Herald
Yet another seemingly promising HIV vaccine has failed clinical trials.
The vaccine is “essential to ending the global pandemic,” according to Anthony Forch, who is responsible for the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health who was conducting the trial.
But the latest mistakes, though disappointing, are not surprising.
It’s helpful to go back to the beginning to understand why.
About 12 years ago, two studies on a vaccine candidate known as MRK-Ad5 were discontinued.
The failure was comprehensive. Studies in STEP (registering men and women in the Americas, Caribbean, and Australia) and Fambili (including men and women in South Africa) found that MRK-Ad5 failed to protect subjects from HIV infection.
To make matters worse, there was evidence that it might have been more likely to be infected with HIV, the virus that causes AIDS.
But the following year, expectations rose again as another clinical trial, known as RV 144, appeared to show modest positive results in Thailand.
Still, the conclusion that the vaccine worked was based on a somewhat questionable statistical analysis.
In fact, of 125 HIV-infected (initially HIV-negative) study participants (402 of 16 total), 74 received placebo and 51 received the vaccine.
This equates to an effective rate of 31.2% — a good starting point, but not close to the level needed to tackle the public health challenge of the magnitude of the epidemic of HIV in sub-Saharan Africa.
A closer look at the results shows that they are weaker than they look.
As observed by former professor Ronald Desrozier at Harvard Medical School in 2017, the HIV acquisition curve for the placebo group was not linear, leading to a surge in placebo recipient acquisition in the first year of the trial.
That “abnormal” increase accounts for “most or all of the differences in acquisition” compared to the vaccinated.
In other words, the fact that more HIV-infected placebo patients were associated with less protection than those who were vaccinated.
In addition, Desrosiers argued that if the vaccine had a protective effect, infected vaccinated people would have a lower viral load than non-vaccinated people.
It wasn’t.
Nonetheless, some researchers have tested vaccine candidates based on the RV 144 candidate, but with encouraging results to advance the recent South African trial HVTN 702, which has adapted to the most famous HIV strain in the country. I examined.
Eighteen months later, 129 of 5400 vaccinated participants were infected compared to 123 who received placebo.
The result was a devastating blow for millions of Africans, who wanted researchers to finally approach a long-term solution to the AIDS epidemic.
However, the results of the Thai trial were not strong enough to justify such a large and expensive clinical trial.
This does not mean that test results worthy of further study must be overwhelmingly positive.
But, as Desrosiers emphasizes, spending hundreds of millions of dollars to manufacture and test a product that has little reasonable promise of effectiveness is at best a waste.
More comprehensive basic and preclinical research will help scientists identify approaches that are far more likely to succeed.
In the case of RV 144, a small interim trial could have allowed researchers to determine if it was worth investing in another large trial at a much lower cost.
The remaining funds may have been directed to other mitigation strategies for HIV / AIDS, including basic research.
Fauci is the correct answer. Vaccines are essential to ending the spread of HIV in sub-Saharan Africa.
However, this is a long-term solution and we do not yet have the knowledge to deserve a very expensive and large clinical trial.
Small-scale human trials are more appropriate at this time because they can be scaled up if they have been shown to work convincingly. Vulnerable and infected people, on the other hand, need other types of support, from education to treatment.
As exciting as it looks, pi-in-the-sky ideas, or even “intelligent” guesses, aren’t good reasons to sacrifice the health and well-being of people today.
Denis Chopera is a Medical Virologist and Program Executive Manager at the Sub-Saharan African Network of TB / HIV Research Excellence (SANTHE) based in the African Health Institute. He is an Aspen New Voice Fellow (2018) and an African Century Fellow (2019-2020).
