African-led discovery and innovation

In his keynote address, Professor Salim Abdool Karim described how a discovery made in Africa has led to a possible intervention for use in Africa – and discussed what it will it take for this to be the norm rather than the exception.

In the past two decades, much progress has been made in enhancing access to antiretroviral therapy. But suggested Professor Salim Abdool Karim, Centre for the AIDS Programme of Research in South Africa (CAPRISA), in his keynote address on Wednesday morning, this progress has not been matched in HIV prevention.

Furthermore, there is an enormous gender effect: “In Africa, adolescent girls and young women bear the brunt of the HIV pandemic,” Salim pointed out, “so much so that, when you take young boys and girls below the age of 24, we see almost a fourfold difference in several hyperendemic communities.” In one study, HIV prevalence in increased from 1% to 1.8% in males of different age groups but from 2.6% to 24.7% of females in the same age groups.

Salim went to explain that these disappointing findings were not from the want of trying. Many different strategies were developed and tested: “And we failed. We failed so many times that we were often referred to as the experts in failure.”

Yet he and his team persisted, eventually making the landmark discovery that tenofovir gel could block HIV infection: “That provided us with proof of concept that an antiretroviral can prevent sexual transmission of HIV.”

Pre-exposure prophylaxis (PrEP) has been shown to be highly effective and is now the standard of care in HIV prevention. Yet, in the real world, its impact has been less than hoped. The reason, suggested Prof. Karim, is at least partly due to the demands PrEP makes on young people. “We are asking them to take a tablet every day. It’s really a challenge. Those who do start treatment, a third of them stop taking the drugs within three months. And by the end of the first year, we’ve lost two-thirds of them. So we’ve got to do better.”

In search of long-lasting PrEP

Salim therefor set his sights on a new goal – long-lasting PrEP, delivered through an injection every six months. A possible option was suggested when US researchers identified ‘broadly neutralising antibodies’ – antibodies produced by a small number of individuals that are able to neutralise a wide range of HIV strains.

“We screened thousands of our patients, to see if any of them developed this broadly neutralising antibody,” said Prof. Karim. In patient 256, a women enrolled in a study in 2014, they hit the jackpot. Serum from this patient had remarkable properties: “We took the serum, and we tested it against 400 viruses from throughout the world. And what we found is that the antibodies killed four out of every five viruses. We were astounded.”

Thanks to collaborations with US teams, his group was able to isolate the B cell making this particular antibody and were able to show that it completely protected non-human primates from infection. “To this day, we’ve not been able to infect a monkey that has received even low doses of the CAPRISA256 antibody.”

Prof. Karim then partnered with the US National Institutes of Health (NIH) to manufacture the antibody therapy, while EDCTP2 provided funding for its clinical evaluation. The South African government has also provided financial support. Safety has been demonstrated and the first efficacy data are eagerly awaited.

Lessons to be learned

Prof. Karim also discussed the multiple contributions made to SARS-CoV-2 characterisation in South Africa during the COVID-19 pandemic, work of huge global significance. He also emphasised the importance of ensuring that African-based researchers are integral to high-level global health conversations.

Indeed, one of his take-home messages was of the importance of being part of global networks and partnerships: “Excellence is never done alone,” he suggested. “Excellence is about global partnerships. It’s about collaborations.” By way of illustration, he suggested that the broadly neutralising antibody work has involved almost 200 different collaborators across all continents. “That’s how science is done. And it’s led by scientists in Africa.”

Sustaining this excellence, he argued, is dependent on capacity building: “The way we sustain it is by training and treasuring the next generation – creating the opportunities, enabling them to rise to even greater heights.” This requires funding, and Salim also made a forceful plea for more funding from government in Africa: “It’s our job to advocate our own governments to put more money into science.”

He concluded by quoting the wisdom of Plato: “Excellence is not a gift but a skill that takes practice. You have to do it over and over and over till you get it right.” And EDCTP funding, he suggested, was a critical way in which these skills can be built.

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