Results of ‘truly disappointing’ HIV vaccine trial published
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Researchers published data from a late-stage clinical trial of a once-promising HIV vaccine candidate more than a year after the trial was stopped early because the vaccine was not preventing infections.
The researchers found almost identical rates of infection among patients in the HVTN 702 trial whether they received the HIV vaccine regimen or placebo.
“The high HIV-1 incidence that we observed in our trial illustrates the unrelenting aspect of the epidemic, especially among young women,” HVTN 702 Protocol Chair Glenda E. Gray, MBBCH, FCPAED, president and CEO of the South African Medical Research Council, and colleagues wrote in The New England Journal of Medicine. “More than ever, an effective vaccine to prevent HIV-1 acquisition in diverse populations is needed.”
Gray and colleagues enrolled 5,404 HIV-negative adults in South Africa to test a vaccine based on a regimen that was found to be around 31% effective during the RV144 vaccine trial in Thailand more than a decade ago. The researchers randomly assigned participants in the new trial to receive either the vaccine regimen — injections of a canarypox vector-based vaccine called ALVAC-HIV during months 0 and 1, followed by four booster injections of ALVAC-HIV with the bivalent subtype C gp120-MF59 adjuvant during months 3, 6, 12 and 18 — or a placebo.
A total of 2,704 adults received the vaccine, and the remaining 2,700 received a placebo. The study’s primary outcome was HIV-1 infection between randomization and 24 months.
According to the results, there were 138 infections in the vaccine arm and 133 in the placebo arm (HR = 1.02; 95% CI, 0.81-1.3).
The researchers wrote the one of the study’s major limitations was an inability to compare the regimens used in the RV144 trial — which produced only short-lived CD4 and T cell responses — and HVTN 702 trial.
“Additional studies on the immunologic characteristics and viral sequences are under way to improve our understanding of the results and implications for this field of research,” Gray and colleagues wrote. “Isolating which factor or combination of factors is responsible for the different efficacy results in the two trials will be challenging, given the differences between the vaccines and the immune responses they generated, along with the differences in the levels of viral exposure, the extent of matching between the vaccines and the exposing viruses, and in host genetics and other host factors.”
Perspective
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The world needs an effective HIV vaccine. This remains the case more than 3 decades following the discovery of HIV and promises of the delivery of a vaccine within 2 years made at the first international AIDS conference in 1985. Despite an enormous (and expensive) effort, only one candidate vaccine trial, RV144, conducted in Thailand and published in 2009, has reported even modest efficacy. The current trial in South Africa was in part based on that earlier work but with additional elements aimed at increasing benefit in preventing infection in a region with high prevalence of HIV subtype C and a much higher background HIV incidence. The trial (ALVAC-HIV and Bivalent Subtype C gp 120-MF59) enrolled more than 5,400 young, uninfected adults. Half received the active vaccine, and the rest were given a placebo. They were then followed for new cases of HIV infection. Despite preliminary evidence in earlier small trials of immunogenicity of this approach, the current trial was definitively negative. The numbers becoming infected in each group were nearly identical, and postinfection viral loads were not reduced in the active vaccine recipients. This is truly disappointing and underscores the urgent need to continue to facilitate access to ART and PrEP of all types and other prevention strategies while we continue the search for an effective vaccine. Given the remarkable success in SARS-CoV-2 vaccine development and newer technologies used in that effort, we can remain hopeful. But this is not an encouraging development.
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