You don't need to be signed in to read BMJ Blogs, but you can register here to receive updates about other BMJ products and services via our Group site.

How to Keep HIV Cure-Related Trials Ethical: The Benefit/Risk Ratio Challenge

20 Feb, 17 | by bearp

Guest Post by Nir Eyal

Re: Special Issue of the Journal of Medical Ethics on the ethics and challenges of an HIV cure

For most patients with HIV who have access to antiretroviral treatment and use it properly, that treatment works well. But the holy grail of HIV research remains finding a cure. Sometimes that means a literal, sterilizing cure that would remove HIV from the body. But increasingly the aim is to find a mere functional cure that would send HIV into sustained remission during which antiretrovirals would be unnecessary.

Early successes in cure-related research, most notably the apparent cure of ‘Berlin patient’ Timothy Brown, prompted the International AIDS Society and the US National Institutes of Health to declare cure-related research a high priority. Recent successes in animal models have re-kindled hopes, and cure-related research is ongoing.

But there is a catch. Many of the early-phase cure-related studies that are currently planned or under way carry risks that are either very high or hard to quantify. These risks come from toxicity (e.g., of stem cell transplantation in an immunocompromised population), necessary interruptions to antiretroviral treatment (either short ‘pauses’ or intentionally longer breaks), or invasive physical exams. They affect study subjects and, sometimes, third parties like sexual partners or foetuses.

While high or unknown risks are a mainstay of early-phase trials in areas like cancer research, cure study participants typically have a safe and efficacious alternative to those risks: remaining on antiretrovirals. Can we justify asking patients who are doing well on antiretrovirals to accept the risk and uncertainty of many HIV cure-related trials? If we cannot, we might need to give up on the hope of curing HIV, or of achieving controlled remission.

These ethical questions about HIV cure-related trials were first raised by an activist, then asked again and again. They also arise in human subject research beyond HIV cure-related studies: what should we do when it is hard to keep a socially-important study beneficial in prospect to study participants? Are we ever permitted to compromise the individual’s objective interests in the pursuit of collective goals? What are legitimate ways of pre-empting this dilemma? The entire February 2017 issue of Journal of Medical Ethics is dedicated to clarifying and trying to answer these questions.

After an introduction, the journal issue provides a background by leading HIV-cure related researchers Dan Kuritzkes and Kenneth Freedberg and Paul Sax, as well as myself, a philosopher. Articles by legally-trained bioethicists Rebecca Dresser and Seema Shah and philosopher Caspar Hare suggest ways to quantify and mitigate risks to participants of cure-related studies. Contributions by philosopher Lara Buchak, bioethicist and lawyer Emily Largent, and AIDS activist David Evans assess how much the potential benefits to study participants, ranging from the remote hope of being cured through financial incentives to the satisfaction of having helped others, can legitimately offset any remaining risks. Legally-trained bioethicist George Annas and philosopher Danielle Bromwich explore how much participants’ fully informed consent can count as ample protection in cure-related studies, and when that consent counts as full. Philosophers Dan Wikler, Nick Evans (with first author public health expert Regina Brown), Rahul Kumar, and Frances Kamm assess when, if ever, the potential public health benefits of research—e.g., finding a cure for HIV—can warrant placing individual study participants at high net risk. An afterword asks how these investigations should affect future directions in research ethics.

Many contributions agree that myriad ways exist to justify studies that, at least on the face of it, run counter to the best medical interests of candidate participants. Furthermore, one need not be a utilitarian to argue as much. Even so-called contractualist ethicists such as Rahul Kumar can justify such studies, provocative though they may be for current culture in clinical study oversight. That culture, these articles suggest, is hard to defend from a wide spectrum of ethical theories.


NOTE: This post will be cross-published at BMJ Opinion.

By submitting your comment you agree to adhere to these terms and conditions
You can follow any responses to this entry through the RSS 2.0 feed.

Latest from JME

Latest from JME

Blogs linking here

Blogs linking here