MSGID: 1:317/3 64703613   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Research offers clues for potential widespread HIV cure in people    
    New study reveals first details on how stem cell transplantation can kill   
   virus that causes AIDS    
      
     Date:   
         May 25, 2023   
     Source:   
         Oregon Health & Science University   
     Summary:   
         New animal research is helping explain why at least five people   
         have become HIV-free after receiving a stem cell transplant,   
         and may bring scientists closer to developing what they hope will   
         be a widespread cure for the virus that causes AIDS. A new study   
         describes how two nonhuman primates were cured of the monkey form   
         of HIV after receiving a stem cell transplant. It also reveals that   
         two circumstances must co-exist for a cure to occur and documents   
         the order in which HIV is cleared from the body.   
      
      
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   FULL STORY   
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   New research from Oregon Health & Science University is helping explain   
   why at least five people have become HIV-free after receiving a stem   
   cell transplant.   
      
   The study's insights may bring scientists closer to developing what   
   they hope will become a widespread cure for the virus that causes AIDS,   
   which has infected about 38 million people worldwide.   
      
   Published today in the journal Immunity, the OHSU-led study describes   
   how two nonhuman primates were cured of the monkey form of HIV after   
   receiving a stem cell transplant. It also reveals that two circumstances   
   must co-exist for a cure to occur and documents the order in which HIV   
   is cleared from the body - - details that can inform efforts to make   
   this cure applicable to more people.   
      
   "Five patients have already demonstrated that HIV can be cured," said the   
   study's lead researcher, Jonah Sacha, Ph.D., a professor at OHSU's Oregon   
   National Primate Research Center and Vaccine and Gene Therapy Institute.   
      
   "This study is helping us home in on the mechanisms involved in making   
   that cure happen," Sacha continued. "We hope our discoveries will help to   
   make this cure work for anyone, and ideally through a single injection   
   instead of a stem cell transplant."  The first known case of HIV being   
   cured through a stem cell transplant was reported in 2009. A man who was   
   living with HIV was also diagnosed with acute myeloid leukemia, a type of   
   cancer, and underwent a stem cell transplant in Berlin, Germany. Stem   
   cell transplants, which are also called bone marrow transplants,   
   are used to treat some forms of cancer. Known as the Berlin patient,   
   he received donated stem cells from someone with a mutated CCR5 gene,   
   which normally codes for a receptor on the surface of white blood cells   
   that HIV uses to infect new cells. A CCR5 mutation makes it difficult for   
   the virus to infect cells, and can make people resistant to HIV. Since   
   the Berlin patient, four more people have been similarly cured.   
      
   This study was conducted with a species of nonhuman primate known   
   as Mauritian cynomolgus macaques, which the research team previously   
   demonstrated can successfully receive stem cell transplants. While all of   
   the study's eight subjects had HIV, four of them underwent a transplant   
   with stem cells from HIV- negative donors, and the other half served as   
   the study's controls and went without transplants.   
      
   Of the four that received transplants, two were cured of HIV after   
   successfully being treated for graft-versus-host disease, which is   
   commonly associated with stem cell transplants.   
      
   Other researchers have tried to cure nonhuman primates of HIV using   
   similar methods, but this study marks the first time that HIV-cured   
   research animals have survived long term. Both remain alive and HIV-free   
   today, about four years after transplantation. Sacha attributes their   
   survival to exceptional care from Oregon National Primate Research Center   
   veterinarians and the support of two study coauthors, OHSU clinicians who   
   care for people who undergo stem cell transplants: Richard T. Maziarz,   
   M.D., and Gabrielle Meyers, M.D.   
      
   "These results highlight the power of linking human clinical studies   
   with pre- clinical macaque experiments to answer questions that would be   
   almost impossible to do otherwise, as well as demonstrate a path forward   
   to curing human disease," said Maziarz, a professor of medicine in the   
   OHSU School of Medicine and medical director of the adult blood and   
   marrow stem cell transplant and cellular therapy programs in the OHSU   
   Knight Cancer Institute.   
      
   The how behind the cure Although Sacha said it was gratifying to confirm   
   stem cell transplantation cured the nonhuman primates, he and his fellow   
   scientists also wanted to understand how it worked. While evaluating   
   samples from the subjects, the scientists determined there were two   
   different, but equally important, ways they beat HIV.   
      
   First, the transplanted donor stem cells helped kill the recipients' HIV-   
   infected cells by recognizing them as foreign invaders and attacking   
   them, similar to the process of graft-versus-leukemia that can cure   
   people of cancer.   
      
   Second, in the two subjects that were not cured, the virus managed to jump   
   into the transplanted donor cells. A subsequent experiment verified that   
   HIV was able to infect the donor cells while they were attacking HIV. This   
   led the researchers to determine that stopping HIV from using the CCR5   
   receptor to infect donor cells is also needed for a cure to occur.   
      
   The researchers also discovered that HIV was cleared from the subjects'   
   bodies in a series of steps. First, the scientists saw that HIV was no   
   longer detectable in blood circulating in their arms and legs. Next,   
   they couldn't find HIV in lymph nodes, or lumps of immune tissue that   
   contain white blood cells and fight infection. Lymph nodes in the limbs   
   were the first to be HIV- free, followed by lymph nodes in the abdomen.   
      
   The step-wise fashion by which the scientists observed HIV being cleared   
   could help physicians as they evaluate the effectiveness of potential HIV   
   cures. For example, clinicians could focus on analyzing blood collected   
   from both peripheral veins and lymph nodes. This knowledge may also help   
   explain why some patients who have received transplants initially have   
   appeared to be cured, but HIV was later detected. Sacha hypothesizes that   
   those patients may have had a small reservoir of HIV in their abdominal   
   lymph nodes that enabled the virus to persist and spread again throughout   
   the body.   
      
   Sacha and colleagues continue to study the two nonhuman primates cured   
   of HIV.   
      
   Next, they plan to dig deeper into their immune responses, including   
   identifying all of the specific immune cells involved and which specific   
   cells or molecules were targeted by the immune system.   
      
   This research is supported by the National Institutes of Health (grants   
   AI112433, AI129703, P51 OD011092) and the Foundation for AIDS Research   
   (grant 108832), and the Foundation for AIDS Immune Research. The content   
   is solely the responsibility of the authors and does not necessarily   
   represent the official views of the National Institutes of Health.   
      
   In our interest of ensuring the integrity of our research and as part of   
   our commitment to public transparency, OHSU actively regulates, tracks   
   and manages relationships that our researchers may hold with entities   
   outside of OHSU. In regard to this research, Dr. Sacha has a significant   
   financial interest in CytoDyn, a company that may have a commercial   
   interest in the results of this research and technology. Review?details   
   of OHSU's conflict of interest program?to find out more about how we   
   manage these business relationships.   
      
   All research involving animal subjects at OHSU must be reviewed and   
   approved by the university's?Institutional Animal Care and Use Committee   
   (IACUC). The IACUC's priority is to ensure the health and safety of   
   animal research subjects. The IACUC also reviews procedures to ensure   
   the health and safety of the people who work with the animals. No live   
   animal work may be conducted at OHSU without IACUC approval.   
      
   REFERENCE: Helen Wu, Kathleen Busman-Sahay, Whitney C. Weber, Courtney M.   
      
   Waytashek, Carla D. Boyle, Katherine 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. 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, Allogeneic immunity clears   
   latent virus following allogenic stem cell transplantation in SIV-infected   
   antiretroviral therapy-suppressed macaques, Immunity, May 25, 2023,   
   DOI: 10.1016/j.immuni.2023.04.019.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # HIV_and_AIDS # Stem_Cells # Infectious_Diseases #   
                   Lymphoma   
             o Plants_&_Animals   
                   # Mice # Biotechnology # Biology #   
                   Biotechnology_and_Bioengineering   
       * RELATED_TERMS   
             o AIDS o HIV_test o Stem_cell o Adult_stem_cell o   
             Embryonic_stem_cell o Stem_cell_treatments o Antiretroviral_drug   
             o Somatic_cell_nuclear_transfer   
      
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   Story Source: Materials provided by   
   Oregon_Health_&_Science_University. Original written by Franny   
   White. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. 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, Jonah B. Sacha. Allogeneic immunity clears latent   
         virus following allogeneic stem cell transplantation in   
         SIV-infected ART- suppressed macaques. Immunity, 2023; DOI:   
         10.1016/j.immuni.2023.04.019   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230525141517.htm   
      
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