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Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study
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نویسنده
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cummins n.w. ,rizza s. ,litzow m.r. ,hua s. ,lee g.q. ,einkauf k. ,chun t.-w. ,rhame f. ,baker j.v. ,busch m.p. ,chomont n. ,dean p.g. ,fromentin r. ,haase a.t. ,hampton d. ,keating s.m. ,lada s.m. ,lee t.-h. ,natesampillai s. ,richman d.d. ,schacker t.w. ,wietgrefe s. ,yu x.g. ,yao j.d. ,zeuli j. ,lichterfeld m. ,badley a.d.
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منبع
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plos medicine - 2017 - دوره : 14 - شماره : 11
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چکیده
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Background: notwithstanding 1 documented case of hiv-1 cure following allogeneic stem cell transplantation (allo-sct),several subsequent cases of allo-sct in hiv-1 positive individuals have failed to cure hiv-1 infection. the aim of our study was to describe changes in the hiv reservoir in a single chronically hiv-infected patient on suppressive antiretroviral therapy who underwent allo-sct for treatment of acute lymphoblastic leukemia. methods and findings: we prospectively collected peripheral blood mononuclear cells (pbmcs) by leukapheresis from a 55-year-old man with chronic hiv infection before and after allo-sct to measure the size of the hiv-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. at day 784 post-transplant,when hiv-1 was undetectable by multiple measures—including pcr measurements of both total and integrated hiv-1 dna,replication-competent virus measurement by large cell input quantitative viral outgrowth assay,and in situ hybridization of colon tissue—the patient consented to an analytic treatment interruption (ati) with frequent clinical monitoring. he remained aviremic off antiretroviral therapy until ati day 288,when a low-level virus rebound of 60 hiv-1 copies/ml occurred,which increased to 1,640 hiv-1 copies/ml 5 days later,prompting reinitiation of art. rebounding plasma hiv-1 sequences were phylogenetically distinct from proviral hiv-1 dna detected in circulating pbmcs before transplantation. the main limitations of this study are the insensitivity of reservoir measurements,and the fact that it describes a single case. conclusions: allo-sct led to a significant reduction in the size of the hiv-1 reservoir and a >9-month-long art-free remission from hiv-1 replication. phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the pbmcs. © 2017 public library of science. all rights reserved.
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آدرس
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division of infectious diseases,mayo clinic,rochester,mn, United States, division of infectious diseases,mayo clinic,rochester,mn, United States, division of hematology,mayo clinic,rochester,mn, United States, ragon institute of mgh,mit and harvard,cambridge,ma, United States, ragon institute of mgh,mit and harvard,cambridge,ma, United States, ragon institute of mgh,mit and harvard,cambridge,ma, United States, hiv immunovirology unit,laboratory of immunoregulation,national institute of allergy and infectious diseases,national institutes of health,bethesda,md, United States, abbott northwestern hospital,allina health,minneapolis,mn,united states,department of microbiology and immunology,university of minnesota,minneapolis,mn, United States, division of infectious diseases,hennepin county medical center,minneapolis,mn, United States, blood systems research institute,san francisco,ca,united states,department of laboratory medicine,university of california,san francisco,san francisco,ca, United States, centre de recherche du chum,university of montreal hospital centre,montreal,canada,department of microbiology,infectious diseases and immunology,university of montreal,montreal, Canada, division of transplantation surgery,mayo clinic,rochester,mn, United States, centre de recherche du chum,university of montreal hospital centre,montreal,canada,department of microbiology,infectious diseases and immunology,university of montreal,montreal, Canada, department of microbiology and immunology,university of minnesota,minneapolis,mn, United States, blood systems research institute,san francisco,ca, United States, blood systems research institute,san francisco,ca,united states,department of laboratory medicine,university of california,san francisco,san francisco,ca, United States, university of california,san diego,san diego,ca,united states,va san diego healthcare system,san diego,ca, United States, blood systems research institute,san francisco,ca, United States, division of infectious diseases,mayo clinic,rochester,mn, United States, university of california,san diego,san diego,ca,united states,va san diego healthcare system,san diego,ca, United States, department of medicine,university of minnesota,minneapolis,mn, United States, department of microbiology and immunology,university of minnesota,minneapolis,mn, United States, ragon institute of mgh,mit and harvard,cambridge,ma,united states,infectious disease division,brigham and women’s hospital,boston,ma, United States, department of laboratory medicine and pathology,mayo clinic,rochester,mn, United States, division of infectious diseases,mayo clinic,rochester,mn, United States, ragon institute of mgh,mit and harvard,cambridge,ma,united states,infectious disease division,brigham and women’s hospital,boston,ma, United States, division of infectious diseases,mayo clinic,rochester,mn, United States
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Authors
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