The Ethics of HIV Cure Trials

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AIDS activist Peter Staley was diagnosed with HIV in 1985, and for decades he thought he would never live to see a cure. But with recent advancements in gene editing, therapeutic vaccines and other promising approaches to curing HIV, Staley now believes that a cure during his lifetime might just be possible.

Basic science research has yielded promising results in laboratories, and isolated cases of in-human cures (or at least prolonged remissions) have given scientists new insights on a path forward, according to researchers and physicians at the recent New York State 2016 HIV Cure Symposium, organized by Mount Sinai's Institute for Advanced Medicine.

Terri Wilder, director of HIV/AIDS Education and Training at Mount Sinai, organized the Cure Symposium precisely because medical providers need to start thinking critically about how HIV cure research and will impact their patients' lives.

"Once the cure puzzle is figured out and is widely distributed, a medical provider will be the gatekeeper," Wilder said. "So thinking about this now prepares providers in New York state."

The next step is to cautiously test some of these approaches in patient volunteers, and early phase clinical research trials are cropping up across the globe. While exciting, the shift from laboratory to human testing in HIV cure research is fraught with important ethical considerations, according to researchers gathered at the Cure Symposium.

Current antiretroviral therapy (ART) helps people with HIV live long and healthy lives, often with a simple once-daily pill. One of the main goals of HIV cure research is to find a treatment that would allow patients to stop ART for years -- ideally forever -- much like the new hepatitis C medicines that can cure patients after a few months of treatment.

But when it comes to clinical trials for HIV cures, many patient volunteers may be asked to stop taking their once-daily medicines to measure the true effect of the experimental treatment.

"HIV treatment has raised ethical questions from the very beginning of the epidemic," said Stuart Rennie, Ph.D., associate professor of social medicine at the University of North Carolina School of Medicine, Chapel Hill. Cure trials are particularly problematic because "treatment interruptions are contrary to clinical care," Rennie said, noting that early phase HIV cure trials carry an unknown risk with still-murky benefits to patients.

And the risk of stopping ART is very real. In 2013, two bone-marrow transplant patients in Boston were declared "cured" of their HIV. They stopped taking ART, and by 2014 both had relapsed with dire health consequences. It's the "nightmare" scenario that nobody wants to unfold during a clinical trial, said Steven Deeks, M.D., professor of medicine at the University of California, San Francisco.

HIV cure trials carry a difficult balance of risks and benefits, said Antonio Urbina, M.D., associate professor of medicine at the Icahn School of Medicine, Mount Sinai Health System. Currently available ART is "almost good enough," while current cure treatments are "not really ready for prime time."

Still, "patients are willing to put themselves out there for the opportunity to be cured," Urbina noted, and the burden is on the scientific community to ensure that the trials are well designed and patients are properly informed of the risks.

"As someone who has gone through blips and treatment failure, I'm not scared of a little virus," said AIDS activist Peter Staley. For treatment-experienced people like himself, Staley believes there is a "built in eagerness" to participate in research that might one day lead to a cure.

Another layer of ethical consideration is protecting the sexual partners of clinical trial participants. Structured treatment interruptions raise the possibility that the HIV-positive person could infect a partner -- a person who is not involved in the research and has not consented to the risks involved, Rennie explained.

According to Steven Deeks, trials must be built with disclosures and additional safeguards, such as pre-exposure prophylaxis (PrEP) and condoms, that will help protect partners from possible infection, which "really reflects how we've shifted to a public health model" in the research community.

For Wilder, discussion about a cure should be housed within the broader goal of ending HIV all together. "As we're talking about ending the epidemic in New York state, cure should be part of the conversation," she said.