Oregon Health & Science University scientists have received $8.4 million from the National Institute of Allergy and Infectious Diseases to develop a cure for HIV by studying three of the only ten people ever known to be cured of the virus. The five-year grant, designated as a MERIT award with potential for five-year extension, will fund research into how Adam Castillejo, Paul Edmonds, and Marc Franke cleared HIV from their bodies following stem cell transplants for cancer treatment.
Studying the Rare Cases of HIV Cure
The research team, led by co-principal investigator Jonah Sacha, Ph.D., professor and chief of the Division of Pathobiology and Immunology at OHSU's Oregon National Primate Research Center and Vaccine and Gene Therapy Institute, will collaborate with scientists at Weill Cornell Medicine to understand the precise mechanisms behind these extraordinary cures.
"The first step is to understand how each of these individuals were cured," Sacha explained. While the team knows the men cleared HIV through stem cell treatment for cancer, the exact mechanisms remain unclear.
The three participants represent remarkable cases in HIV research. Adam Castillejo, initially known as "The London Patient," was cured following a 2016 stem cell transplant for non-Hodgkins lymphoma. Marc Franke from Germany marked 12 years since his curative transplant, while Paul Edmonds received his life-saving treatment at City of Hope near Los Angeles in February 2019 for acute myeloid leukemia.
Developing a More Accessible Treatment
Current stem cell transplantation requires intensive therapy with a donor match and lengthy recovery periods. The research aims to develop a more broadly applicable treatment. "We believe a treatment could emerge from this research that would be more broadly applicable than stem cell transplantation," Sacha said. "Long term, this research could lead to a single infusion where a patient could be done after a weeklong stay at a clinic."
The study will include comprehensive medical examinations and white blood cell sampling to define the cure mechanisms. Researchers will compare data from the three cured individuals with information from nonhuman primates cured of the monkey form of HIV, as documented in a 2023 study.
Clinical Trial Timeline and Global Impact
The research progression will move from developing an infusion-based treatment in mice to testing in nonhuman primates before advancing to human clinical trials. "In a best-case scenario, assuming it's safe and well-tolerated, a clinical trial may be possible in five years," Sacha stated.
The potential impact is enormous, given that HIV affects an estimated 40 million people worldwide and continues to kill more than 600,000 people annually. Current antiretroviral therapy, while effective at suppressing viral load, requires lifelong treatment and can cause long-term health complications including increased cancer risk, opportunistic infections, diabetes, cardiovascular disease, and reduced lifespan.
Patient Advocates for Research
All three cured individuals have committed to participating in the research as advocates for the global HIV community. Castillejo, diagnosed with HIV in 2003, has become an Ambassador of Hope, stating, "It was like winning the lottery. I feel like I've had a second chance at life, so I've dedicated myself to being a global ambassador for HIV."
Edmonds, who lived with HIV since his 1988 diagnosis, emphasized the global need: "My hope is that it will lead to a cure for everyone around the world. The antiretroviral medications can be hard to come by elsewhere in the world and a cure would do away with that."
Franke, celebrating what he calls his "12th birthday" since his transplant, stressed the importance of global thinking: "We learned from the coronavirus pandemic that you can't think only of your country when it comes to a virus. You have to think globally."
Research Methodology and Collaboration
The study will be conducted in collaboration with Lishomwa Ndhlovu, M.D., Ph.D., the Herbert J. and Ann L. Siegel Distinguished Professor at Weill Cornell Medicine. "We are uniquely positioned to figuring out a cure for HIV individuals by studying those whom the stem-cell transplants were successful and from others that were not," Ndhlovu explained.
The research will examine both the specific genetics of each individual and identify commonalities that could be developed into a generalized HIV cure. Some of the cured patients received stem cells from donors carrying a rare variant of the CCR5 gene that prevents viral infection, while others were cured despite their donors lacking this genetic protection, suggesting additional mechanisms at work.
Sacha expressed confidence in the research timeline: "I actually think that we are, I think within our lifetimes, for sure, we will see a cure for HIV. Of this, I am confident."
