In a major step forward for HIV vaccine research, the U.S. research agency will partner with a pharmaceutical company on a large-scale, advanced-stage clinical study on an HIV vaccine. If the trial is successful, the vaccine may become the first ever to be approved for HIV prevention. But the rise of PrEP has created unexpected challenges to study enrollment.
The study, called Mosaico, will recruit 3,800 cisgender men and transgender people who have sex with men and/or transgender people in the United States, Latin America, and Europe. It is being conducted in collaboration with the HIV Vaccine Trials Network. It is being sponsored by Janssen Pharmaceuticals (the medical research arm of Johnson & Johnson) and the National Institutes of Health (NIH), and conducted in collaboration with the HIV Vaccine Trials Network.
Specifically, the Phase 3, randomized study will recruit from 55 sites in mostly urban locations in the United States, Mexico, Peru, Brazil, Argentina, Poland, Spain, and Italy. Enrollment in the trial will begin in 2020.
In the trial, the vaccine candidate will be given as an injection to people who are HIV negative at four different time points over 12 months. Critically, study sponsors say that patients who volunteer for the trial will be counselled on other HIV prevention options, including pre-exposure prophylaxis (PrEP).
"I think it's an interesting step in the right direction," said Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID) at NIH. However, he cautioned, "I generally don't get excited about things until I see the data."
"We still have a number of years to go," said Mitchell Warren, executive director of AVAC: Global Advocacy for HIV Prevention. "But for a field that has struggled for many, many years -- this vaccine matters."
Although scientists have been hunting for an HIV vaccine for the past three decades, their quest has remained elusive -- in part because the virus has evolved into multiple different strains that are clustered in different regions across the globe.
Two Similar HIV Vaccine Trials Will Run Concurrently
The excitement surrounding this vaccine has to do with the fact that it's a so-called "mosaic," comprised of multiple HIV variants and boosted with an HIV clade C protein, which is given as an additional injection alongside the last two shots.
"This [vaccine] uses snippets of HIV from around the world, and it's really done in a way that's trying to maximize coverage," said Susan Buchbinder, M.D., protocol chair for Mosaico.
"The hope would be to create a global vaccine that can work around the world, [instead of] boutique vaccines that only work in certain parts of the world," she said.
If data are positive, Mosaico could be used as a registrational trial for Food and Drug Administration (FDA) approval, Buchbinder said. This trial builds on other, smaller studies, including very promising animal data and two in-human studies called APPROACH and TRAVERSE.
A Phase 2b trial among at-risk women in Southern Africa is already underway. That trial uses a vaccine that is very similar to the vaccine used in the Phase 3 Mosaico trial, but it uses a slightly different clade C "booster," Buchbinder explained.
The Phase 2b trial, called "Imbokodo," has enrolled 2,600 sexually active cisgender women. Initial results are expected in 2021.
According to Warren, the fact that Janssen and the NIH have decided to launch the Mosaico trial before seeing the results of the Imbokodo trial is a testament to their faith in the experimental vaccine.
In addition, the fact that the research study has the backing of a pharma industry partner bodes well for the vaccine's uptake and commercialization, should it be approved, Warren said.
HIV Vaccine Research Trials in the PrEP Era
But as the sponsors ramp up their efforts to conduct a Phase 3 HIV vaccine trial -- the first of its kind in over a decade -- they have had to grapple with a new HIV prevention landscape in which people who are HIV negative now have access to an FDA-approved HIV prevention medicine.
"It makes it more complicated to do a [vaccine] study when PrEP is available," said Fauci. However, he said, it is possible to recruit patients to Mosaico in an ethical way.
"My experience with the many, many people that I've interacted with [is] there are some people who just don't like taking a pill every day" but still have a high risk of HIV, he said. Those would be ideal candidates for Mosaico.
Crucially, sponsors say that patients who wish to enroll in Mosaico will be presented with an "HIV prevention package," including PrEP. Those who express interest in the PrEP option will be referred to a PrEP clinic.
"That's partly why we have 55-plus sites that will be enrolling ... [and] we're placing navigators at each of the sites," said Buchbinder. "We know there will be challenges to finding this population, but we know this is the ethical way to move forward."
Though recruitment may take longer (with a number of volunteers presumably opting for FDA-approved PrEP rather than enrolling in the trial), Mosaico may have the dual benefit of potentially bolstering PrEP uptake in the United States, Warren said.
"The degree of difficulty is high," said Warren, but sponsors "have done a good job of starting to work with advocates and civil society groups."
Even in an era of PrEP, an HIV vaccine is desperately needed, Fauci said. He pointed out that, theoretically, the prevention strategies of undetectable equals untransmittable (U=U) and PrEP should be enough to end the epidemic.
But "we don't live in a theoretical world -- we live in the real world," he said, "and the real world experience tells us we still have enormous gaps."