T cells.
Three of the participants had their blood tested multiple times over a four-year period, and each day the scientists found HIV DNA was infectious and carried by monocyte-derived macrophages. “These results suggest that monocytes are a stable reservoir of HIV,” says Clemens.
