HIV Vaccine Trials Network
It has taken more than 4 years and $119 million for HIV researchers to test whether giving people infusions of antibodies made in a lab can protect them from the AIDS virus. Now, the unsatisfying answer is in: sometimes.
People who were given infusions of the monoclonal antibodies every 8 weeks had a 75% lower risk of becoming infected with HIV—but only if they were exposed to strains of the virus that remained susceptible to the antibody. Researchers say the strategy, which they hoped would provide “passive immunity”—in contrast to the active immunity triggered by vaccines, none of which exist for the AIDS virus—is likely to be more successful with recently developed monoclonal antibodies that work against a broader swath of HIV strains.
The Antibody Mediated Prevention (AMP) trial consisted of two studies of people at high risk of HIV infection: one in 1900 women in seven countries in sub-Saharan Africa and another in 2400 men who have sex with men and transgender women in South America, Switzerland, and the United States. Half of them received an infusion of a powerful monoclonal antibody, selected from the blood of an HIV patient years ago, every 8 weeks for 20 months; the other half received placebo infusions. The subjects were tested for HIV every 4 weeks, and if they became infected, researchers took samples and analyzed how susceptible the virus was to the monoclonal.
As it turned out, 70% of the HIV strains circulating in the places where the trial took place were variants that the antibody had difficulty stopping in test tube studies. So overall, the trial found no benefit. People infected in the placebo group had an HIV strain that was susceptible to the antibody far more often than those infected in the treatment group, however. From this analysis, researchers were able to calculate the 75% reduction in infection risk if the monoclonal matched the local HIV strain.
The study’s results, presented today at the virtual HIV Research for Prevention Conference, are “challenging to message,” says Chris Beyrer, an epidemiologist at Johns Hopkins University’s Bloomberg School of Public Health who was not involved in the trial. But he is hopeful about newer monoclonal antibodies that have far more “breadth” against different HIV strains. “We always knew that both of these studies were proof of concept,” Beyrer says. “On the face of it, it looks like [the antibodies] didn’t work, but in fact … if the antibody is a good fit with the circulating virus, and the titer of the antibody is high enough, you get protection.”
Larry Corey, a University of Washington, Seattle, virologist and one of the trial’s principal investigators, calls the results “magnificent” because the monoclonal antibody could be used with more broadly neutralizing antibodies against HIV in a highly effective prevention cocktail. “It’s like having a narrow spectrum antibiotic at the moment,” Corey says. “There’s no reason we can’t use that to get cocktails that work against 95% of the viruses.”
When the trial started in 2016, researchers had discovered more potent antibodies against HIV that had more breadth, but study investigator Nyaradzo Mgodi, a pathologist at the University of Zimbabwe, says none was yet ready for testing in an efficacy trial. “We could have opted to wait for more powerful antibodies, or to conduct less ambitious studies that offer more limited advances to the field,” Mgodi wrote in an email. “Instead, in exploring an established concept of antibody prevention for infectious disease, and working to extend that concept to HIV, we advanced the HIV prevention field further and faster!”
A powerful biomedical HIV prevention strategy already exists, however: a daily antiviral pill known as pre-exposure prophylaxis, or PrEP, which some AMP participants took as well. Monoclonal antibodies would have little appeal if PrEP was widely and consistently used, but many people have difficulty or don’t like taking daily pills, and its efficacy in women may be lower than men. Injected, long-acting antiretrovirals have also worked as PrEP in clinical studies but have yet to be licensed; they might provide a cheaper alternative to antibody infusions.
Yet Corey says monoclonals may find a role in HIV prevention for people who are reluctant to take antiretroviral therapy. “The participants enrolled in the study were really enthused about the fact that this was a natural substance and it was sort of like, if there was a vaccine, this is the stuff that that my body would be making,” Corey says. He notes that over the 4 years of the trial, the study gave 46,000 infusions and participants only missed 4% of their appointments.
Several small-scale prevention trials with more broadly neutralizing antibodies are underway, but Corey says it may take 18 months before any of those are ready to begin a larger scale efficacy study.
Source: Science Mag