More than 30 years after the emergence of effective treatment, HIV/AIDS is largely considered a chronic and manageable disease in high-income countries like the U.S., where people with regular access to antiretroviral therapies (ART) are living full and healthy lives. Yet, while the public may have grown tired of rock stars and philanthropists talking about its impact, the fact remains: AIDS continues to be a leading cause of death in Africa and other resource-constrained parts of the world.
The HIV Frontiers Program at the Bill & Melinda Gates Foundation is poised to change that trajectory, incentivizing and driving cutting-edge science to create long-lasting and affordable ways to make this disease go away.
In our 2022 Impact Report, we profiled the man behind this bold initiative, Dr. Mike McCune, a renowned immunologist who began his medical career over four decades ago, treating people infected with HIV at San Francisco General Hospital when HIV/AIDS first exploded onto the scene. Jenn Alcorn, head of Gates Philanthropy Partners, recently caught up with Mike to understand his work.
Mike, can you share what the Frontiers program is doing? I’m not a scientist so tell me in a way I can explain to my mom.
We are working to develop a single-shot cure for HIV that is not only safe, durable, and effective, but also accessible, affordable, and acceptable for all of those in need, wherever they may live. We imagine this to be a therapy – benefiting people who are infected – that would suppress HIV in the absence of daily ART, enhance their health and the quality of their lives, prevent them from transmitting the virus to those around them, and – importantly – also prevent them from becoming infected should they be exposed to HIV in the future. Ultimately, of course, we aim for an intervention such as this to end the HIV pandemic, once and for all.
A lot of your work focuses on gene therapy for sickle cell disease, why is that?
HIV and sickle cell disease are both diseases that affect the blood stem cell, the mother cell of the blood system, and/or the circulating blood cells produced by it. We know from recent studies that ex vivo (outside the body) gene editing of the blood stem cell can result in the generation of normal red blood cells, thereby preventing the scourges of sickle cell disease. Since this approach is complicated and resource-laden, we wanted to find a way to target the blood stem cell inside the body (in vivo) with a “single shot” that could be delivered as an outpatient and result in a similar outcome for those with sickle cell disease. Once we cross that hurdle, we reasoned that the same technology could be applied to modify blood stem cells in a way that would lead to a “cure” for HIV.
Of course, and at the same time, we will have cured a painful and deadly disease that is prevalent in sub-Saharan Africa, killing 90% of the children born with it by the age of five. In the U.S., sickle cell disease primarily affects people of color and receives low funding levels compared to diseases common in people of European ancestry, and a simple, effective, and affordable intervention would have enormous clinical impact.
We all lived through COVID-19 and the incredible pace of vaccine development. Will the advent of mRNA technology make a difference in your work?
Yes, for sure: the technology underlying mRNA vaccines for COVID-19 can be applied to HIV. By example, another approach that we are taking for the development of a “single shot” cure for HIV is to develop a therapeutic vaccine for HIV that would activate the immune system to suppress HIV when the HIV-infected individual is not on antiretrovirals. As a matter of fact, the Gates Foundation funded the company, BioNTech, to work on mRNA vaccines of this type for malaria and tuberculosis in 2019, prior to the COVID-19 outbreak, and researchers there quickly pivoted to apply their knowledge to urgently developing a vaccine against COVID-19.
Are we really talking about a cure?
As a scientist, I’m trained to be both precise and cautious, which is why I like to put quotation marks when I talk about a “cure” for HIV. At the bottom line, we hope to develop an intervention that will lead to durable suppression of the virus in the absence of daily ART. Rather than to prove that every single virus in the person has been eradicated, we wish to keep any virus present under control. In much the same way as cancer treatment is judged in terms of “years of cancer-free survival,” this might be most properly viewed as a “remission” or a “functional cure” of HIV disease.
What’s the role of philanthropy and donors in your work?
We are pursuing high-risk research that will take time, resources, and the contributions of multiple partners. While many researchers wish to bring curative interventions for HIV and sickle cell disease to the poorest of the poor around the world, the usual funding sources supporting their work have misaligned incentives. Thus, reaching a goal as aspirational a “single shot” cure for HIV is not usually the provenance of academic institutions funded by government sources. It is also not the mission of companies beholden to shareholders looking for short-term profits. We wish to motivate researchers around the world to take the risk to tackle this problem, to form teams with diverse strengths that are more likely to succeed, and to reach for the stars. In such a setting, philanthropy is essential: it can serve to provide the right incentives, both in terms of resources and, as importantly, in maintaining the focus on a long-term vision for a better world. That’s why the HIV & Sickle Cell Disease Fund recently launched by Gates Philanthropy Partners is so exciting: finding and delivering a cure for HIV around the world will only be possible if we are able to partner with others who share that vision - and I hope that many can join us.
Are you optimistic we can get this done?
Absolutely. After five years of pursuing a variety of paths, we have landed on two extremely promising approaches for a “single-shot” cure of HIV disease: therapeutic vaccination and in vivo gene therapy, the latter of which can also be applied to a cure for sickle cell disease. We understand the basic science, we are seeing encouraging data, and we now need to carefully work through all the rigorous steps to bring new treatment to the clinic for proof of their effectiveness and safety. Given the pace of the work now, I’m confident that we will one day see a world that can control and eventually end the suffering caused by both of these horrible diseases.
What will it mean for the world when a “single-shot” cure is ready?
A “single-shot” cure will save the lives of millions of people around the world who do not have access to antiretrovirals or to treatment for sickle cell disease. Without the need for daily medication, which is expensive and difficult to adhere to, the lives of millions of others will improve dramatically. I’m confident that we will one day see this world. Once we have these technologies in hand, I am also confident that they will be applied to multiple other diseases for which effective and accessible interventions are not now available.
Though this world is not yet a reality, it is visible on the horizon. Now is the time to reach for it!