A new NIH-funded initiative aims to transform rare HIV cures into broadly accessible immunotherapies, leveraging lessons from the few individuals who have cleared the virus after stem cell transplants.
Nearly two decades ago, Timothy Ray Brown, living with both HIV and leukemia, underwent two stem cell transplants using donor cells lacking a key receptor HIV uses to infect immune cells. The procedure not only put his leukemia into remission but also eradicated his HIV, offering a rare glimpse at a functional cure.
Now, a research team co-led by Dr. Lishomwa Ndhlovu of Weill Cornell Medicine and Dr. Jonah Sacha of Oregon Health & Science University has received a prestigious NIH MERIT Award to study why similar transplants have cured some patients but not others. The goal is to identify immune mechanisms that could guide development of an HIV-targeted immunotherapy.
“We are laser-focused on figuring out a cure for HIV,” said Dr. Ndhlovu, Herbert J. and Ann L. Siegel Distinguished Professor of Medicine at Weill Cornell. “Bone marrow transplantation has eradicated the virus in a small number of cases, but it’s physically grueling, carries serious risks, and doesn’t always succeed. Our focus is on understanding the immune responses that mediate a cure in some patients but not others.”
The grant, awarded by the National Institute of Allergy and Infectious Diseases, provides $8.2 million over five years, with potential renewal up to a decade.
“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.
At Weill Cornell, Dr. Ndhlovu’s team will analyze blood samples from patients whose transplants succeeded and from those who were not cured. The researchers hope to pinpoint the missing pieces of the immune puzzle that could enable replication of a cure without the need for risky stem cell procedures.
“By studying these cells, scientists may eventually recreate a cure without requiring a transplant,” said Marc Franke, who underwent a stem cell procedure for leukemia in 2013.
Participants have contributed to science by discontinuing antiviral therapy under medical supervision to confirm the virus’s elimination. Adam Castillejo, the second publicly cured individual after Brown, described his role as carrying forward a “torch” to advance HIV immunotherapy research.
The team will use preclinical models, including humanized mice at Weill Cornell and non-human primates at OHSU, to test whether immune-based infusions can replicate the virus-clearing effect of transplants. These studies aim to pave the way for immunotherapies capable of targeting HIV-infected cells in humans.
“We are excited to continue working with these remarkable survivors, whose experiences have been critical to advancing science,” Dr. Ndhlovu said.
For participants like Paul Edmonds, living with HIV for more than 30 years before a cancer diagnosis, involvement in the research is deeply personal. “This journey is not just about me,” Edmonds said. “It represents hope for millions of people worldwide and reinforces that a cure is possible.”
