Adam Castillejo, Paul Edmonds and Marc Franke live a world apart, yet they share one infinitesimally rare trait: Each of them literally embodies the cure for HIV.
Although HIV can now be managed over a lifetime of antiretroviral therapy, which suppresses the viral load, there is no definitive therapy to entirely rid the body of a virus that affects an estimated 40 million people worldwide — with a tiny number of notable exceptions.
In the coming year, three of them will gather to officially begin a unique scientific collaboration.
The three men, along with a scientific team led by researchers at Oregon Health & Science University, Weill Cornell Medicine and other institutions across the world, will set out to learn exactly how each of them cleared the virus after they happened to undergo stem cell transplants for cancer. In doing so, the researchers and the participants see the possibility of developing a single infusion that could cure millions and ease the burden of a disease that continues to kill more than 600,000 people per year worldwide.
“The first step is to understand how each of these individuals were cured,” said 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.
The team has been awarded $8.4 million from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Sacha will work with collaborators at OHSU as well as Weill Cornell Medicine during the initial five-year life of the grant. In addition, the NIH has designated the grant as a MERIT award, enabling Sacha and collaborator Lishomwa Ndhlovu, M.D., Ph.D., of Weill Cornell to extend the award an additional five years.
Sacha and his collaborators already know the men cleared HIV from their body through a stem cell treatment for cancer, but it’s not clear how exactly the treatment worked.
“We believe a treatment could emerge from this research that would be more broadly applicable than stem cell transplantation, an intensive therapy that requires a donor and a lengthy and intense recovery,” 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.”
Clinical trial may be five years awayTo that end, the research will include medical examinations including sampling white blood cells to better define the mechanism of how it happened.
“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,” said Ndhlovu, who is the Herbert J. and Ann L. Siegel Distinguished Professor and professor of immunology in medicine in the Division of Infectious Diseases at Weill Cornell Medicine.
The team will compare data derived from Castillejo, Edmonds and Franke with data collected through a similar examination of a pair of nonhuman primates cured of the monkey form of HIV, first examined in a study published in 2023.
Finally, the group will develop an infusion-based treatment in mice and then in nonhuman primates. If the treatment proves safe and effective in nonhuman primates, the next step would be advancing the therapy toward clinical trials in people.
“In a best-case scenario, assuming it’s safe and well-tolerated, a clinical trial may be possible in five years,” Sacha said.
Three people who already embody the cure will come together to kick off the initiative.
‘Like winning the lottery’
As the second person in the world known to be cured of HIV, Adam Castillejo initially opted to remain identified only as “The London Patient.”
That changed for the British-Venezuelan once he began to see the public outpouring of interest and support. Despite the societal stigma that continues to shadow the virus, Castillejo knew that his stem cell treatment for non-Hodgkins lymphoma in 2016 represented a milestone for millions of people worldwide with HIV.
Castillejo, 45, decided he wanted to be an Ambassador of Hope.
“It was like winning the lottery,” he said. “I feel like I’ve had a second chance at life, so I’ve dedicated myself to being a global ambassador for HIV.”
Participating in the new U.S. study reflects his determination to do all that he can to assist scientists working to cure and ultimately eradicate a virus that continues to affect millions, including children born with HIV.
Diagnosed with HIV in 2003, Castillejo benefited from antiretroviral therapies developed decades before.
“I’m alive today because some scientists 20 or 30 years ago went on a quest to find a cure,” he said. “We need to find a cure for everyone.”
Castillejo is eager to participate in the new U.S. study with the hope that scientists can develop a cure that’s enduring worldwide. He has faith in Sacha as part of the next generation of scientists committed to bringing an end to HIV.
“He’s a very passionate scientist who believes he can help our community,” Castillejo said. “I believe in him, and I believe he will find a cure.”
‘A new life’
Earlier this year, Marc Franke marked 12 years since he received the stem cell transplant that treated his cancer immediately and eventually enabled him to discontinue antiretroviral therapy for HIV — because he no longer needed it.
In effect, he calls it his 12th birthday.
The 56-year-old from Velen, Germany, wants to share his story as a cause for hope for millions of people around the world who are still living with HIV and more at risk of contracting it.
“The stem cell transplant was the beginning of a new life,” he said. “Without it, I would not be sitting here.”
He’s grateful for the stem cell donor who carried a relatively rare variant of the CCR5 gene, which prevents the virus from infecting his cells. In fact, he’s gotten to know his donor, who has joined him to celebrate his transplant anniversaries. But he also knows there are other patients who were cured even though their stem cell donors did not carry the homozygous version of the variant, meaning there’s a missing puzzle piece to solve.
His goal is to provide all the support scientists need to discern the missing piece or pieces to curing a disease that remains heavily stigmatized more than four decades after it emerged.
Eradicating the virus is the best way to eliminate the stigma, he said.
“We learned from the coronavirus pandemic that you can’t think only of your country when it comes to a virus,” Franke said. “You have to think globally.”
‘A cure for everyone’
Paul Edmonds, now 69, remembers his mind flashing to Timothy Ray Brown when he learned about the possibility of getting a stem cell transplant from a donor to treat an aggressive form of cancer called acute myeloid leukemia.
Brown, originally known as the Berlin patient, passed away in 2020, but not before making history as the first known person to be cured of HIV.
When Edmonds received his stem cell transplant at City of Hope near Los Angeles in February 2019, he, too, became a cause for hope that it may be possible to end the HIV epidemic. He’s encouraged that the research beginning now could lead to a straightforward treatment that vastly expands the number of people who no longer have to think about the virus.
“My hope is that it will lead to a cure for everyone around the world,” he said.
Edmonds lived with HIV since being diagnosed in 1988, but he knows the antiretroviral therapies aren’t readily available for everyone worldwide. And, even though they’ve improved across decades, they can still be toxic for some people, especially over time.
“The antiretroviral medications can be hard to come by elsewhere in the world and a cure would do away with that,” he said. “Even in the U.S., it means that people wouldn’t have to start on extended medications for their whole lives and endure the damage that does over time.”
Thirty-five years after he began antiretroviral therapy, he is relieved to be done with it.
That’s because for Edmonds and millions of others who continue to undergo antiretroviral therapies, ongoing treatment is itself a burden that leaves individuals more prone to cancer, opportunistic infections like pneumonia, diabetes, cardiovascular disease, early aging and reduced lifespan.
Source: OHSU