Researchers are investigating whether an antibody used to treat Crohn’s disease could also help suppress HIV, based on a study done in monkeys published Thursday.
The drug, vedolizumab, appears to have reduced simian immunodeficiency virus, or SIV, to virtually undetectable levels in infected macaques and kept them there for two years, even after they were taken off of antiretroviral therapy, or ART, said senior author Aftab Ansari.
“These monkeys are basically controlling the virus themselves,” said Ansari, a pathologist at Emory University.
The study, published in the journal Science, reported generally undetectable levels of SIV up to nine months after the monkeys given vedolizumab stopped ART, but the scientists have continued to follow them. And now, researchers at the National Institute of Allergy and Infectious Diseases are recruiting up to 20 people for an early-stage clinical trial using a similar protocol: taking the patients off ART and treating them with vedolizumab, sold commercially as Entyvio.
The researchers will be investigating whether the combined treatment is safe and controls HIV levels.
Outside scientists said the study was very exciting, but they and the study’s authors all cautioned that what works in a monkey does not necessarily work in a person.
“It provides a pretty reasonable rationale that it should be looked at as a potential way to augment the health of people with HIV,” said David O’Connor, the chair of the Wisconsin National Primate Research Center’s global infectious disease division and a University of Wisconsin professor, who was not involved with the study.
Another caveat: The monkeys had only been infected for five weeks when they were first treated with ART. It is generally easier to control viral levels if someone has been infected for a short time, outside scientists said, but sometimes patients have HIV for years before they start ART.
ART has been the gold standard in HIV treatment for many years and has helped turn HIV from a death sentence into a chronic condition by preventing the virus from replicating. But in addition to the annoyance of having to take it daily, ART is toxic. Patients can suffer side effects such as chronic inflammation and the early onset of age-related diseases, and the drugs can lose effectiveness over time. Scientists have wondered if somehow, once ART brings viral levels down, the treatment could be stopped without a resurgence of the virus.
For the study, the researchers focused on 15 rhesus macaques that started a 90-day course of ART five weeks after being infected with SIV. Nine weeks after infection, eight of those macaques received the first of eight infusions of the monkey version of vedolizumab, given once every three weeks. The other monkeys received a control antibody. All treatment ended after 32 weeks.
After the ART was stopped, the viral levels in the monkeys that received the control antibody rebounded within a few weeks. Some of the monkeys that received vedolizumab saw some initial uptick in their viral load after ART was stopped, but those levels quickly fell. For the rest of the study, all the monkeys given vedolizumab had undetectable viral levels or brief blips of the virus, the researchers reported.
Vedolizumab, which is also approved to treat ulcerative colitis, targets a receptor found on immune cells that HIV and SIV infect called alpha-4 beta-7 integrin. The antibody could be preventing the immune cells from sticking to gastrointestinal tissues, a place where SIV and HIV both replicate like crazy. But the researchers are not sure how that roadblock could keep the virus on the defensive, or if indeed it is that process that is tamping down viral levels. Those are among the questions they are trying to answer with additional studies.
“We still are not 100 percent sure of what the mechanisms are, and we’re not 100 percent sure of what the implication will be in humans,” said Dr. Anthony Fauci, director of the NIAID, who co-led the study.
The study also found that the vedolizumab-like antibody appeared to help a type of immune cell, called a CD4+ T cell, rebound to pre-infection levels. The virus wipes out many of those cells, which help rally the immune system to fight off pathogens, and they do not fully recover even when a patient is on ART, the authors said.
Outside researchers said the immune cells might have been more likely to bounce back because the monkeys started treatment so quickly, meaning the virus did not have long enough to deplete those cells.
For some time, researchers have been investigating whether antibodies, proteins the immune system uses to recognize and attack pathogens, could help control HIV, said Richard Harrigan, director of research laboratories at the British Columbia Center for Excellence in HIV/AIDS, who was not involved with the new research.
“What’s kind of unusual is this worked,” at least in monkeys, he said about the study.