An Interview with Françoise Barré-Sinoussi
The Nobel laureate, former president of the International AIDS Society, and passionate advocate for HIV prevention, treatment, and cure research recently retired. But she is far from finished with her life’s work.
By Kristen Jill Kresge
Françoise Barré-Sinoussi needs no introduction. There are a handful of individuals who have been involved in the HIV/AIDS pandemic since the very beginning and Barré-Sinoussi is one of them.
In 1981 when the US Centers for Disease Control and Prevention published the first repor
ts of a deadly new illness that would eventually become known as AIDS, the causative agent was unknown. At the time, Barré-Sinoussi was working as a retrovirologist with her mentor Luc Montagnier at the Institut Pasteur in Paris, a non-profit research institute that she joined in the early 1970s even before earning her PhD in 1975. It was at the Institute Pasteur that she joined scientists who were trying to determine the cause of this mysterious new disease.
The rest, as they say, is history. In 1983, she and Montagnier identified a new retrovirus as the cause of AIDS. As Barré-Sinoussi recounts, this was the first time in her scientific career that experiments she and her colleagues conducted verified their hypothesis. In 2008, she and Montagnier were awarded the Nobel Prize in Physiology or Medicine for their role in discovering HIV. Not bad for your first proven hypothesis.
Since then Barré-Sinoussi’s career has been shaped by the pandemic. She is a vocal advocate for HIV prevention and treatment. Most notably of late she has been a leading voice in the push for HIV cure research. Always a realist, Barré-Sinoussi recognizes that a traditional, sterilizing cure may be a long shot because of the virus’s uncanny ability to form reservoirs in various cells and tissues within the body. However, the possibility of achieving a sustained remission for HIV-infected individuals is something Barré-Sinoussi sees as an achievable goal. Her efforts were integral in establishing an agenda for cure research and she is a mainstay at annual meetings to address the latest findings in cure-related work. Barré-Sinoussi also served as president of the International AIDS Society (IAS) from 2012 to 2014.
At the end of August, Barré-Sinoussi, at age 68, retired from active research, which she notes was a requirement not a choice. Barré-Sinoussi has a ready and hearty laugh and remains humble despite her vast achievements. She is steadfast and passionate, a quality she thinks all scientists must possess to be successful. Otherwise, “it’s just a job.” Although she may be retired now, her calendar of engagements suggests otherwise, and she seems far from finished with her work.
Barré-Sinoussi spoke recently with Managing Editor Kristen Jill Kresge about her remarkable career, what it was like to be a woman HIV researcher in the early days, and her views on the state of vaccine and cure research today.
Your involvement with HIV started with the discovery of the virus. When you reflect on that, what was it like at that time?
The discovery of the virus was of course very exciting. As a scientist it was really wonderful because we were making a hypothesis and defining approaches to try to confirm this hypothesis. For me it was really the first time in my life that we were making an experiment to verify a hypothesis and the hypothesis was confirmed. So as a scientist it was really exciting. But as a human being, it was really awful. At that time, AIDS was really a tragedy. People were dying. They were young, dying of this new disease, and knowing as a scientist that it would probably take time, too much time for many of them to benefit from any treatment that science could deliver was really very, very stressful.
How has your thinking about the virus changed since the earliest days? Did you initially think that the road to treating, preventing, or even curing HIV infection would be easier than it turned out to be?
We were very naive in the early 1980s. After the discovery of the virus and the linking of the virus and the disease we thought that it could be very easy and very fast to develop treatment or even to develop a vaccine. We started to understand a little bit later on the complexity of the interaction between the virus and the different tissues and compartments in the body. Then we moved from a naive vision to a much more complex vision, which is the reality.
However, I think there was some rapid progress. First, in terms of development of diagnostic tests, which was a very important step. This quickly made it possible to prevent transmission of the virus by blood and blood derivatives. Secondly, AZT was introduced in 1985, so it was quite rapidly that the first inhibitor of reverse transcriptase was in clinics. Of course it was not sufficient and we had to wait until 1996 to see the first results of combination antiretroviral treatment, but I would say progress has been quite fast in terms of treatment. If we think about prevention, we still do not have a vaccine today; however, we have learned a lot over the years. We have also learned progressively that treatment is prevention.
What role did activism play in accelerating HIV treatment?
The role of activists has been really critical. The pressure they put on pharmaceutical companies, on governments, and on the decision makers has been really critical for making progress in the access to care and treatment. That was the first time I’ve seen such a movement to get the people affected by the disease access to what the scientists were delivering. This is a good lesson for other fields. I think we really need the same movement today for curing people that are infected with HIV.
You’ve recently been one of the main scientists pushing the cure research agenda forward. Do you consider yourself an activist?
Some people say that. It’s difficult for me to know whether or not I am an activist. What I know for sure is that for me, it’s unacceptable as a scientist to not be part of any movement for improving science and improving the delivery of tools for the benefit of people that are affected by a disease like HIV. Scientists have a role. It’s their responsibility to apply pressure if the tools they develop cannot be accessed by the people who are affected by disease.
What do you think the prospects are today for the development of a preventive HIV vaccine?
Today I think we are going in the right direction. I would not have said that before the data of the Thai trial, RV144. But since 2010 there’s been wonderful progress in terms of the data with the new broadly neutralizing antibodies and exciting data that suggest non-neutralizing antibodies may also be important for ADCC [antibody-dependent cellular cytotoxicity] activity. We also need to understand better the T-cell response that might be important for vaccines to induce. So I think it’s really progressing in the right direction and the reason for that, in my opinion, is really because scientists are combining basic science together with pre-clinical and clinical research. We are really starting to see the results of that so I’m very positive today. I would not have been so positive before 2009.
It’s good we are doing the interview now then.
(Laughs.)
What are your thoughts on the prospects for therapeutic vaccines?
Therapeutic vaccines are a critical issue for cure research. I cannot separate the two because probably therapeutic vaccines will be one of the components of a future cure strategy. There are several promising approaches today. The wonderful data from Louis Picker using the CMV [cytomegalovirus] vector are really encouraging. There are also data using chimeric antigen receptors in order to improve T-cell responses and some other approaches based on immune therapy for cancer, which are also encouraging. I think we should go in both directions—preventive vaccines and therapeutic vaccines together.
Do you think HIV vaccine research is fueling scientific discovery in other fields, such as cancer research or even more recently with Ebola? And in the case of Ebola has the experience working with HIV/AIDS on the ground influenced the response to this latest outbreak?
I would say for cancer research today the opposite is really happening. It’s really the data regarding immunotherapy in cancers that is driving new avenues for HIV cure science or HIV vaccine research, in my opinion, which is good. However, HIV research all together has certainly impacted other areas. With HCV [hepatitis C virus] treatment for example, the approach was based on the development of HIV antiretroviral treatment.
This is the reason I would like to push for more interaction between HIV and non-HIV researchers. This is the way to go if we want to have new creative ideas that can be useful for both HIV vaccine and cure research and other diseases.
You also mention Ebola. I remember when the Ebola outbreak was announced and the information we were getting at the time reminded me very much of the early years of HIV. Of course it is not the same virus and the disease outcome is not the same, but the reaction of the population in Africa really reminded me of what happened with HIV. They were afraid about contamination, the behavior of the police, and the behavior of doctors. We were in a very similar situation with HIV. And certainly the lesson that we learned from HIV is that the communities need to be involved in giving information and counseling to the populations. This is critical in terms of research for Ebola. And I know that some of my colleagues working on HIV stopped working on HIV to start clinical trials on Ebola. Some of my colleagues that were involved in social science studies of HIV/AIDS moved rapidly to start working on Ebola. So I think the lessons learned from HIV/AIDS are very useful for other outbreaks like Ebola. HIV/AIDS can be used somewhat as a model. Not a perfect one, but it is useful.
Considering some of the recent disappointments in cure research, including the famous case of the Mississippi baby who was thought to be cured after very early initiation of therapy but later experienced viral rebound, it seems that the goal of curing HIV may be even more difficult than anyone appreciated. Do you think a true HIV cure is possible?
The view of cure research has changed for people outside the field. For those involved in the field of cure research I don’t think the outlook has really changed because it’s been for years that we are mentioning a sterilizing cure, or a functional cure or sustainable remission, personally a term that I prefer. We knew already that obtaining a sterilizing cure would be what I call on my slides, an impossible mission. Then I cross out impossible mission and put remission—that’s possible. This is not something new. We have learned a lot from the Mississippi baby and the Boston patients. The viral rebound that occurred in these cases is just telling us that we don’t have the right tools to measure the viral reservoir. This is very important. One of the priorities of cure research is really to develop new tools to quantify the reservoir.
Today, according to the technology and knowledge we have, a cure is still very difficult. However, maybe in the coming years we will have new strategies and new biomarkers, for example, to identify cells that carry the virus and we will be able to target those cells in different compartments of the body. We don’t have that today but we cannot say whether in the next 10 years we will have such tools. You never know in science so it’s impossible to say.
However, it’s certainly more realistic to think about sustainable remission. We know that there are patients in the VISCONTI cohort that have been treated very early on—within 10 weeks after infection—and the vast majority of them after more than 10 years are still controlling the virus and are not on treatment anymore. They are what we can call a sustainable remission. So those people already exist.
Still, to achieve a functional cure on a large scale will take time and will certainly require a combination of approaches. We need to have better strategies. We need innovation and creativity. We need a novel generation of scientists. We need to interact better with non-HIV researchers. It’s critical today to have HIV cure researchers interact with scientists working in cancer. We also need to have public-private partnerships. This is very important if we want to accelerate cure research. This is a list of what we need and this could be achievable I’m sure. These are the aims of the IAS HIV cure project.
Does either cure or vaccine research in your opinion need more funding?
If you ask this question of a scientist they will always say ‘of course.’ We always need more money.
But when you work together in a consortium of researchers with different expertise, you spend less money. It’s also one of the ways to not do—I’m sorry to say this—what has been done in the past for vaccine research. To be very empiric and try everything: all the vectors, all the constructs, without knowing where we were going. You spend a lot of money doing this and in the end you could have nothing. In my opinion, if you want to do more with less money, you can, if you are creative and work better with others.
Do you think African nations could play a broader role in HIV research?
I think it’s critical to promote African leadership. This is critical because there is a link between the development of science in countries and economic development. So it’s critical for the populations of those countries and it’s critical for their economies. What I hope will happen in the future is to have more and more consortiums of the African countries working together with African leaders. The CAPRISA [Center for the AIDS Programme of Research in South Africa] program in South Africa is a good model, in my opinion, of strong leadership and training to strengthen the capacity of a new generation of researchers working together in South Africa today.
So what convinced you that it was the right time to retire?
I was obligated to retire. In France when we arrive at a certain age we have to retire. We have no choice. So that’s the reason I had to retire. I do not have a lab anymore but it was time for the people working with me to be totally independent and to have their own laboratories and to develop their own programs. I think it was the right time to do that. That does not mean of course that I am not doing anything anymore. I will continue to advocate for cure research for IAS. I will continue to be a member of different expert panels at an international level. I will continue to coordinate research programs in Southeast Asia, and particularly in Vietnam. So I think I’m going to be very busy as a volunteer.
You are inarguably the most famous woman in HIV research. What was it like being a woman researcher in this field early on?
For sure it was not easy. It was very difficult to be heard by the male researchers. For me there was also the fact that I was much younger then, of course, than I am now. When you are a young woman it is very difficult to get men to listen to you. However, even in the early ’80s a lot of women were involved in HIV research so they really have been at the forefront.
What advice would you give to young women who are just starting out in science?
Science is really a passion. If they don’t see it that way, it is just a job. If they are really motivated to become a scientist, not for themselves, not for their CV, not for making publications, not to be known, but really to do it for others, then it’s the most beautiful work that you can do. When you are able to deliver tools to help those who suffer, this is really great. It is so wonderful to see people that I know still alive and happy to live. My advice is to be very persistent and the results, the success will happen. They have to be ready to overcome all the obstacles, and if they are persistent and motivated they will.
When I talk with women affected by the disease or with drug users, they are expecting so much from science. They believe in us so it’s our duty to try to give our best to respond to their expectations.
If you could go back 30 years in your career, is there anything you would have done differently?
Maybe one thing. One thing I should have done but it’s too late is spend several years working in a resource-limited setting. That’s the only thing. The rest I think I would have done exactly the same. Nothing is perfect—you can always do better for sure. But at the end that’s not so bad.
follow-up of the RV144 trial. “The goal of the P5 partnership has been to translate the RV144 learning to South Africa and test modified vaccine components from RV144 that are based on clade C inserts with the goal of both improving the efficacy that was observed in RV144, and ideally prolonging that protection,” said Nina Russell, deputy director of HIV at BMGF.
at Ebola infection during the latest outbreak—and Kentucky Bioprocessing, which uses tobacco plants to express human monoclonal antibodies, or “plantibodies” (see 
GSK is currently conducting a Phase II trial involving 3,000 adults and 600 children in western Africa, but not in the three countries most affected by the epidemic. ChAd3-ZEBOV was set to be part of a big Phase III trial in Liberia, potentially enrolling 27,000 volunteers, but plans were halted earlier this year as the outbreak ebbed.
But some researchers would like to go much further than this, calling for new ways to stimulate investment in vaccines that do not have a commercial incentive. Stanley Plotkin, an executive advisor to Sanofi Pasteur and researcher who helped discover the rubella vaccine, joined Princeton University molecular biology and infectious disease expert Adel Mahmoud and Jeremy Farrar, director of the UK’s Wellcome Trust, in calling for a $2 billion global vaccine development fund to fill the gaps from market inefficiency and public-sector inability or unwillingness to fund vaccine development for infectious diseases (NEJM 373, 297, 2015).