Antiretroviral drugs have revolutionized the treatment of HIV, the virus that causes AIDS, but they’re not considered a cure. That’s because HIV can hide in the body in “reservoirs” that can resurge at any time. Hence much of the HIV research that’s happening today is focused on combating HIV reservoirs.
Scientists at the University of North Carolina at Chapel Hill are reporting progress in their efforts to use immunotherapy—a technology that’s most closely associated with oncology—to eradicate HIV reservoirs.
The technique involves collecting T cells from HIV patients, growing them outside the body to expand their population, then infusing them back into the body. The team’s plan is to combine the cells with drugs that make latent HIV reservoirs visible to the immune system, so the T cells can find the virus and kill it. But first they had to show that the first part of the process is well tolerated by patients—and they did, with a new study published in the journal Molecular Therapy.
The trial involved six patients with HIV who were taking antiretroviral drug regimens that had reduced their viral loads to undetectable levels. Each patient received two infusions of HIV-specific T cells over two weeks.
The treatment was well tolerated, the UNC team reported. What’s more, the researchers were able to measure an increase in antiviral activity in two of the patients, which they were able to link to the T cells. The research was supported by the National Institutes of Health.
The trial didn’t show a decrease in the size of the latent reservoirs, likely because it wasn’t powered to do so: The UNC team didn’t treat the patients with latency-reversing drugs, and the dosages of T cells they infused were low. Furthermore, they didn’t employ strategies for expanding the population of HIV-fighting T cells once they were infused back into patients.
“This paves the way for the next step, which is to combine this immunotherapy approach with latency-reversal therapy in order to wake up the HIV out of its latent state, where it is invisible to the immune system, then clear it out with the immunotherapy," said first author Julia Sung, M.D., assistant professor of medicine at UNC, in the statement.
T-cell therapies have generated a lot of enthusiasm in the cancer world, thanks largely to the recent FDA approvals of two such treatments for blood cancer, Novartis’ Kymriah and Gilead’s Yescarta. But early efforts to apply the technology to HIV failed to produce a therapeutic response.
The UNC researchers showed in previous studies that they could take cells from HIV-infected patients and use them to clear latent cells by exposing those cells to Zolinza, a chemotherapy drug that’s known to be able to reverse latency.
It’s one of several approaches being tested for eliminating HIV reservoirs. In April, a team at the Fred Hutchinson Cancer Research Center reported promising results from an animal trial involving stem cells that were edited to include a mutation in the gene CCR5, which is known to be involved in HIV resistance. When the cells were put back into macaques infected with simian/human immunodeficiency virus (SHIV), an illness that’s related to HIV, virus reservoirs shrank.
Teams from the Salk Institute and Temple University have used CRISPR gene editing in different ways to remove some latent HIV from cells and prevent what’s left from resurging at a later time.
UNC is now enrolling patients in a study that will combine Zolinza with their own HIV-specific T cells. The participants will receive 20 doses of chemotherapy and five infusions of T cells. The researchers hope to complete the study in 2021.