David O’Connor, PhD, is a Medical Foundation Professor of Pathology and Laboratory Medicine at the University of Wisconsin-Madison and chair of the Global Infectious Diseases Division of the Wisconsin National Primate Research Center. David studies the interplay of genomics, immune responses and HIV, and has a passion for improving real-time data sharing to accelerate research. We asked David about HIV prevention challenges and opportunities, and how this unique moment in public health can be leveraged to improve the global HIV response.
As a leading vaccine researcher, what do you see as the biggest challenges and unanswered questions in the search for a vaccine?
One of the biggest questions is where vaccines will fit in an increasingly crowded HIV prevention agenda, where we now have multiple outstanding prevention options. Oral PrEP has provided new options. Long-acting Cabotegravir will provide others. Making a vaccine that offers compelling advantages over these is a challenge we should welcome. But it does raise the bar for how a vaccine needs to perform.
The recent data from HVTN 702, which wasn’t able to replicate the promising findings from the Thai vaccine trial, suggest that we still have a lot to learn.
You research the way HIV evolves to counter immune responses. What does the complex interplay between the virus and the human immune system tell you about the prospects for developing an effective vaccine?
There are different, clever approaches to address sequence diversity — whether it’s mosaic immunizations, or targeting conserved regions of the virus that have a difficult time changing – but it remains a major obstacle.
One exciting step was the advent of inexpensive, high throughput viral sequencing technologies that help us understand the global virus landscape. With more sequence data from more places, and understanding how the virus evolves and behaves within different communities and populations, we can leverage that information for better vaccine approaches for certain populations.
You were involved early in research responses to Zika and your work on coronavirus began in January when few saw the global threat. How has your HIV work prepared you for other emerging infectious diseases?
By the time I started working in HIV, around 1997, history books had already been written about the early years of HIV, and the fierce competitiveness around research responses, which can drive productivity and advance science, but also prevent collaboration and information sharing.
When we had one of the first Zika virus animal model, we took the unorthodox step of making all of our data public in real time, so that others could benefit from our successes and our mistakes. That engendered a lot of goodwill. When we started thinking about the novel coronavirus, we were able to marshal a large team of investigators to think collaboratively.
It’s easier to share information now than in the early days of the AIDS epidemic, in part because of a change in culture and science, where openness and transparency is increasingly the norm. The global scientific community benefitted from getting data out as quickly as possible, to the widest possible audience.
Now, people have been willing to share their results in preprint servers before the manuscripts are formally published. There has been some hand-wringing about short-circuiting the peer review process, but at the end of the day a huge amount of good comes from having this information available so that researchers can learn from it, design better experiments and advance as quickly as possible.
Do you see the HIV research experience influencing the COVID-19 response?
Yes. If we are lucky enough to get a coronavirus vaccine quickly, that work is a direct descendant of investment in adenoviruses vectors, RNA vaccines and other types of vaccine platforms for preventing HIV. They might not have all worked against HIV, but that allowed the quick response to the coronavirus.
Some central concepts of harm reduction and risk disinhibition that we talk about in HIV are also applicable to the coronavirus. The idea of wearing masks as a form of harm reduction makes a lot of sense if you’ve been thinking about condoms as harm reduction for 40 years.
There are important lessons in messaging strategies, too. Prevention messages are going to carry a lot more weight when they come from peers…whether those peers are university students or senior citizens or people living in various communities. As we’re learning how to market PrEP and other HIV prevention modalities, we need to market coronavirus prevention as well. For example, a blue surgical mask may not be as well received as a decorative, fashionable mask.
Just a few months into this new pandemic, we’re already seeing “coronavirus fatigue.” It really underscores how hard HIV advocates have worked to maintain a continuity of messaging and keep the issue as central as possible over a period of decades. We have a lot to learn from people who have been doing this critical messaging work and be careful not to fall into “normalizing” thousands of hospitalizations or deaths just because we get tired of thinking about it.
The messaging also needs to be aware of the realities of peoples’ lived experience. After the 2000 IAS meeting, I was surprised to learn that many people I visited in some of the local communities around Durban weren’t worried about HIV. I couldn’t understand why, until someone explained it to me: When you’re not sure where food or clean water is going to come from, the idea of a disease that could kill you in 10 years just doesn’t register on what you worry about today.
People’s coronavirus risk profiles are going to look different, depending on where they are in life, job and family stability and situation. Understanding that prevention messages need to be tailored to a community’s lived reality is an important lesson learned from HIV.
How can what we’re learning from COVID-19 translate into HIV research or practice?
The importance of data sharing is one key lesson. When Zika emerged, I started giving talks where I pointed out how few HIV papers were in preprint servers. People said that they needed to put their Zika data in preprint servers because it was a public health emergency. But what about HIV? We weren’t sharing data, and that needed to change. Now, I think the rapid data sharing we’re seeing in the coronavirus response is going to be a new norm. And we’ll be able to apply those lessons back to HIV.
What kind of research advances do you hope to see among the COVID-19 studies presented at HIVR4P?
By January, we should have a handle on vaccines specs, data from several types of vaccines from different platforms, many of which started in HIV and begin to get three to six months data on the durability of vaccine responses. I’d hope to see data on vaccine performance, potential adverse events and potential comparative immunogenicity.
What else are you looking forward to in the conference program?
We are really at a critical time in prevention. We will have the results from the first antibody trials, more insight into what happened in the HVTN 702 vaccine trial and new data on long-acting antiretrovirals for prevention…just to mention a few key areas.
Figuring out where to go as a field is an exhilarating and invigorating part of these meetings. HIVR4P is an opportunity to take a deep breath, contextualize findings and decide what the next five years of HIV prevention should look like.