Ravindra Gupta had studied drug-resistant HIV for more than a decade when he first encountered Adam Castillejo, who would become known as the “London patient,” the second person in the world to be cured of HIV. Gupta, who goes by Ravi, was a professor at University College London straddling the clinical and academic worlds when Castillejo presented as both HIV-positive and with relapsed lymphoma, after a previous transplant using healthy stem cells from Castillejo’s own body had failed.
Building on work by German hematologist Gero Hütter and others that went into curing the first person of HIV — Timothy Ray Brown, known as the “Berlin patient” — Gupta and his colleagues proposed using stem cells from a donor with a rare genetic mutation that prevents certain individuals from being infected with HIV. Castillejo agreed and had his transplant in 2016. Seventeen months later, Gupta and his team took Castillejo off the antiretroviral drugs that kept his HIV at bay. In 2019, three years after the transplant, Gupta published the results in Nature, confirming Castillejo was cured of HIV.
The news shook the scientific world and revitalized the search for a cure. Gupta was hired as a professor of clinical microbiology at Cambridge and established Gupta Lab on the school’s biomedical campus to continue his research.
A few months later, the coronavirus pandemic hit — and with nations going into lockdown and medical systems taxed to their breaking point, he found himself drawn into the response.
“Respiratory viruses were never anything I would consider getting into. I didn’t think we had the skills or expertise to be useful,” Gupta said recently. But, he added, “the clinical interface of what I do dragged me into working on SARS. Things got bad here in March, and everything shut down. One of the desperate needs was identified as rapid testing.”
Soon his team had completely pivoted and was publishing some of the first research validating rapid and antibody tests for the coronavirus using techniques honed during HIV research. Over the past 2 1/2 years, Gupta Lab has cranked out cutting-edge research, describing how new variants arise and providing some of the first evidence that breakthrough COVID infections were possible in vaccinated individuals.
At his lab at Cambridge, he discussed both the remarkable strides made by scientists over the past three years, as well as the consequences of the public’s diminishing trust in scientific knowledge.
This interview has been condensed and edited.
Q:</b> How has earlier research on AIDS/HIV affected the response to the coronavirus?
A: The response to SARS-CoV-2 has accelerated largely because of HIV advances. There have been huge advances in how we make drugs, target viruses, and a lot of this technology has been honed on HIV.
Q:</b> What are the similarities between these two pandemics?
A: Both have created a huge panic, SARS-CoV-2 more than HIV — for good reason, because it is respiratory. Certain people are more vulnerable than others, and socioeconomics certainly matters. Also, in this age of availability of vaccines, the rich versus poor, global north versus global south — all of those inequalities have been coming through.
Q:</b> Has this global emergency improved your ability to work with your colleagues across various disciplines?
A: It’s certainly galvanized a load of interactions we otherwise wouldn’t have done. We got interested in immunology, we did some very cutting-edge work with colleagues downstairs and in different parts of the building. We started using stem cells to make artificial lungs to do experiments in. All of these things started happening as a result of the emergency. People who we would have never talked to, ideas we would have never had. So it’s really been exciting scientifically.
Q:</b> Does fatigue account for the public’s waning response to COVID?
A: Yeah, I think so. I think the intensity has caused a burnout of emotional energy. Of course strides have been made in HIV over about 20 years. That happened very quickly for COVID. And in the absence of a vaccine and mRNA technology, we would be in a much darker place.
Q:</b> Across society we are seeing a decline in trust in institutions, but in your field there are rather severe consequences to people refusing to get a vaccine, for example. Has that affected the way you think scientists and the medical establishment must communicate with the public?
A: I think there’s a general lack of trust between the public and people who provide information. That’s partly driven by sectors of the public spreading misinformation. I think the actual communication was quite good in the beginning — you got clear messages and I think it was quite good. Public health messaging has gotten more complex because no one wants to wear masks.
For example, after vaccination, people thought we’d be mask-free. We published a paper in Nature on breakthrough infections and the CDC the next week cited our work as a reason to mask, even with the vaccine. Which sounds normal now, but back then it drove people crazy. But it was the right thing because your responses after a few months could wane, and plenty of people with double-dose vaccinations can end up with reinfections the second time around. So that all contributed to confusion based on lack of education or knowledge of nuance. And one thing we have to deal with now is that communication takes nuance that even scientists can’t grasp. So expecting the public to grasp this is pretty much impossible. So we’re at a crossroads for how we communicate complex messages.
Q:</b> Are there long-term implications if we can’t persuade a larger proportion of the population to be vaccinated?
A: Circulation may take off in places like China, where the population has been relatively naïve when it comes to vaccines, and the vaccines aren’t necessarily the best ones. And if people don’t get their boosters on time, we may end up reaching a period when it becomes another major health problem of the magnitude we have already seen. I can foresee in a few years’ time we may be in trouble again. The worrying thing is that we are winding down a lot of things we developed to deal with this.
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