The global fight against the human immunodeficiency virus is poised to make important advances thanks to three experimental HIV vaccines that are entering the final stages of testing at sites across the globe.
While any of these three late-stage HIV vaccine trials — known as HVTN 702, Imbokodo and Mosaico — could fail, scientists say they are more hopeful than at any time since 1984, when Secretary of Health and Human Services Margaret Heckler raised hopes by predicting that there would be a test-worthy HIV vaccine within two years.
This is “perhaps one of the most optimistic moments we have been in,” said Dr. Susan Buchbinder, director of the Bridge HIV research program at the San Francisco Department of Public Health and a chair of both the Imbokodo and Mosaico trials.
“We have three vaccines currently being tested in efficacy trials,” she said, “and it takes quite a bit to actually be promising enough in the earlier stages stages of trials to move you forward into an efficacy study.”
The oldest ongoing HIV vaccine trial, known as HVTN 702, is based on a prior vaccine candidate, RV144, that was effective, but not effective enough. In 2009, the RV144 clinical trial released findings showing that the vaccine lowered the rate of HIV infections by about 30 percent. To this day, RV144 remains the only HIV vaccine that have ever demonstrated any efficacy against the virus.
HVTN 702, launched in South Africa in 2016, was the first vaccine trial approved after the failure of RV144. According to the National Institute of Allergy and Infectious Diseases, the modified vaccination regime “aims to provide greater and more sustained protection than the RV144 regimen and has been adapted to the HIV subtype that predominates in southern Africa,” also known as HIV-1 clade C.
While RV144, at 30 percent effective, did not suffice for global distribution, it pointed the way forward for vaccine researchers, who adapted RV144’s successes to create HVTN 702. Buchbinder said even a partially effective vaccine would be “a tremendous breakthrough,” and “would really have the power to change the trajectory of the epidemic.”
Dr. Anthony Fauci, director of NIAID and a longtime advocate for a vaccine that is at least 50 percent effective, said he feels “even more strongly now” that a partially effective vaccine would be worth deploying. He said that is because prevention strategies like pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) “are being so successfully used, even in the absence of a vaccine, that if one or more of these vaccines look good, have a 50-60 percent efficacy, I think that’s going to be the game changer for turning the epidemic around.”
HVTN 702 completed enrollment this summer, and clinical results are expected in late 2020 or early 2021.
Imbokodo, the second trial, began in five southern African nations in 2017 and completed enrollment of 2,600 women this summer. In southern African nations, heterosexual women are at extremely high risk of HIV infection.
“It’s almost unbelievable, but it’s true, women between the ages of 18 and 25 — the prevalence of infection is well over 50 percent,” Fauci said. “If ever you wanted to get a population that, if the vaccine works, you’re going to know pretty quickly, then you want to go in women.”
Unlike HVTN 702, Imbokodo uses “mosaic” immunogens, which are “vaccine components designed to induce immune responses against a wide variety of global HIV strains,” according to the National Institutes of Health.
“The presumption is that a mosaic is going to give you broader coverage,” Fauci said.
In November, the third vaccine trial, Mosaico, marked its informal start after the first study participant received an injection. Mosaico is based on Imbokodo’s unique mosaic immunogen approach.
Imbokodo and Mosaico are largely identical and consist of six injections, with slightly different vaccine formulations administered during the final two clinic visits.
In addition, while Imbokodo is only being tested in African women, Mosaico will recruit 3,800 gay men and transgender people for its clinical trials at 57 sites in the United States, Latin America and Europe. For any HIV vaccine, Fauci said there’s a need to prove it works in different at-risk populations.
Imbokodo completed enrollment of study participants this summer, marking the formal end of the recruitment process. Results from Imbokodo are expected in 2021, and results from Mosaico are expected in 2023.