Promising HIV vaccine proves ineffective

NAIROBI — A vaccine trial against HIV in South Africa has proven ineffective, prompting the National Institute of Allergy and Infectious Diseases to stop it. Scientists were cautiously optimistic about the trial, which involved 5,407 HIV-negative volunteers at 14 sites across South Africa.

The announcement made on Monday underscores the difficulty involved in creating a vaccine for sub-Saharan Africa, which has the highest HIV epidemic in the world, according to Dr. Larry Corey, principal investigator at the HIV Vaccine Trials Network, headquartered at the Fred Hutchinson Cancer Research Center, which conducted the trial.

The trial, called HVTN 702, began in 2016, with results expected in 2022. The vaccine research community had “great hopes” about positive outcomes from the trial and this news is a “significant setback,” to the field of HIV research, according to Linda-Gail Bekker, chair of the Global HIV Vaccine Enterprise Advisory Group.

“An HIV vaccine is essential to end the global pandemic, and we hoped this vaccine candidate would work. Regrettably, it does not,” said NIAID Director Dr. Anthony Fauci in a press release.

The HVTN 702 trial aimed to build off the successes of a 2009 trial in Thailand. That trial found, for the first time, that a vaccine provided protection against HIV. But the protection wasn’t high enough and the duration of the protection wasn’t long enough to bring it to market. In efforts to improve these variables, researchers launched HVTN 702.

“It’s very clear that the bar required to make a vaccine for the epidemic in South Africa is higher than it was in Thailand,” Corey said on the phone to Devex.

In Thailand, in the baseline studies, the rate of new infections was about 0.3% per year, whereas it was about 4.2% for women in South Africa, he said.

It will take time for researchers to know exactly why the HVTN 702 vaccine wasn’t effective, but hypotheses include that the HIV exposure rate is higher in South Africa than in Thailand, people come into contact with HIV more frequently, people have higher viral loads and the clade — or strain — of HIV found in South Africa is different to that found in Thailand, he said.

Moving forward, there is also a need to better understand the transmission dynamics for women — who have much higher incidence rates than men, he said.

“That’s one of the insights that comes from this vaccine trial,” he added.

Developing an HIV vaccine has perplexed researchers since the 1980s because of the complexity of the virus — it has high levels of mutations and different strains are found globally. If a successful vaccine is found, it will be the most complicated vaccine the world has ever seen, according to vaccine researchers.

 “I think this result today is a really important reminder of just how hard it is to develop an HIV vaccine,” Mitchell Warren, executive director at AVAC, an international non-profit focused on development and delivery of HIV prevention tools, told Devex on the phone.

The HVTN 702 study involved 5,407 HIV-negative sexually active men and women aged 18 to 35 years who either received the vaccine regimen or placebo injections. In an interim analysis of data on Jan. 23, it found that 129 HIV infections occurred among the vaccine recipients and 123 HIV infections occurred among placebo recipients — meaning the vaccine was ineffective.

The study was part of the Pox-Protein Public-Private Partnership which includes NIAID, the Bill & Melinda Gates Foundation, South African Medical Research Council, the HIV Vaccine Trials Network, Sanofi Pasteur, GlaxoSmithKline and the U.S. Military HIV Research Program.

“It is disappointing. But it was an important study that had to be done. There was a positive result back in 2009 and we had to follow the leads and follow the science. Now, the science is telling us this is not the direction that is going to get us to an HIV vaccine,” Warren said.

Luckily, this wasn’t the only ongoing vaccine trial.

There are three other late-stage vaccine trials. Two of them, called Imbokodo and Mosaico, use a “mosaic” approach aimed at protecting against a wide variety of global HIV strains. They are sponsored by Janssen Vaccines & Prevention. Results for Imbokodo are expected in 2021.

From these trials, “the early research looks promising,” Warren said.

There is also a trial examining the effectiveness of combining an HIV vaccine with pre-exposure prophylaxis — which is a daily pill used to prevent HIV.  

In addition to the vaccine trials, there are advanced clinical trials examining whether a broadly neutralizing antibody can prevent HIV.

“We have multiple approaches and we are pursuing parallel tracks, because developing a vaccine is so important,” Corey said. “I haven’t lost my cautious optimism. This one is disappointing — but I still have cautious optimism.”