Myeloid Cells can Harbor HIV in People on ART

A new study has found that myeloid cells (a subset of white blood cells), can maintain HIV cells in people who have been virally suppressed for years on antiretroviral therapy (ART), and can be reactivated and infect new cells.

“Yes, the cells are short-lived, but our follow-up data show that HIV can persist in monocytes over several years in people who are virally suppressed. The fact that we can detect HIV in these cells over such a long period suggests something is keeping the myeloid reservoir going,” said study author Rebecca Veenhuis, PhD, an assistant professor of molecular and comparative pathobiology and of neurology at Johns Hopkins University School of Medicine.

The study was published in the Nature Microbiology.

These cells, the short-lived monocytes and longer-lived monocyte-derived macrophages, were previously believed to not hold any value in finding potential cures. “Our findings challenge the prevailing narrative that monocytes are too short-lived to be important in cure efforts,” Veenhuis said. Monocytes are immune cells that circulate in the blood for about 3 days before traveling to tissue in various parts of the body, including the brain, where they can mature into macrophages. It has not been determined whether latent HIV in these cells can become active again and infect other cells.

“What’s really important in the long run is understanding how monocytes contribute to the tissue macrophage reservoir,” explained Janice Clements, PhD, senior author on the study and professor of molecular and comparative pathobiology at Johns Hopkins University School of Medicine. “If monocytes can carry virus to the brain, or lung, or another part of the body and infect resident macrophages that are self-renewing and live almost indefinitely, that’s a real problem.”

The investigators measured HIV DNA in myeloid cells in a sample of 30 participants with HIV that were virally suppressed and had been on ART for at least 5 years. They found detectable levels of HIV genetic material in monocytes and macrophages, though the levels were much lower than those observed in CD4 T cells. In some participants, the HIV genetic material found in monocytes was intact, which suggests it may be capable of infecting other cells if reactivated.

They then used the new quantitative method they developed to directly measure viral spread from HIV found in myeloid cells. They isolated monocytes from blood samples taken from 10 participants and nurtured the monocytes in cultures that contained antiretroviral drugs, to replicate the participants’ baseline physical state. After the monocytes differentiated into macrophages, the researchers introduced an immune activating agent and then added fresh white bloods cells to allow for the virus to spread to new cells.

The investigators collected samples from the cell cultures several times over the next 12 days. They included checkpoints throughout the process to ensure that infected CD4 T cells did not interfere with their measurements. The results showed that cultures from five of the 10 participants had detectable HIV genetic material in monocyte-derived macrophages that could be reactivated to infect other cells and produce more virus. The participants who had these reactivatable reservoirs of HIV in monocyte-derived macrophages had higher overall levels of HIV DNA material.

The investigators noted a few limitations including the size of the study, and the need for greater population diversity to estimate the proportion of people who have latent HIV in myeloid cells.