Kevin M. DeCock, MD, is director of the Center for Global Health at the Centers for Disease Control and Prevention (CDC), based in Atlanta. Among his past positions are Director of CDC Kenya and Director of the World Health Organization’s Department of HIV/AIDS. John Donnelly talked with Dr. DeCock Thursday about the large numbers of critical HIV research questions today, the need for a coordinated response to address those questions, and what to do about the explosion of HIV incidence among teenage girls in parts of sub-Saharan Africa discussed by Dr. Quarraisha Abdool Karim in an earlier part of this “Research Frontlines” series. This is the third part of the series, which focuses on research and the HIV epidemic.
What are your thoughts about the importance of the microbicides trials, and the impact of these trials ahead?Let’s look at microbicides more generally because at the same time that the CAPRISA results came in, yet another important trial also finished – the iPrEx study. Although we can look at these as a vaginal microbicide or an oral prophylaxis, this is really about antiretroviral-based prevention. I think we need to step back and ask the best question: How do we best use antiretroviral drugs (ARVs) for prevention and treatment for individual health as well as for public health?
There are a series of sub-questions on microbicides – about rectal microbicides, oral pre-exposure prophylaxis, the question of treatment for prevention, also the question of when to start ARVs for the individual. And there’s the whole debate about test and treat. What is needed is a much more coordinated approach, globally, to this whole list of questions. The microbicides one is a sub-component, although a very important one. We need to make sure we are being efficient for the maximum use of our resources.
You raise a number of interesting issues. What is the way ahead for coordinated research on these issues?
As I said, there is a need for coordination of the different research questions. I think that may be beginning to happen. There are discussions going on – I’ve been involved in some – within the President’s Emergency Plan for AIDS Relief (PEPFAR) and with academics to try to coordinate this more closely to ensure more transparency. What hasn’t happened is the coordination of resources. Take test and treat, for example. Different groups in different places have expressed an interest in trying to do something. This process ideally would be coordinated internationally, as not only the U.S. is putting money into research. It’s important we all are in the same boat and we’re working efficiently.
Is it an inefficient moment?
Not yet. We should be sure it doesn’t become one.
On microbicides, what’s ahead?
As far as microbicides research is concerned, the male circumcision experience offers somewhat of an example for a potential pathway. You normally need more than one trial to develop global policy, so it will be important to get another result that corroborates this initial information. What needs to happen is international bodies responsible will develop normative guidance – the World Health Organization, UNAIDS – with involvement from PEPFAR, CDC, the National Institutes of Health, and other partners who come together to review the evidence. The process for developing policy and developing guidance goes from there. This applies equally to the microbicides decision as it does to the oral pre-exposure prophylaxis, but the difference on the pre-exposure prophylaxis is that those drugs are currently available. We may see individuals acting in the absence of normative information.
How much of a worry is that?
It is cause for concern because there is potential that some people who unknowingly have HIV are taking these drugs in ways that aren’t suppressive, and this could lead to resistance.
Dr. Quarraisha Karim’s interview yesterday in Science Speaks dealt in part with the alarmingly high HIV prevalence among teenage girls in South Africa. She is calling for much more robust efforts to protect them as well as setting up a better system for involving them in research. Your thoughts?
I would generally support a more robust response for different reasons. One is the sheer epidemiological data. When you look at age-specific prevalence in boys and girls, there is this astonishingly steep increase in HIV prevalence, meaning a stunningly high HIV incidence, in girls. You go from 12 to 13 year-olds with almost no HIV infection to the early 20s with more than 20 to 25 percent infected. It’s remarkable and awful. What are the dynamics of all that? Who is infecting whom? What are the circumstances? I don’t think we understand it completely. It needs to be understood on so many levels, biologically, anthropologically, socio-economically. Conventional wisdom is that since HIV prevalence in young men is lower, many of these girls are presumably infected by older men. I think we need to explore that.
On the socio-economic side, there are now a number of studies looking into it. CDC was involved in one in Swaziland, on sexual violence against girls. It found really astonishingly high rates of sexual violence, where a third of women reported that at some stage of their lives, they were coerced into sex or were the subject of sexual violence. What it raises is a need for those affected societies to examine societal norms. This is the sort of situation where structural interventions and social determinants are much more powerful than any specific biomedical intervention. Society needs to say this is not acceptable. It is an extraordinary situation when you think about it, although it is not unique and exists in other parts of the world, such as sexual violence in the Eastern Congo. These are structural society issues, where social change is absolutely necessary.
What about the ethical limitations in conducting HIV research with minors?
Quarraisha Karim is correct in saying we are the victims of doing the right thing, protecting adolescents in research. The most vulnerable population has been excluded in research. It is something that needs to be addressed.
What needs to happen?
For HIV prevention research, for pre-exposure prophylaxis trials, or microbicides trials, we need to be setting it up so that adolescents can be enrolled in these trials, while at the same time be adequately protected and are assured informed consent. This is a specialized aspect of the whole challenge HIV poses in pediatric and adolescent medicine. A simple thing like HIV testing is complex when dealing with children and adolescents, so dealing with consent or the concept of assent is even more difficult. Who can give consent for a minor who is not legally an adult? There are different regulations and different laws in countries.
What about the ethics about doing clinical trials in developing countries generally, an issue that is now being studied by the Presidential Commission for the Study of Bioethical Issues?
I think the HIV model has worked relatively well. The rest of the infectious and non-infectious diseases world could learn a lot from that experience. We’ve had very good malaria work done, and very good TB work. I do believe we have an obligation to do this work in the areas where the need is most pressing.
In all of the discussions, of course, is what should be the minimum standard of care for participants, and what should happen to the population after the end of the trial. We had these discussions years ago, in the 1990s, in trials regarding prevention of HIV transmission from mother to child.
Ahead, for HIV, the ethical questions are going to be different. Now that we have effective biomedical interventions, what should be the standard of care in prevention trials for any new intervention? It will become increasingly difficult to do a trial because of the number of different interventions available that could be delivered as a standard of care. Suppose we want to do a trial in South Africa for a new HIV vaccine. Traditionally, you do a placebo control. Today, with everything available, you don’t just have a placebo, but we also provide counseling and condoms, for example. But we also have more – male circumcisions, microbicides, pre-exposure prophylaxis. So what should be offered to the participants in addition to the vaccine? It may be that the trial would have to be so big that it simply is not doable. That’s an interesting discussion.