In a revolutionary approach to curing HIV, amfAR is soliciting “novel, high-risk, and potentially high-impact” proposals from bioengineers to address the main barrier to a cure: persistent reservoirs of virus not cleared by antiretroviral therapy (ART).
The aim is to foster innovative collaborations between HIV cure researchers and bioengineers —scientists who use engineering principles to solve medical problems, including disease diagnosis and treatment.
“This is a bold Request for Proposals,” said amfAR’s Dr. Marcella Flores, associate director of research. “We are looking for the most cutting-edge research and technologies that have never before been tested in HIV.”
The Investment Grants provide funding of up to $1.5 million over four years in three phases and are part of amfAR's $100 million Countdown to a Cure initiative, aimed at developing the scientific basis of a cure by 2020.
Applicants must be HIV scientists, who are required to work with bioengineers to explore curative approaches to HIV. Those include the elimination or permanent disabling of the reservoir and the discovery of other mechanisms that would result in ART-free remission without the risk of transmission for at least five years. The deadline for letters of intent is September 27.
The funding is based on milestones, which means researchers must show that they were successful in one phase of the project before moving on to the next.
The goal of each area of interest is to develop tools or produce information that will be crucial for Phase 1 clinical trials at the end of the four years,” Flores said. “So while we are encouraging groundbreaking, early stage approaches, we also want something that will yield tangible results within a given timeframe.”
Flores said the inspiration for the RFP was a bioengineering friend who had responded to a request for proposals from DARPA (Defense Advanced Research Projects Agency), which was established in 1958 under the Department of Defense and makes pivotal investments in breakthrough technologies for national security. Although little known by the general public, DARPA has a reputation for pioneering some of the most revolutionary technology since the Mercury-Gemini-Apollo era, such as the Internet, automated voice recognition and language translation, and GPS.
“They solicit the most cutting-edge research, things you would see in Sci-Fi movies, and do so in a very focused and deliberate manner,” Flores said. “We wanted to create an RFP that was similar but with enough elbow room so that we could receive ideas and approaches that we hadn’t thought of.”
Flores, who has a background in viral immunology, looked at the most respected bioengineering schools to identify their top faculty, who was publishing their work, what technologies were being explored and what was being tested and used on diseases. For example, she came across a physician and engineer at MIT who had developed a synthetic biomarker for better detection of blood clots using a simple urine test. Could something similar be used to identify and eradicate the HIV reservoir?
“We wanted to really make sure that we did not just get every technology under the sun but really narrow it to questions we thought were required to cure HIV,” she said. “So we came up with three specific areas of interest.”
The three areas are:
- Biomarkers or molecular signatures — indicators of disease — that can distinguish the reservoir from uninfected cells in vivo during suppressive ART
- Mechanisms to induce cell death specifically in HIV-infected cells in vivo; and
- Mechanisms to permanently disable the provirus in vivo
Biomedical engineers are playing an increasingly important role in solving complex medical problems, said Dr. Kaiming Ye, professor and chair in the department of biomedical engineering at Binghamton University, in part because of advanced cell biology and the successful mapping of the human genome, which can unlock potential cures to disease. For example, in the field of HIV, they may focus on using nanotechnology to improve the delivery of ART, he said.
Dr. Thomas Hope, a professor of cell and molecular biology at Northwestern University’s Feinberg School of Medicine and a member of amfAR’s Scientific Advisory Committee, highlighted the innovativeness of “bringing in new minds, new ideas, and new approaches” to advance HIV cure research at a quick pace.
“The other thing that’s great is the three phases, which allows you to take these high-risk approaches without having funds directed towards non-productive lines of investigation,” he said.
These kinds of partnerships are the future of HIV cure research, said Dr. Daniel Douek, chief of the Human Immunology Section of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases and chair of amfAR’s Scientific Advisory Committee.
“I see this call for proposals to partner cure scientists with engineers as sort of a natural evolution of our cure work into what the future of biomedical scientific research will be,” he said. “Not only is it innovative, it is leading the way.”