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MERIT grant awarded to study cure for HIV

2025-08-28
(Press-News.org) Nearly 20 years ago, a man named Timothy Ray Brown who was living with HIV and cancer, underwent two courses of stem cell transplantation to treat his acute myeloid leukemia. By using donor cells that lacked a key molecule needed for HIV to enter and infect immune cells, the procedures not only led to remission of his cancer, but also cured him of HIV.

Now, a scientific team co-led by Dr. Lishomwa Ndhlovu at Weill Cornell Medicine and Dr. Jonah Sacha at Oregon Health & Science University have received an NIH MERIT Award to provide long-term grant support to study a handful of people who, like Brown, have managed to clear HIV after a stem cell transplant and those who did not. The goal of the investigation is to figure out why the approach worked—and how to transform it into a broadly applicable immunotherapy for eliminating HIV.

“We are laser focused on figuring out a cure for HIV,” said Dr. Ndhlovu, the Herbert J. and Ann L. Siegel Distinguished Professor of Medicine in the Division of Infectious Diseases at Weill Cornell Medicine. Although bone marrow transplantation has proven in a small number of cases to eradicate the virus, the procedure is physically grueling, can be associated with significant complications and even death, and—from the standpoint of clearing HIV—not always a success. “We therefore want to direct our efforts at conducting mechanistic studies to identify and better understand the immune responses that, in these individuals, mediated a cure in some but not others,” he said.

The grant, awarded by the National Institute of Allergy and Infectious Diseases, will provide Dr. Ndhlovu and Dr. Sacha, a projected $8.2 million in funding over five years—with a potential for renewal to 10 years.

“The first step is to understand how each of these individuals were cured,” said Dr. Sacha, professor and chief of the Division of Pathobiology and Immunology at OHSU’s Oregon National Primate Research Center.

At Weill Cornell, Dr. Ndhlovu and his colleagues will adopt multiple approaches to investigate the mechanism of HIV eradication. First, they will study samples from individuals for whom the stem-cell transplants were successful and from others that were not cured by the procedure.

“I hope that by looking at our cells, scientists can find the missing piece of the puzzle so they can recreate a cure without the need for a stem cell transplant,” said Marc Franke, who underwent the procedure to treat his leukemia in 2013.

“These participants have already contributed greatly to science,” noted Dr. Ndhlovu. To determine whether the transplant eliminated HIV, they had to stop taking their antiviral medication. All have now been HIV-free for years.

"I understand my responsibility to science­—with my cure hopefully serving as a blueprint for immunotherapy—and the impact these HIV cure research efforts could have in years to come,” said participant Adam Castillejo, who was the second person with HIV to publicly disclose his cure after a stem cell transplant to treat his cancer. “As the torch bearer, passed on from Timothy Ray Brown, and now as a Global HIV Ambassador, I believe this collaboration is essential to put an end to the AIDS pandemic."

Identifying the immune mechanisms that can clear HIV during the stem cell transplantation, the researchers will study blood samples from these participants to determine the mechanisms that led to the elimination of HIV.

Once the researchers determine the responsible immune mechanisms for clearing HIV throughout the body, they will test whether an immune based infusion in preclinical models can replicate the process. The Weill Cornell team has developed a mouse model in which to examine how human immune cells attack HIV and the investigators at OHSU have established a non-human primate model in which they have been able to successfully recreate the virus-clearing transplants.

The researchers can then work on developing a type of immunotherapy that is primed to target HIV-infected cells in humans.

“We are excited for the opportunity to continue to work with these remarkable survivors who have endured so much and have been so integral to advancing science,” Dr. Ndhlovu said.

For their part, the participants express a similar desire to do what they can to help expand the ranks of those who have been cured of HIV. 

“I felt it was important to participate because this journey is not just about me,” said Paul Edmonds, who had been living with HIV for more than 30 years before his cancer diagnosis in 2019. “This research represents hope for millions of people living with HIV worldwide. It shows that a cure is possible and that we must continue searching for answers. My hope is that these studies will lead to a treatment that will eradicate the virus once and for all.”

END


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[Press-News.org] MERIT grant awarded to study cure for HIV