Researchers from Oregon Health & Science University (OHSU) have made significant progress in understanding how stem cell transplants can effectively treat HIV, bringing us closer to a potential universal cure for AIDS. Their study revealed that two non-human primates were successfully cured of a strain of HIV through stem cell transplantation, uncovering two crucial factors required for a cure. These factors involve the transplanted stem cells attacking HIV-infected cells and preventing the virus from infecting new cells.
The recent research provides valuable insights into the underlying mechanisms of HIV eradication through stem cell transplantation. The findings, published in the journal Immunity, shed light on the successful treatment of two non-human primates with the simian form of HIV using stem cell transplants. Additionally, the study emphasizes the essential conditions necessary for achieving a cure, which can guide efforts to extend this curative strategy to a larger population.
According to Dr. Jonah Sacha, the lead researcher of the study and a professor at OHSU’s Oregon National Primate Research Center and Vaccine and Gene Therapy Institute, five patients have already demonstrated the potential for HIV cure. The study aims to uncover the intricate mechanisms involved in achieving a cure, with the ultimate goal of making it accessible to everyone through a single injection instead of relying on stem cell transplants.
The first documented case of HIV cure through a stem cell transplant occurred in 2009 when a person with both HIV and acute myeloid leukemia underwent a stem cell transplant in Berlin, Germany. This individual, commonly known as the Berlin patient, received stem cells from a donor with a mutated CCR5 gene, which confers resistance to HIV. Since then, four more individuals have been cured using similar methods.
The recent study was conducted on a species of non-human primate called Mauritian cynomolgus macaques, which have previously shown success in receiving stem cell transplants. Out of the eight subjects in the study, four underwent transplants with stem cells from HIV-negative donors, while the remaining four served as the control group without transplants.
Of the four recipients who received transplants, two were cured of HIV after successfully overcoming graft-versus-host disease, a common complication associated with stem cell transplants.
While previous attempts to cure non-human primates of HIV using similar methods were unsuccessful in the long term, this study stands out as the first to achieve long-term survival of HIV-cured research animals. The two subjects remain alive and free of HIV four years after the transplantation procedure. The researchers attribute this success to the exceptional care provided by Oregon National Primate Research Center veterinarians and the support of two study co-authors, Dr. Richard T. Maziarz and Dr. Gabrielle Meyers, who specialize in caring for individuals undergoing stem cell transplants at OHSU.
The Mechanism of the Cure
In addition to confirming the efficacy of stem cell transplantation in curing non-human primates of HIV, the researchers sought to understand the underlying mechanism. By analyzing samples from the subjects, they identified two distinct but equally vital pathways responsible for eliminating HIV.
Firstly, the transplanted donor stem cells recognized the recipients’ HIV-infected cells as foreign invaders and attacked them, akin to the graft-versus-leukemia process that can cure cancer.
Secondly, in the two subjects who were not cured, the virus managed to infect the transplanted donor cells during their attack on HIV. An additional experiment confirmed that HIV could infect the donor cells while they were targeting the virus. This led the researchers to conclude that preventing HIV from using the CCR5 receptor to infect donor cells is also crucial for achieving a cure.
The researchers also observed a step-wise clearance of HIV from the subjects’ bodies. Initially, HIV became undetectable in the blood circulating in their limbs. Subsequently, the virus disappeared from lymph nodes, which are immune tissue containing white blood cells that fight infections. The clearance of HIV occurred first in the lymph nodes of the limbs, followed by those in the abdomen.
This step-wise pattern of HIV clearance could prove beneficial for evaluating the effectiveness of potential HIV cures in clinical settings. Physicians may focus on analyzing blood samples collected from both peripheral veins and lymph nodes. Furthermore, this knowledge might explain why some patients who initially appeared to be cured after receiving transplants later showed detectable levels of HIV. Sacha suggests that these individuals may have had a small reservoir of HIV in their abdominal lymph nodes, allowing the virus to persist and spread throughout the body again.
Continuing their research, Sacha and his colleagues plan to delve deeper into the immune responses of the two non-human primates that were cured of HIV. They aim to identify the specific immune cells involved and determine the targeted cells or molecules within the immune system.
Reference: “Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques” by Helen L. Wu, Kathleen Busman-Sahay, Whitney C. Weber, Courtney M. Waytashek, Carla D. Boyle, Katherine B. Bateman, Jason S. Reed, Joseph M. Hwang, Christine Shriver-Munsch, Tonya Swanson, Mina Northrup, Kimberly Armantrout, Heidi Price, Mitch Robertson-LeVay, Samantha Uttke, Mithra R. Kumar, Emily J. Fray, Sol Taylor-Brill, Stephen Bondoc, Rebecca Agnor, Stephanie L. Junell, Alfred W. Legasse, Cassandra Moats, Rachele M. Bochart, Joseph Sciurba, Benjamin N. Bimber, Michelle N. Sullivan, Brandy Dozier, Rhonda P. MacAllister, Theodore R. Hobbs, Lauren D. Martin, Angela Panoskaltsis-Mortari, Lois M.A. Colgin, Robert F. Siliciano, Janet D. Siliciano, Jacob D. Estes, Jeremy V. Smedley, Michael K. Axthelm, Gabrielle Meyers, Richard T. Maziarz, Benjamin J. Burwitz, Jeffrey J. Stanton, and Jonah B. Sacha, 25 May 2023, Immunity.
The study received funding from the National Institutes of Health, the Foundation for AIDS Research, and the Foundation for AIDS Immune Research.
Frequently Asked Questions (FAQs) about HIV cure
What is the significance of the recent research on HIV and stem cell transplants?
The recent research on HIV and stem cell transplants is significant because it sheds light on the potential for a universal cure for AIDS. It demonstrates that stem cell transplants can effectively eliminate HIV in non-human primates, bringing us closer to developing a widespread remedy for the virus that affects millions of people worldwide.
How were the non-human primates cured of HIV in the study?
The non-human primates in the study were cured of HIV through stem cell transplantation. The transplanted donor stem cells attacked the HIV-infected cells and prevented the virus from infecting new cells. Additionally, the study revealed that stopping HIV from using the CCR5 receptor to infect donor cells is essential for a cure to occur.
What is the step-wise clearance of HIV observed in the study?
The study observed a step-wise clearance of HIV from the subjects’ bodies. First, the virus became undetectable in the blood circulating in their limbs. Next, HIV disappeared from lymph nodes, starting with those in the limbs and then in the abdomen. This step-wise pattern provides insights into evaluating the effectiveness of potential HIV cures and may explain cases where HIV reemerges after apparent initial clearance.
How does this research contribute to finding a cure for HIV in humans?
This research provides valuable insights into the mechanisms involved in curing HIV through stem cell transplants. By understanding the immune responses and specific cells involved in the process, researchers can guide efforts to extend this curative strategy to a larger population. The findings offer hope and a pathway towards developing a potential universal cure for HIV in humans.
Are there any implications for future medical treatments?
Yes, the findings have significant implications for future medical treatments. The study suggests the possibility of developing a universal cure for HIV that can be administered through a single injection, eliminating the need for stem cell transplants. The step-wise clearance of HIV observed in the study may also aid physicians in evaluating the effectiveness of potential HIV cures and understanding the persistence of the virus in certain cases.
More about HIV cure
- Oregon Health & Science University (OHSU)
- Journal Immunity
- National Institutes of Health (NIH)
- Foundation for AIDS Research
- Foundation for AIDS Immune Research
- Oregon National Primate Research Center