Exploring the Complex Ethics of HIV Cure-Related Research
A cure for HIV infection has been a long-term goal since the virus first was identified in the early 1980s. Since then, an HIV cure has moved from the aspirational to the theoretically plausible, particularly following the elimination of Timothy Ray Brown’s latent HIV. Still, 36.7 million people live with HIV worldwide — 1.2 million of them in the United States External link — and finding a cure isn’t easy due to the scientific realities and ethical dilemmas involved in this type of research.
Karine Dubé, DrPH, research assistant professor in the University of North Carolina at Chapel Hill’s Gillings School of Global Public Health, hopes to make sure the right voices are heard by taking a community-based approach to her social sciences and ethics research around HIV.
“We have to make sure that the people who enroll in HIV cure-related research are a reflection of the epidemic in the community,” Dubé said in an interview.
Partnering with diverse groups of professionals beyond biomedical researchers helps shed light on the issues that affect people living with HIV. From the ethical parameters of asking patients to stop taking HIV medication in order to participate in some HIV cure-related protocols, to issues regarding the standard of care and community involvement, Dubé’s research has zeroed in on some of the most pressing concerns for the HIV community.
In an interview, she discussed the value of being community-focused while drawing from her social sciences research to highlight the complexities and risks involved in finding an HIV cure.
Let’s start by talking about the complex topic of HIV cure-related research. This kind of work requires biomedical research and input from ethicists, social scientists and community engagement leaders. How do you involve all these varying fields?
HIV cure-related research is unique because it is conducted against a background of highly effective antiretroviral therapy. In other words, finding a cure for HIV infection will involve introducing possibly risky interventions in individuals who already are enjoying an almost normal life expectancy. So, there’s a tremendous amount of altruism that goes on in these early-phase HIV cure-related studies.
We need to start appreciating these studies from the patient/participant perspective, particularly as the Food and Drug Administration recently launched a Patient-Focused Drug Development Initiative to help make these studies more acceptable to people living with HIV. That’s where my work primarily is focused — looking at potential HIV cure-related research strategies from the patient and participant perspective.
Asking a person with HIV who is on antiretrovirals and doing well to interrupt treatment to participate in HIV cure-oriented research presents a lot of ethical questions. What are the motivations and incentives for those participating in HIV cure-oriented research?
There’s a tremendous amount of altruism involved. People want to help advance HIV cure-related science. Some participants express the realization that if they are alive and doing well today, it’s because other people volunteered in HIV-related trials before them. We have come a long way in 37 years of knowing about HIV, and the next phase will be to find a cure, or at least an intervention or combination of interventions that will permit people to stay virally suppressed while off HIV treatment.
While there are very altruistic participants who want to help advance the science, it is important to remember that not every HIV cure-related study requires analytical treatment interruptions. Only a very few HIV cure-related studies require treatment interruptions at this time, and these are conducted in carefully controlled research environments with close monitoring.
We still need to make sure that there are safeguards in place in all studies, particularly those that do require analytical treatment interruptions — I co-authored a recent paper that highlights some of these safeguards. I’m also really interested in the ethics of translating novel HIV cure-related research into human studies for the first time (e.g., first-in-human studies), and in the ethics of combining various HIV cure-related strategies. In the future, I also think we will need to integrate ethics as part of actual HIV cure clinical studies.
What has been the biggest takeaway from your research into the ethics of HIV cure-related research? Was there something that really surprised you?
When we start looking into the topic of HIV cure-related research, we quickly realize that there are potential unintended consequences. Inherently, a cure would be a great thing, but when we start introducing social sciences and ethics, we see that it’s such a complex issue. That’s why we need social sciences and ethics to complement the biomedical research that’s happening, and not be an afterthought.
Most of the efforts right now are based in basic science and early-phase biomedical clinical trials. It’s critically important to start asking about possible attributes of a potential future HIV cure regimen that people living with HIV would find desirable, and about the critical safeguards that should be in place to move the research forward from a regulatory perspective. We also should consider what information is needed to keep communities engaged in sustained dialogue along the way.
Why is ethical HIV cure-related research so important for the public health community? How does your research relate to the larger medical community?
It’s important to incorporate a public health perspective to HIV cure-related research because we need to start thinking about translating novel discoveries into human studies, scaling up interventions, and possibly conducting future downstream implementation in the real world. HIV cure-related research involves an interesting interconnection between public health ethics, medical ethics and research ethics. It raises all sorts of ethical questions. For example, one of the major issues being discussed right now is — in the context of “U equals U,” which means undetectable HIV is untransmittable — what would a viral rebound mean for a person who is used to being undetectable for HIV infection?
What this means is that someone could transmit HIV unknowingly while doing a study involving an analytical treatment interruption, so we need to ensure that standards of prevention are met not only for the study participants, but also for their sexual partners. There are all kinds of public health implications that we need to start considering. There also could be other risks. For example, there could be unsuspected drug resistance that could spread during an analytical treatment interruption. We also should think about issues of scalability and implementation.
In public health, we use a team science approach. We bring people together: biomedical cure scientists, community members, ethicists, social scientists and regulators. The field of public health makes it possible to apply that unique team science and a systems-thinking perspective. We all should be working on this together.
What are some of the challenges of working across teams that include researchers, ethicists, community advocates and public health officials? How do you work together toward the goal of an HIV cure (or viral suppression off treatment)?
Ideally, there would be an interdisciplinary team around each specific HIV cure-related study. For example, in addition to the biomedical HIV cure researchers, there could be community representatives, social scientists, ethicists and mental health professionals. We are starting to embed social sciences and ethics as part of actual HIV cure-related studies. The AIDS Clinical Trials Group study, which involves an intensively monitored antiretroviral pause. The Last Gift study is another example of successful integration between the various sciences.
We also need to start engaging HIV care providers in the conversation to ask what their perceptions of a potential cure would be. Not all of them are excited about the idea of having their patients interrupt their HIV treatments, for example. There has to be a dialogue between biomedical researchers, regulators, HIV care providers, community representatives and social scientists to discuss possible guidelines and parameters.
How do you maintain this close relationship with the community when doing HIV cure-related research?
The community should be involved at every step of the research process, from design to implementation and data dissemination. We also need to translate complex HIV cure science to the community. This is one of the reasons why we developed the CUREiculum as a community literacy tool around HIV cure research. Community involvement is one of the critical safeguards in clinical research. In the social sciences, my co-investigators are community representatives. HIV cure-related research has to be conducted in a similar way, as a real partnership with the community.
It’s vital to involve all the key players, otherwise we may be missing important voices — particularly the voices of people living with HIV who will be the potential end users of these interventions. The right people need to be at the table, providing input, from the beginning.
This interview was edited for clarity and brevity.
Citation for this content: MPH@UNC program