Interview: Co-Chair Mitchell Warren

You have described this as a golden age in HIV prevention. What makes you excited about this moment in the HIV response? 

When you look back on the 40 year trajectory of the HIV pandemic, I’m amazed at the momentum that HIV prevention research has had throughout 2020, even in the midst of COVID-19. The year started with very disappointing news from HVTN 702 showing that that vaccine didnt work. But since then, we’ve had the initial results from longacting Cabotegravir (CABLA) showing terrific benefit, at least in a couple of populations. And shortly thereafter the positive opinion on the dapivirine vaginal ring, which is both a woman initiated method and the first regulatory opinion on a long acting prevention tool. We have the Mosaico vaccine trial, the largest phase three trial in years, underway in multiple countries. Very soon we will have results from the AMP studies of antibody-mediated prevention. And we are generating entirely new insights, even from the disappointing results of 702, into what we do need to do for vaccines. In all, we have more safe and effective prevention options available and in development than ever before.  

I’ve never seen so much momentum around so many different prevention modalities.  

What we do with all of those data, though, presents some hugely important unanswered questions.  

 

What are some of those challenges ahead? 

Like any good study, every one of the trial results in the last seven month answers a question and raises a host of new ones. For example, what is the best approach to an HIV vaccine? It clearly wasn’t ALVAC in the 702 trial. But understanding what those results mean and the implications for the next generation of trials is crucial. The AMP results will open new questions, about which antibodies and what antibody responses are most important, and whether we can get that response in a vaccine. 

When you look further downstream, we have this positive opinion on the dapivirine ring. But how do we make a moderately effective, women controlled method available as an additional choice? How do we translate even the partial efficacy seen in trials into public health impact? How do we deliver a vaginal ring in eastern and southern Africa, where vaginal rings have never been available? 

We know that cabotegravir injected every two months is safe and effective for men who have sex with men, and transgender women. We don’t know if it works in cisgender women, and we’re waiting for HPTN 084 to tell us that. Similarly, late last year we got approval of F-TAF for oral prep for some, but not all people, because the trial was never done in cisgender women. So there are huge question marks about how these products might work differently for different people. 

For me, one of the biggest challenges is how we can remove the siloes around these different products and get to a new way of talking about prevention. I think a lot about the difference between options and choices. Seemingly every month or so presents the prospect of new prevention options, with rings, new oral formulations, an injectable. But those only become choices if we act as a global community to set up the policies, programs and funding mechanisms to make those true choices for individuals.  

That’s why HIVR4P is so important. We really are a conference that works to bridge the gaps between developing new prevention options and understanding how we make those viable choices for the individual. And that’s the work we need to accelerate. 

 

Has COVID-19 changed your perspective on how the HIV prevention field should move forward? 

COVID-19 has influenced everything we do. I don’t think anyone in global health, in HIV or infectious diseases, isn’t also working on COVID-19 now.  

Two things really jump out for me. One, how do we make sure that even as we rightly pivot to focus on COVID-19, we don’t lose the amazing gains made in HIV, toward the 909090 targets, in the development of new technologies and prevention options? A couple years ago, we started talking about the tipping point in HIVthat if we could get to the point of having fewer new infections than people dying of AIDS, we would tip toward ending the epidemic. One can also tip back, however. And COVID-19 presents this huge challenge of how do we not only respond to COVID-19 with science, with evidence, with HIV lessons in our head, but how do we make sure that we don’t lose sight of the gains made in the HIV response, in TB and in related global health issues? 

We’ve got to figure out what this new global health architecture looks like for funders, for policymakers, for science and researchers. How do we do respond to the newest pandemic without losing sight of the essential importance of a focus on decadesold pandemics? 

 

We’re entering an era of virtual scientific conferences. What are the major opportunities and challenges for HIVR4P // Virtual? 

For all the work we all do in putting together robust invited speaker sessions, or really remarkable abstract sessions, perhaps the best part of HIVR4P is what happens outside the session room. The kind of dynamism that happens in the hallway, when people are sharing enthusiasm for what they just heard, or new insights or ideas that spark a whole new collaboration.  

I am very confident that we can deliver a great scientific program, because there is great science in HIVR4P. We’ve also got to figure out how to enable more human interaction in virtual settings. Sparking new ideas and new collaborations has always been an important part of HIVR4P. How you get advocates and researchers asking each other questions about their experiences and perspectives.  

One of our biggest opportunities is that, while each of those previous HIVR4P conferences could only bring together 1200 to 1400 people, we have an opportunity to make HIVR4P // Virtual a global conversation that engages thousands of people in real time.  

That’s a great opportunityto be able to look back at HIVR4P // Virtual and say that the conference fed conversations around the world. That’s going to come down to all of us using not just the conference platform but also text messages, WhatsApp groups, emails and chat features. We need to make sure that everyone is talking and taking HIV prevention to a new level.  

 

What are you most excited about learning at the conference? 

I’m most excited about understanding what we do with everything we’ve learned in the last few months, and what we’ll learn in the months ahead. We have all of these study results…what will we do as a global community to make those come alive? How do we make the AMP result relevant to vaccine developers and other antibody researchers? How do we make the cabotegravir result matter for women and men around the world? HIVR4P // Virtual can be a milestone in translating the most exciting, most diverse prevention science into the most exciting and diverse prevention programs of the future. That’s my top question for this meeting…how do we turn those options into choices, and how do we make those choices real? 

HIVR4P: A Unique Opportunity to Advance HIV Prevention by Adeeba Kamarulzaman, IAS president

We are in the midst of a golden age in HIV prevention research. As planning enters high gear for the IAS – the International AIDS Society – 2021 HIV Research for Prevention Conference (HIVR4P // Virtual), I’ve been reflecting on some enormous prevention advances reported over the past year and some significant challenges ahead. Both will take centre stage at the biennial HIVR4P conference, the only global meeting focused exclusively on HIV prevention science 

This next edition of HIVR4P, to be held virtually on 2728 January and 34 February 2021, could not be better timed. It comes on the heels of multiple prevention advances reported at the 23rd International AIDS Conference (AIDS 2020: Virtual)  

At AIDS 2020: Virtual, delegates got the first look at data showing that long-acting injectable pre-exposure prophylaxis (PrEP) is more effective than a daily pill in men who have sex with men and transgender women. Also presented, among many others, was: evidence that improving access to PrEP reduced infections by three-quarters among men and women at high risk in Kenya and Uganda and led to significant drops in infections for women in Cape Town, South Africa; new research supporting harm reduction to reduce HIV in Ukraine and Tanzania; and evidence of dramatic declines in vertical HIV transmission in India, among many others 

The past year also brought the positive European Medicines Agency opinion on the dapivirine vaginal ring and the launch of the Mosaico HIV vaccine study, among many other advances in prevention. Results of the first Phase III studies of antibody-mediated prevention, a potential new prevention tool, are expected later in 2020 and should be one of many focal points of HIVR4P // Virtual. 

HIVR4P // Virtual also takes place at a time of enormous challenges for prevention. HIV research is advancing the search for COVID-19 treatments and vaccines, but COVID-19 is delaying major HIV prevention studies and slowing access to prevention, treatment and care for HIV and many related conditions. And we still face multiple obstacles that predate COVID-19 

HIV remains stubbornly entrenched in many global regions and is even growing in many places among young people, drug users, men who have sex with men, sex workers and incarcerated people. HIV stigma, along with regressive laws and policies, continues to limit access to prevention, including testing. We still need to bridge enormous gaps between the promise of HIV research and the realities of access for millions of people in need worldwide. We also need to expand funding and political leadership to reach the full global potential of the HIV prevention tools we have worked so hard to develop.   

HIVR4P // Virtual presents a unique opportunity to develop collaborative responses to these challenges. In addition to being the only global research meeting focused exclusively on prevention science, the conference is also noted for its commitment to collaboration and inclusivity. The researchers, advocates, funders and policy makers attending HIVR4P // Virtual represent every global region and every field of prevention science. That broad participation, along with the leadership of the IAS, uniquely positions the conference to help translate scientific advances into effective health policy.   

I can also share that alongside HIVR4P // Virtual, the IAS will host the virtual COVID-19 Conference: Prevention examining COVID-19 related prevention advances. We will announce more on that separately this month, October 2020. 

HIVR4P // Virtual and the IAS COVID-19 Conference: Prevention will be the first International AIDS Society conferences to be held since I assumed the presidency of the IAS. I could not be more excited, both about the opportunities that lie ahead to make real and lasting progress against this epidemic, and by the prospect of bringing together the most dynamic leaders in HIV and COVID-19 prevention research, implementation and advocacy. We have our work cut out for us. I hope to see you there! 

OConnor HIVR4P

Interview: Co-Chair David O’Connor

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.