World’s AIDS Day 2016 brings especially hopeful news: A large-scale clinical trial has opened in South Africa to test an experimental HIV vaccine regimen that could lead to the first licensed vaccine against the virus that causes AIDS.
The experimental vaccine under study is a modified version of the so-called Thai vaccine, which in 2009 became the only vaccine tested so far to show even modest protection against the rapidly mutating virus that has killed 35 million people worldwide since the HIV/AIDS pandemic began in 1981.
The new trial, called HVTN 702, is funded by the National Institute of Allergy and Infectious Diseases, or NIAID, the Bill & Melinda Gates Foundation, and the South African Medical Research Council and conducted by the NIAID-funded HIV Vaccine Trials Network, or HVTN, a global network headquartered at Fred Hutchinson Cancer Research Center.
“The people of South Africa are making history by conducting and participating in the first HIV vaccine efficacy study to build on the results of the Thai trail,” said trial chair Dr. Glenda Gray, president and executive officer of the South African Medical Research Council, in a statement released by NIAID. “If an HIV vaccine were found to work in South Africa, it could dramatically alter the course of the pandemic.”
Gray is an HVTN co-director and head of its Africa programs. Co-chairing the trial with her are South African scientists Dr. Linda-Gail Bekker, deputy director of the Desmond Tutu HIV Centre at the University of Cape Town and chief operating officer of the Desmond Tutu HIV Foundation; Dr. Fatima Laher, a director of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital in Soweto; and Dr. Mookho Malahleha, deputy director of Setshaba Research Centre in Soshanguve.
It seems especially fitting that the four scientists leading the trial are women from Africa. Globally, women make up half of the 36.7 million people living with HIV, and 80 percent of infected women live in sub-Saharan Africa, the region hardest hit by the pandemic. Most infections in sub-Saharan Africa are transmitted heterosexually. For biological, socioeconomic and cultural reasons, women are more vulnerable than men to acquiring HIV during sex.
In a culture in which men dominate relationships, women often can’t negotiate safer sex practices such as condom use or taking a daily antiretroviral pill known as PrEP to prevent infection. One of the appeals of a vaccine is that it can be used discretely, without a woman’s partner even knowing.
“An HIV vaccine is the ultimate female prevention tool,” Gray said at a press conference at the recent international AIDS 2016 conference in Durban, South Africa. “You put it in your arm and it works in your vagina."
Conducted at 15 sites across South Africa, HVTN 702 will enroll 5,400 HIV-negative men and women between the ages of 18 and 35. Half will be randomly assigned to receive five injections of a two-vaccine regimen over a year and the other half will receive a placebo, then followed for an additional two years. Results are expected by late 2020.
Because it is unethical to deliberately expose people to HIV, testing to see whether a vaccine provides protection involves waiting several years and seeing how many people become infected naturally despite the prevention counseling and tools that will be offered to all trial participants.
The 2009 Thai study was widely considered a turning point in HIV vaccine research after decades of disappointment. Participants who received the vaccine, named for the country in which it was tested, had a 31 percent lower risk of becoming infected with HIV 3½ years after vaccination, compared to placebo recipients. Although not enough protection to warrant licensing, it showed for the first time that a protective vaccine against HIV was even possible.
The protection provided by the Thai vaccine took years of study to understand. This first, if modest, success allowed scientists for the first time to identify “correlates of protection,” or early signs of whether a vaccine might be effective.
The regimen being tested in the new trial has been altered to be more protective, longer-lasting and effective against the predominant HIV subtype in South Africa, which has the largest HIV epidemic in the world.
Public health experts generally want a vaccine to protect at least 70 to 80 percent of people vaccinated, but government regulators have said they would consider licensing an HIV vaccine if it protects at least 50 percent of those who receive it.
Even as scientists hope for at least a partially protective vaccine that would help in areas where infection rates — and thus the risk of infection — are highest, they are continuing the search for a vaccine that would be more effective. Even as it rolls out HVTN 702, the HVTN has begun investigating a second path to an HIV vaccine. Partnering with a sister network, the HIV Prevention Trials Network headquartered in North Carolina, it launched a clinical trial earlier this year on an approach called antibody mediated prevention, or AMP. Two parallel AMP clinical trials will eventually involve more than 4,000 participants in the United States, South America and southern Africa.
Rather than delivering a vaccine, the AMP trial uses an intravenous infusion to deliver so-called broadly neutralizing antibodies (or a placebo) to trial participants. If the experimental antibodies being tested in the AMP trial provide protection as hoped, information gleaned from the study could help scientists figure out how to reverse-engineer a vaccine to elicit the antibodies at the concentrations needed. The path to the promised land of a vaccine that is 80 percent to 90 percent effective may well end up combining the two approaches.
The excitement over HVTN 702 — along with the first study of broadly neutralizing antibodies that could someday complement a vaccine — was palpable at the AIDS conference in Durban.
“If we are successful in South Africa, there will be bridging studies to anywhere in the world — to East Africa, the U.S., to young girls, to babies,” Gray said at the time. “There is going to be an explosion of information around HIV. This is what we — all of you — have worked our whole lives for. We are very privileged to be part of the next five years.”
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Mary Engel is a former staff writer at Fred Hutchinson Cancer Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.
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