By TAMAR KAHN
In a blow to global HIV vaccine research, scientists have halted a large SA trial testing an experimental shot, after a routine review found it does not work. There is no evidence it caused any harm.
More than 35 years after the virus was first identified, there is still no cure for HIV, and an effective vaccine remains elusive.
Nowhere is the need more pressing than in SA, which has the world’s greatest HIV burden. More than 7.7-million people were living with the disease in 2018, according to UNAids.
The HVTN 702/Uhambo study, funded by the US National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation, was designed to test a modified version of the 2009 Thai RV155 vaccine, the only one to date to provide some protection against the virus, in the hope that the adaptations would yield a better result.
The HVTN 702 trial began in 2016, testing a shot modified to tackle the dominant strain of HIV circulating in SA, clade C. Participants were also given booster shots to try and prolong the protection seen in the Thai study.
A small precursor trial, called HVTN 097, that tested the candidate vaccine in 100 SA volunteers in 2013, found it stimulated an immune response.
But a routine, interim review of the HVTN 702 study conducted by an independent data safety monitoring board on January 23 2020, found the experimental shot did not provide any protection against HIV.
The analysis examined how many participants were diagnosed with HIV after at least 60% of them had been in the trial for at least 18 months, and found 129 infections occurred among the vaccine recipients and 123 among those who got a placebo. More than 5,400 volunteers were enrolled in the trial at 14 sites in SA.
The study’s protocol chair, Medical Research Council president Glenda Gray, said the results were not only disappointing for the field of vaccine research, but also sounded a warning about the state of SA’s HIV epidemic. The review found extremely high rates of HIV transmission among participants, who had all been offered the best HIV prevention measures currently available — regular counselling and testing, free condoms and lubricant, and free pre-exposure prophylaxis.
The trial found HIV incidence of up to 4% among women, she said.
“This trial tells me our epidemic is out of control [and] we have no understanding of the dynamics of transmission,” she said. The results also suggested that contrary to expectations, SA’s massive HIV treatment programme had not reduced the amount of virus circulating in the population, she said.
Wits health consortium HIV researcher Francesca Conradie, who was not involved in the trial, said the high HIV infection rates were worrying, and suggested current prevention strategies were not working.
Scientists have yet to determine why the candidate vaccine failed.
“We think there are a couple of reasons why it didn’t work. One is that the force of infection in SA is 14 times that of Thailand and this regimen was just not able to withstand the attack rate. Maybe what we had was a pellet gun and we needed a bazooka,” said Gray.
“Secondly, maybe we don’t understand the dynamics of clade C. It is the predominant clade for a reason, and maybe we haven’t appreciated that fully,” she said.
Further analysis was planned to examine whether genetics played a role in how participants responded to the experimental vaccine, she added.
“An HIV vaccine is essential to end the global pandemic, and we hoped this vaccine candidate would work. Regrettably, it does not,” said Anthony Fauci, director of the NIH National Institute of Allergy and Infectious Diseases.
“Research continues on other approaches to a safe and effective HIV vaccine, which I still believe can be achieved,” he said.