Three late-stage HIV vaccine trials—known as HVTN 702, Imbokodo and Mosaico—which are poised to make important advances against the human immunodeficiency virus (HIV) are entering the final stages of testing at sites across the globe.
The oldest ongoing HIV vaccine trial, known as HVTN 702, is based on a prior vaccine candidate, RV144, which 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 has ever demonstrated any efficacy against the virus.
Launched in South Africa in 2016, HVTN 702 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. The vaccines do not contain HIV and therefore do not pose any danger of HIV infection to study participants.
“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,” said Dr. Anthony Fauci, director of NIAID and a longtime advocate for a vaccine that is at least 50 percent effective.
“Imbokodo” is the Zulu word for “rock,” which is part of a well-known proverb in South Africa that refers to the strength of women and their importance in the community. “The rapid progress we have seen with women enrolling in Imbokodo is impressive, and a sign that the world’s quest to find an HIV vaccine is accelerating,” said Professor Glenda Gray, CEO and President, South African Medical Research Council (SAMRC), and a chair of the Imbokodo study. “I’d like to pay tribute to the 2,600 women who have volunteered to participate in Imbokodo. They are the true heroes in this effort.”
Unlike HVTN 702, Imbokodo and Mosaico use “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 regimen is delivered through a heterologous vaccination schedule, involving four to six immunizations given over one year. By using different vaccine components for vaccinations one and two, as compared to vaccinations three and four, the goal is to produce strong and long-lasting immunity to HIV.
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.
HVTN 702 is fully underway, with 5,407 participants, but results will not be analyzed until the trial is completed in late 2022. 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.
If these vaccine trials all fail, public health officials say enough tools currently exist to stop the spread of HIV—if only people would, or could, use them.
PrEP, a daily pill that prevents HIV infection, is safe and effective, but can be expensive and not enough people are using it to slow HIV transmission and end the epidemic. And successful treatment of people living with HIV results in an undetectable viral load, such that they cannot transmit the virus via sexual activity, which is known as “treatment as prevention” or TasP.
“It goes exactly to what I have been saying for years and years—if you implement the tools that you have, you will definitely see an impact on the dynamics of the epidemic,” Fauci said. So, if one of the three vaccines currently being tested works, “that would be the endgame,” he said.