"We're Not Done"

Chris Beyrer, current President of the International AIDS Society, talks about the remaining challenges to reducing HIV incidence in key populations and continuing the battle against AIDS.

By Kristen Jill Kresge

This July, HIV researchers, advocates, and policymakers will once again gather in the coastal South African city of Durban for an AIDS conference. Sixteen years ago the International AIDS Conference was also held in Durban. Then, people in developing countries, including South Africa, which remains the hardest hit by HIV/AIDS of any country in the world, were dying because they lacked access to the life-saving antiretrovirals that by that time were becoming a mainstay in moChris-Beyrer-Oct-2015st rich countries. In South Africa the situation was particularly troubling because of a history of AIDS denialism. But the conference in 2000 in Durban marked a sea change. It started a “movement,” as Chris Beyrer, current President of the International AIDS Society (IAS) and professor of epidemiology at Johns Hopkins Bloomberg School of Public Health, recalls. “We changed the world and showed that you could treat millions of people with a complex disease in the poorest countries in the world and save lives.”

Since then, access to treatment has increased dramatically. According to the latest data released by the Joint United Nations Programme on HIV/AIDS (UNAIDS) this May, 17 million people worldwide are now receiving antiretroviral therapy. In eastern and southern Africa, the number of people on treatment has doubled since 2010, UNAIDS reports. When the AIDS conference returns to Durban in July, this time for AIDS 2016, it will be taking place in the country with the largest HIV treatment program in the world.

But, as Beyrer attests, the work is far from done. “We’re less than halfway there on treatment and we’re not implementing the prevention [options] we have,” he says. “I think we’ve declared victory too soon. Nobody ever wanted the end of AIDS to be the end of the AIDS response,” he says.

Beyrer lauds the goals set recently by the international community to combat HIV/AIDS but emphasizes that HIV prevention services must be implemented in key populations for these goals to be realized. These ambitious targets include a call to end the AIDS epidemic by 2030, as well as the scourges of malaria and tuberculosis, as part of the Sustainable Development Goals (SDGs) adopted by the United Nations to replace the Millennium Development Goals (MDGs). There is also the 90-90-90 target set by UNAIDS that calls for 90 percent of people living with HIV to know their infection status, 90 percent of all people with HIV to receive antiretroviral treatment, and for 90 percent of all people who receive treatment to achieve a suppressed viral load—all by 2020.

The “movement” that began in Durban 16 years ago faces several other challenges today. There are increasingly constrained budgets for HIV/AIDS programs globally, there are regions of the world that are locked in protracted periods of civil war, there is a devastating international refugee crisis, and there are many places where HIV incidence continues to rise in key populations. In 2015, 2.1 million people were newly infected with HIV, but behind this statistic are multiple disparities, according to the Global AIDS Update by UNAIDS. One of these disparities is that while new infections declined by four percent since 2010 in eastern and southern Africa, the number of new HIV infections in Eastern Europe and Central Asia actually increased by 57 percent over that same period. It is in these places that Beyrer has spent much of his career working with key populations. His focus on HIV/AIDS, epidemiology, and human rights has taken him around the globe. He has done extensive research in Thailand, Burma, China, India, and across Southeast Asia, as well as in Russia and Kazakhstan. He is as highly respected by scientists as he is by HIV and human rights advocates for his work with marginalized populations. Beyrer has served as president of IAS since 2014, a position he will hold until AIDS 2016 closes in Durban on July 22.

Beyrer talked with Managing Editor Kristen Jill Kresge about his two-year term as IAS President, his views on HIV prevention today, and what to expect when AIDS 2016 opens in Durban next month.

The field of HIV prevention has been buoyed recently by promising results, particularly with oral PrEP (pre-exposure prophylaxis). What is your take on the state of HIV prevention today?

The first place to begin is to say that indeed there’s been a huge investment in new preventive technologies and approaches. Certainly oral PrEP, either daily or intermittent, but certainly daily oral PrEP with Truvada has turned out to be the most effective of the new prevention tools. And I’ve been impressed, as I think many have been, that the effectiveness data look even better than the efficacy data. That doesn’t always happen, and it’s really very striking.

But it seems that uptake of PrEP is slower than hoped for. Why do you think that is?

If you had said to me five or eight years ago that we’d have a new prevention technology that if adhered to has effectiveness levels approaching the high 90s or even higher, we would all have thought, I bet, that there would be a sea change. What we’ve seen instead is the US really leading the effort to implement this with FDA [US Food and Drug Administration] approval and CDC [US Centers for Disease Control and Prevention] guidelines, training for providers, and funding. Now in the US there are well over I think 34,000 or 35,000 people at risk of HIV on PrEP. So that’s just incredibly encouraging.

Then we look at the landscape globally and we are looking at what I would say is lax implementation—slow and frustrating. So why is that? I would say first of all, for some of the G8 countries like the UK, there’s no question that the price of Truvada has been a barrier. That isn’t the case in much of the world—it’s an inexpensive generic drug in Thailand, for example, where they’ve approved the use of Truvada. It’s a generic formulation that costs about 30 cents a day or even less, and they have implemented it as part of their national program. So I don’t think cost explains it all. There are certainly regulatory concerns and there’s also been uncertainty, I think, on the part of many governments about where the international donors are. Is PEPFAR [the US President’s Emergency Plan For AIDS Relief] going to support this? Is the Global Fund going to support it? That finally does seem to be happening.

But I think the other issue really gets to the challenge of who needs this. If a country has, for example, programs for youth and is worried about youth at risk, you look at PrEP and you think: we have millions of young people in this country under age 25, are we going to put a generation on PrEP?

But when we look at it from a public health perspective, that’s not what we’re talking about at all. In the US, for example, we have quite a small population of people who account for most of our new infections—63 percent are young gay men. And we’re particularly worried about young gay men and transgender women of color. It is actually a very small population who are very heavily burdened and who could really benefit from this intervention, so the whole cost analysis becomes a very different thing. But it’s very, very difficult still in so many parts of the world for people to do anything meaningful for people who are really at risk. What governments want to do is big, cheap, generic programs for people who are at very little risk.

Obviously a great deal of your work involves identifying and working with those at high risk, often marginalized populations. Should preventive approaches be targeted to these populations and how can that be done?

I think the epidemic is going to force us to do that. First of all, because we’re just not seeing the resources we need. And secondly, because we’ve passed an important milestone in 2015, which is that—this is UNAIDS data—the majority of new infections, over 50 percent, are in key populations worldwide. So this is the undone work of the response and this is where HIV is going to linger. Sadly, we see this in many countries including our own. Rates in heterosexual populations are in decline. Thailand has also achieved dramatic declines in heterosexual transmission and made tremendous accomplishments in preventing mother-to-child transmission, but has a hot epidemic in young gay men. I published on this more than a decade ago, saying these epidemics are going in different directions. And you hate to be proven right by human suffering, but in fact we were right.

I think the other discussion that is really important to have, which now is beginning to happen in some fora, is to be able to say we’re actually talking about a relatively small number of people who really need these interventions. It’s not about commitments to enormous numbers of people, which we all understand there are not the resources for. It’s really about addressing where the epidemic is, and that is in relatively small pockets of very high-risk transmission.

This is still a virus that’s transmitted in a very specific number of ways. People are now all concerned about the fishing communities on Lake Victoria, but this is not something inherent about fishing. This is about sex workers, alcohol, and men with cash. It’s an old story but it’s one where, again, we need to have preventive interventions that fit with people’s actual risks.

That is actually a perfect segue to the ring results, which is an intervention tailor-made for women at high risk of HIV who are unable to use other prevention strategies. What did you think of the recently reported results and the future licensure and implementation of the dapivirine ring?

I think many of us had hoped that there would be higher efficacy, and I think it’s striking that both trials are so close in range of efficacy, that kind of 27 to 31 percent range, which is just right on the edge of making it worth fielding. That makes it challenging. The lack of efficacy for younger women and the clear adherence issues for younger women really is a challenge because they are the people we’re obviously most concerned about in terms of incident infection.

I do think that this starts to move us toward the idea of a menu of options. It is an additional option for women right now who have relatively few. We know that we’re pretty far along in the development and testing of a ring that will also have contraceptives and that would be a wonderful additional option, so we have to herald that.

I don’t know how many settings the ring is really going to be relevant for, but there’s no question that if you look at the epidemiology in East and Southern Africa, we have just been unable to reduce incidence. In the placebo arm of both of those trials, incidence is extraordinarily high—it’s in the 6 percent range, and these are women who are getting counseling and their sexually transmitted infections are being treated. And of course we’ve already screened out everybody who’s living with HIV infection, so that tells you that that epidemic is not under control. So even a tool of modest efficacy might really help make a difference.

There are also the long-acting antiretrovirals (ARVs) in development, which my be a potential way to eliminate the reliance on daily or intermittent dosing. Are you hopeful that this could be a promising prevention option in the future?

It is going to be a better fit for some. There are lots of places—a good example is India—where we know there’s a strong preference for injectables over orals, but that varies. There are other contexts where people would rather have an oral than an injectable. I think there’s a lot of hope and enthusiasm that the long-acting ARVs are going to matter more for adolescents and young adults. If you really look at the data from both of the dapivirine ring trials and also from ATN-110 [the adolescent trials network] study that looked at young MSM [men who have sex with men] on PrEP in the US, the youngest age groups just really have trouble adhering. So we have to explore if long-acting ARVs are going to help address that problem.

I think it is also important to keep in mind that it’s not just age. In ATN-110, the Caucasian and Latino kids did just fine—they achieved basically measurable levels of Truvada, maintained them through the course of the trial, and they were protected. It was the African-American kids in the same age strata who brought down the overall curve because their uptake was so low and their adherence was so low. That tells you that it’s not just age, and it’s not biology. There are also probably socioeconomic, but certainly social and cultural barriers for subsets of people. Again, painfully, in the populations who need it most.

In the midst of all this new research, there are very ambitious goals being set by international organizations, including ending AIDS by 2030 and getting 90 percent of HIV-infected individuals on treatment. Are these goals achievable?

I’m a big believer in goals and I was turned around in some ways by this with the MDGs. I was somewhat of a skeptic early on and then I was just amazed how many ministers of health could quote for you where they were on the MDGs, if they were going to meet their targets, and which ones they were going to make and which ones they weren’t.

I started to realize people actually pay attention to this and it’s a motivator. That has a lot of value in public health, where in a world of many, many competing priorities, we’re trying to keep ministers of health, finance, and education focused on AIDS. So that’s welcome.

I think the SDGs are beautiful. We’re all worried, I think, that they are too vague and that they’re going to be harder to measure. The MDGs of course were beautifully simple.

But let me speak to a couple of issues that I think we really have to deal with. First of all, the evidence on what we really need to do for 90-90-90 is notChris-Beyrer-Humphrey-lecture clear for a number of key populations. If you think about how much more treatment there is in South Africa than there was 10 years ago, there’s just no comparison. We were in Durban in 2000 and there was essentially nobody on treatment except the rich. In 2016 when we go back to Durban, there are more people on treatment [in South Africa] than any other country in the world. It’s the largest treatment program there is and it’s enormously impressive. Yet we just talked about how high the rates of new infections are in young women and girls. So show me that this [expanded access to treatment] is really resulting in the declines in incidence that we want to see.

I think the same thing is really true when we look at the current epidemics underway in gay men. The men in the delayed PrEP initiation arm of the PROUD trial had a seroincidence of nine per 100 person-years. This is in the UK, where there’s a national health system and 85 percent of people living with HIV are on antiretrovirals. So it just really is scientifically questionable to me. Unfortunately, we’ve embraced this without understanding how high incidence still is. That’s my first critique.

The second is that this is a complex pandemic that has many different components, and all of the rhetoric about the end of AIDS and control of the epidemic presupposes that Eastern Europe and Central Asia are just taken off the table. The fact is they are taken off the table because they’re in the “too difficult” box because the Russians are such a powerful force opposing evidence-based prevention in public health. Nevertheless, those are human beings. They’re part of our world, they’re part of the AIDS epidemic, and the epidemic is expanding there. There are plenty of good reports from the same agencies who are saying we’re on the way to the end showing that the epidemic is expanding there in 2016.

The other regions where HIV is expanding is the Middle East and North Africa and that part of the world is going through a period that is really akin to World War I in Europe. It is multiple countries in rebellion, at war, and there is also a huge population displacement. There’s a long history of these kind of contexts making it virtually impossible to control infectious diseases. So I think it really is questionable what effect the 90/90/90 goals will have. I would say that we’ve made remarkable progress in the parts of the world where we have really focused attention and resources. We’ve shown that it can be done. But that’s not what much of the planet looks like.

What role do you see for an eventual HIV vaccine?

The fact that we are still seeing such high rates of incidence really speaks to the fact that primary prevention remains a challenge. And the fact that treatment is so good and this is a manageable disease, doesn’t get around the fact that it is daily lifelong chemotherapy for the rest of people’s lives. The other reality that we’re seeing where care is really good is that the long-term chronic complications of life with treated HIV disease are many and are complex. Saying that something is a chronic disease to somebody who has obesity, diabetes, hypertension, hyperlipidemia, and cardiovascular disease doesn’t sound that great. When you talk to a lot of African clinicians, people who have been in this fight for a long time, they’re thrilled that people are surviving, yet they have no idea how their health systems are going to deal with all of these aging, chronically ill people with multiple complications.

And we haven’t even gotten to half of people worldwide who need treatment. We have 37 million people living with HIV and only 17 million on treatment. So I think we need a vaccine, but I also think we can’t give up on looking for cure and remission. Even a five- or 10-years remission off therapy would make a huge difference.

Do you see a growing movement for cure research?

I think it’s a long road, but nevertheless it’s essential. I would say that it’s very clear from the IAS perspective that the young investigators, the people who are really excited about HIV research, see cure research as a really exciting prospect. I think our last six out of seven new investigator awards went to people working on reservoirs and latency. That tells you that the intellectual fire power of the next cohort of researchers is going into cure.

It also turns out that once again HIV is providing insights into other disease systems. It turns out that there’s probably a testicular reservoir with Ebola, which is why there’s sexual transmission. There’s also a reservoir with Zika, so there is also sexual transmission there. This is something we totally need to understand—how these immune-protected spaces in the CNS [central nervous system] and in the testes may really play a role in latency.

As you prepare for AIDS 2016, what do you see as the main themes for the conference?

I think the meeting in Durban in 2000 was the beginning of the treatment era. It really was a huge turning point. The world came together and really heard that it was unacceptable that the great majority of people living with this virus were going to be consigned to an early death. We came out of there with a commitment, and it took several years, but by 2003 things really began to move. And we changed the world and showed that you could treat millions of people with a complex disease in the poorest countries in the world and save lives.

In 2016, we’re really at a new point, which is: we’re not done. We have a remarkable achievement to be proud of as a movement, but we’re less than halfway there on treatment and we’re not implementing the prevention we have. We have harmful laws, policies, and practices that are aiding and abetting the virus. A proliferation of those laws in a number of countries, by the way, are going precisely in the wrong direction. We also have waning donor interest and a movement toward other priorities. I think we’ve declared victory too soon. Nobody ever wanted the end of AIDS to be the end of the AIDS response. That wasn’t the plan. And so I think that Durban in some ways has an enormous burden for us as a movement, which is to reassert the importance of continuing this work and of doing the undone work of responding to this epidemic.

Happily, I think the science really looks wonderful. This is the most competitive scientific meeting we’ve ever had. We have more than 7,000 submissions and it’s very interesting that the largest scientific component was in implementation science because so much of the field has moved toward implementation. There are a huge number of people working in that space, as there should be, and there really isn’t another venue for people to put that kind of work forward. We’re very gratified by that. We also have the largest scholarship program we’ve ever had. It’s more than twice the size of the scholarship program for our last conference in Melbourne. It is critical to figure out ways to ensure civil society continues to have access to the science.

How would you describe your tenure as IAS President?

It’s been profoundly rewarding. It’s really an honor to try and serve our community. I love the people working on AIDS—I think they’re some of the best people you can find. When I came into this leadership role there were some real challenges between governments, community, and science, and I think we’ve really worked hard to build bridges there and bring back that sense of all being in this together. That’s been very positive.

I guess the other thing I would say is I hadn’t realized how meaningful it would be for the community that I’m the first openly gay person to lead this organization. But it turns out that it really mattered to people, and so I think that that’s important too.

And Linda-Gail Bekker is going to be amazing.