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OHSU study provides clues to broader HIV treatment potential for people

OHSU study provides clues to broader HIV treatment potential for people


Dr. Jonah Sasha, a researcher at Oregon Health and Science University, led a non-human primate study that helped explain how five people who received stem cell transplants were cured of HIV. The findings may bring scientists closer to developing what they hope will be a broader treatment for the virus that causes AIDS.  (OHSU/Kristin Torres Hicks)

Dr. Jonah Sasha, a researcher at Oregon Health and Science University, led a non-human primate study that helped explain how five people who received stem cell transplants were cured of HIV. The findings may bring scientists closer to developing what they hope will be a broader treatment for the virus that causes AIDS. (OHSU/Kristin Torres Hicks)

A new study from Oregon Health and Science University helps explain why at least five people have been freed from HIV infection after receiving a stem cell transplant. The study’s insights may bring scientists closer to developing what is hoped to be a broader treatment for the virus that causes AIDS. 38 million people worldwide.

Published in today’s magazine immunity, an OHSU-led study describes how two non-human primates were cured of simian HIV after undergoing stem cell transplantation. He also reveals that two conditions must coexist for treatment to occur, documenting the order in which HIV is cleared from the body. This detail can inform efforts to make this treatment available to more people.

“Five patients have already demonstrated that HIV can be cured,” said the study’s principal investigator. Dr. Jonah SashaProfessor of the Oregon National Primate Research Center and Vaccines and Gene Therapy Institute at OHSU.

“This study will help us understand the mechanisms that enable that therapy,” Sacha continued. “We hope our findings will help make this treatment effective for everyone, ideally with a single injection rather than a stem cell transplant.”

The first known HIV can be cured by stem cell transplant A man who had lived with HIV was also diagnosed with acute myeloid leukemia, a form of cancer, and underwent a stem cell transplant in Berlin, Germany. stem cell transplant, also known as a bone marrow transplant, is used to treat some forms of cancer.known as Berlin patienthe received a stem cell donation from someone with a mutation. CCR5 This gene normally encodes a receptor on the surface of white blood cells that HIV uses to infect new cells.a CCR5 Mutations make it difficult for the virus to infect cells and can make people resistant to HIV. Since the Berlin patient, four more have been similarly cured.

This study was conducted using a non-human primate species known as the Mauritian cynomolgus monkey. previously demonstrated You can have a successful stem cell transplant. All eight study subjects were HIV-infected, four of whom received stem cell transplants from HIV-negative donors, and the other half who did not receive transplants as study controls.

Two of the four transplant recipients were successfully treated for graft-versus-host disease commonly associated with stem cell transplantation and were cured of HIV.

Dr. Richard Maziartz

Dr. Richard Maziartz (OHSU)

Other researchers have used similar methods to cure HIV infection in nonhuman primates, but this is the first time that a research animal cured of HIV has survived for a long time. Nearly four years after the transplant, both are alive and HIV-free. Dr. Sasha said they survived thanks to the exceptional care of veterinarians at the Oregon National Primate Research Center and the support of study co-authors, two clinicians at OHSU who care for people undergoing stem cell transplants. It is said that Richard T. Maziartz, M.D.and Dr. Gabriel Myers

Dr. Gabriel Myers (OHSU)

Dr. Gabriel Myers (OHSU)

“These results highlight the power to combine clinical studies in humans with preclinical experiments in macaques to answer questions that would otherwise be impossible, and provide avenues for curing human disease. ,” said Maziartz, a professor of medicine. He is Professor of Medicine at the OHSU School of Medicine and Medical Director of the Adult Blood and Bone Marrow Stem Cell Transplant and Cell Therapy Program at the OHSU Knight Cancer Institute.

of how behind the treatment

Sasha said he was happy to see stem cell transplants cure non-human primates, but said he and his fellow scientists wanted to understand. how done. When evaluating samples taken from human subjects, scientists discovered two ways to beat HIV.

First, the transplanted donor stem cells helped kill the recipient’s HIV-infected cells by recognizing them as foreign invaders and attacking them. This is similar to the graft-versus-leukemia process that cures cancer in people.

Second, in the two subjects who did not heal, the virus was able to enter the transplanted donor cells. Subsequent experiments confirmed that HIV can infect donor cells while they are attacking HIV. This has led the researchers to decide that it is important to stop HIV use. CCR5 Healing also requires receptors to infect donor cells.

Researchers also found that HIV is cleared from the subject’s body in a series of steps. First, scientists confirmed that HIV was no longer detected in the blood circulating in the arms and legs. Second, they couldn’t find HIV in the lymph nodes, the clumps of immune tissue that contain white blood cells and fight infection. HIV infection was first detected in extremity lymph nodes, followed by abdominal lymph nodes.

The step-wise manner in which scientists have observed HIV elimination may help doctors evaluate the effectiveness of potential HIV treatments. For example, clinicians can focus on analyzing blood collected from both peripheral veins and lymph nodes. This knowledge may also help explain why some transplant recipients initially appeared cured but were later found to have HIV. Sascha hypothesizes that these patients may have small reservoirs of HIV in their abdominal lymph nodes, allowing the virus to persist and spread again throughout the body.

Sasha and colleagues continue to study two non-human primates who have been cured of HIV. We will then investigate the immune response in greater depth, including identifying all the specific immune cells involved and identifying which specific cells or molecules were targeted by the immune system.

This work was supported by the National Institutes of Health (grant AI112433, AI129703, P51 OD011092), the AIDS Research Foundation (grant 108832), and the AIDS Immunity Research Foundation. The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

To ensure the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages any relationships our researchers may have with bodies outside OHSU. I’m here. Regarding this research, Dr. Sacha has a significant financial interest in his CytoDyn company, which may have commercial interest in the research results and OHSU Conflict of Interest Program Details Learn more about how we manage these business relationships.

All research involving animals at OHSU is subject to university review and approval. Institutional Animal Care and Use Committee (IACUC). The priority of IACUC is to ensure the health and safety of animal research subjects. The IACUC will also review procedures to ensure the health and safety of those who work with animals. OHSU cannot work on live animals without IACUC approval.

References: Helen Wu, Kathleen Bassman-Sahaye, Whitney C. Webber, Courtney M. Weitashek, Carla D. Boyle, Katherine Bateman, Jason S. Reed, Joseph M. Huang, Christine Schreiber-Mansch, Tonya Swanson, Mina Northrup, Kimberly Ermantraut, Heidi Price, Mitch Robertson-Lubey, Samantha Atke, Misra R. Kumar, Emily J. Frey, Sol Taylor-Brill, Stephen Bondok, Rebecca Agner, Stephanie L. Junell, Alfred W. Legaz, Cassandra Moates, Rachel M. Borchert, Joseph Shulba, Benjamin N. Bimber, Michelle N. Sullivan, Brandi Dozier, Rhonda P. McAllister, Theodore R. Hobbs , Lauren D. Martin, Angela Panoscalzis Mortari, Lois MA Colgin, Robert F. Silciano, Janet D. Silciano, Jacob D. Estes, Jeremy V. Smedly, Michael K. Axthelm, Gabrielle Meyers, Richard T. Maziarz, Benjamin J. Burwitz, Jeffrey J. Stanton, Jonah B. Sacha, Clearing latent virus after allogeneic stem cell transplantation by alloimmunization Immunization in SIV-infected antiretroviral therapy-suppressed macaque monkeys, 25 May 2023, DOI : 10.1016/j.immuni.2023.04.019.




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