We need an HIV vaccine – but should large scale clinical trials be our priority?

Thursday, 1 March, 2018

Dr Denis Chopera, SANTHE Programme Executive Manager

As HIV experts gather for a major global conference in Boston this week (editor: March 4-7) in Boston, it takes me back to 10 years ago when I watched respected Harvard professor, Dr Ronald Desrosiers, give a plenary talk at the same conference and same venue. This was soon after the STEP vaccine trial which, instead of protecting people from HIV, was found to have increased their infection risk by 41 percent.

This was a dark moment for the HIV research community as many had high hopes that the STEP vaccine would work. Yet I fear we might not have learned from our past mistakes.

Desrosiers stressed that the failure should have not come as a surprise given that clinical trials carried out in monkeys had not shown convincing protection from infection. He criticised the use of large amounts of money "to manufacture and test products with little reasonable hope of efficacy". Nearly US$200 million had been spent on the STEP clinical trial, and even more on product development.

However, the failure of the STEP vaccine trial did not dissuade researchers from continuing to hunt for a vaccine. And 10 years and billions of dollars later, Desrosiers’ criticism still looms large: “Are human vaccine trials the best use of resources?” In Africa, where I live and work, the question is particularly acute in the face of declining resources.

UNAIDS reported a 7 percent decline in donor funding for the fight against HIV in poor and middle-income countries between 2015 and 2016. This was the second successive year of decline and is the lowest funding level since 2010.

A lot of progress has been made in HIV prevention strategies as well as in understanding the virus. Since 2000, the global response to HIV has averted 30 million new infections and nearly eight million AIDS-related deaths, according to UNAIDS

However, on the vaccine front, one essential piece of the puzzle is still missing. That is, we still do not know how to prompt a person’s immune system to create their own antibodies which can protect against HIV – known to scientists as “broadly neutralizing activity” – using a vaccine.

Conventional vaccines activate the body’s immune system to recognize and destroy disease-causing agents such as viruses and bacteria. But because the HIV virus changes rapidly, an ideal vaccine would need to cause the recipient to create antibodies which are effective despite those many changes, or “broadly neutralizing”. As scientists continue to grapple with this challenge, several HIV vaccine clinical trials are underway.

One vaccine prototype being tested will use a broadly neutralising antibody made in a laboratory. But while the prototype has worked in tests on monkeys, it may still not be practical. The vaccine is expensive, works only for a few weeks or months, and doesn’t appear to be effective against the strain of HIV prevalent in Southern Africa.

In light of this, it does not take a medical expert to figure out that the chances of broad success here are slim. Yet, expensive clinical trials are underway for this prototype in North America, South America, Europe and Africa.

Instead of ploughing more of our limited resources into large-scale vaccine clinical trials, the global community should provide more support to proven strategies for HIV prevention, such as ‘pre-exposure prophylaxis’ or PrEP, where individuals at high risk of contracting HIV take antiretroviral medication to prevent infection.

While there are valid concerns over the possible side effects of long-term ARV use as PrEP, the drugs are getting better and there are now long-term formulas which can be administered just once every month or two. This significantly reduces the discomfort associated with taking daily doses of the drugs while making it easier to for programs to administer.

Where I work, in South Africa, just over 50 percent of the HIV-infected people who could benefit from ARVs are accessing them due to lack funds – leading to over a 100,000 unnecessary deaths for the untreated. The same is true in many eastern and southern African countries – the region worst affected by the HIV epidemic – where nearly half of infected people do not have access to treatment (http://www.unaids.org/sites/default/files/media_asset/Global_AIDS_update...). An HIV-positive person being treated with ARVs is also less likely to pass along the virus, making ARVs a critical tool in preventing the spread of HIV.

This is not to say that all HIV vaccine research should stop -  an effective vaccine would undoubtedly be the most effective weapon against HIV. History also teaches us that in drug and vaccine development, we must experience failures before success. However, research must be appropriately targeted to solutions that are the most likely to work and are easily widely applicable.  

Based on the current reality, HIV treatment and prevention strategies that have been proven to work would be a much better use of the tens of millions of dollars being spent on the large scale vaccine clinical trials. It may not make vaccine researchers happy, but it would save lives on the ground.