Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study.
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...
Ausführliche Beschreibung
Autor*in: |
Nathan W Cummins [verfasserIn] Stacey Rizza [verfasserIn] Mark R Litzow [verfasserIn] Stephane Hua [verfasserIn] Guinevere Q Lee [verfasserIn] Kevin Einkauf [verfasserIn] Tae-Wook Chun [verfasserIn] Frank Rhame [verfasserIn] Jason V Baker [verfasserIn] Michael P Busch [verfasserIn] Nicolas Chomont [verfasserIn] Patrick G Dean [verfasserIn] Rémi Fromentin [verfasserIn] Ashley T Haase [verfasserIn] Dylan Hampton [verfasserIn] Sheila M Keating [verfasserIn] Steven M Lada [verfasserIn] Tzong-Hae Lee [verfasserIn] Sekar Natesampillai [verfasserIn] Douglas D Richman [verfasserIn] Timothy W Schacker [verfasserIn] Stephen Wietgrefe [verfasserIn] Xu G Yu [verfasserIn] Joseph D Yao [verfasserIn] John Zeuli [verfasserIn] Mathias Lichterfeld [verfasserIn] Andrew D Badley [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2017 |
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Übergeordnetes Werk: |
In: PLoS Medicine - Public Library of Science (PLoS), 2004, 14(2017), 11, p e1002461 |
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Übergeordnetes Werk: |
volume:14 ; year:2017 ; number:11, p e1002461 |
Links: |
Link aufrufen |
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DOI / URN: |
10.1371/journal.pmed.1002461 |
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Katalog-ID: |
DOAJ073615285 |
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245 | 1 | 0 | |a 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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520 | |a 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. | ||
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700 | 0 | |a Mark R Litzow |e verfasserin |4 aut | |
700 | 0 | |a Stephane Hua |e verfasserin |4 aut | |
700 | 0 | |a Guinevere Q Lee |e verfasserin |4 aut | |
700 | 0 | |a Kevin Einkauf |e verfasserin |4 aut | |
700 | 0 | |a Tae-Wook Chun |e verfasserin |4 aut | |
700 | 0 | |a Frank Rhame |e verfasserin |4 aut | |
700 | 0 | |a Jason V Baker |e verfasserin |4 aut | |
700 | 0 | |a Michael P Busch |e verfasserin |4 aut | |
700 | 0 | |a Nicolas Chomont |e verfasserin |4 aut | |
700 | 0 | |a Patrick G Dean |e verfasserin |4 aut | |
700 | 0 | |a Rémi Fromentin |e verfasserin |4 aut | |
700 | 0 | |a Ashley T Haase |e verfasserin |4 aut | |
700 | 0 | |a Dylan Hampton |e verfasserin |4 aut | |
700 | 0 | |a Sheila M Keating |e verfasserin |4 aut | |
700 | 0 | |a Steven M Lada |e verfasserin |4 aut | |
700 | 0 | |a Tzong-Hae Lee |e verfasserin |4 aut | |
700 | 0 | |a Sekar Natesampillai |e verfasserin |4 aut | |
700 | 0 | |a Douglas D Richman |e verfasserin |4 aut | |
700 | 0 | |a Timothy W Schacker |e verfasserin |4 aut | |
700 | 0 | |a Stephen Wietgrefe |e verfasserin |4 aut | |
700 | 0 | |a Xu G Yu |e verfasserin |4 aut | |
700 | 0 | |a Joseph D Yao |e verfasserin |4 aut | |
700 | 0 | |a John Zeuli |e verfasserin |4 aut | |
700 | 0 | |a Mathias Lichterfeld |e verfasserin |4 aut | |
700 | 0 | |a Andrew D Badley |e verfasserin |4 aut | |
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10.1371/journal.pmed.1002461 doi (DE-627)DOAJ073615285 (DE-599)DOAJ6cb0f7ce4309430794213dddfb5bf122 DE-627 ger DE-627 rakwb eng Nathan W Cummins verfasserin aut Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study. 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Stacey Rizza verfasserin aut Mark R Litzow verfasserin aut Stephane Hua verfasserin aut Guinevere Q Lee verfasserin aut Kevin Einkauf verfasserin aut Tae-Wook Chun verfasserin aut Frank Rhame verfasserin aut Jason V Baker verfasserin aut Michael P Busch verfasserin aut Nicolas Chomont verfasserin aut Patrick G Dean verfasserin aut Rémi Fromentin verfasserin aut Ashley T Haase verfasserin aut Dylan Hampton verfasserin aut Sheila M Keating verfasserin aut Steven M Lada verfasserin aut Tzong-Hae Lee verfasserin aut Sekar Natesampillai verfasserin aut Douglas D Richman verfasserin aut Timothy W Schacker verfasserin aut Stephen Wietgrefe verfasserin aut Xu G Yu verfasserin aut Joseph D Yao verfasserin aut John Zeuli verfasserin aut Mathias Lichterfeld verfasserin aut Andrew D Badley verfasserin aut In PLoS Medicine Public Library of Science (PLoS), 2004 14(2017), 11, p e1002461 (DE-627)470151471 (DE-600)2164823-2 15491676 nnns volume:14 year:2017 number:11, p e1002461 https://doi.org/10.1371/journal.pmed.1002461 kostenfrei https://doaj.org/article/6cb0f7ce4309430794213dddfb5bf122 kostenfrei http://europepmc.org/articles/PMC5705162?pdf=render kostenfrei https://doaj.org/toc/1549-1277 Journal toc kostenfrei https://doaj.org/toc/1549-1676 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 11, p e1002461 |
spelling |
10.1371/journal.pmed.1002461 doi (DE-627)DOAJ073615285 (DE-599)DOAJ6cb0f7ce4309430794213dddfb5bf122 DE-627 ger DE-627 rakwb eng Nathan W Cummins verfasserin aut Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study. 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Stacey Rizza verfasserin aut Mark R Litzow verfasserin aut Stephane Hua verfasserin aut Guinevere Q Lee verfasserin aut Kevin Einkauf verfasserin aut Tae-Wook Chun verfasserin aut Frank Rhame verfasserin aut Jason V Baker verfasserin aut Michael P Busch verfasserin aut Nicolas Chomont verfasserin aut Patrick G Dean verfasserin aut Rémi Fromentin verfasserin aut Ashley T Haase verfasserin aut Dylan Hampton verfasserin aut Sheila M Keating verfasserin aut Steven M Lada verfasserin aut Tzong-Hae Lee verfasserin aut Sekar Natesampillai verfasserin aut Douglas D Richman verfasserin aut Timothy W Schacker verfasserin aut Stephen Wietgrefe verfasserin aut Xu G Yu verfasserin aut Joseph D Yao verfasserin aut John Zeuli verfasserin aut Mathias Lichterfeld verfasserin aut Andrew D Badley verfasserin aut In PLoS Medicine Public Library of Science (PLoS), 2004 14(2017), 11, p e1002461 (DE-627)470151471 (DE-600)2164823-2 15491676 nnns volume:14 year:2017 number:11, p e1002461 https://doi.org/10.1371/journal.pmed.1002461 kostenfrei https://doaj.org/article/6cb0f7ce4309430794213dddfb5bf122 kostenfrei http://europepmc.org/articles/PMC5705162?pdf=render kostenfrei https://doaj.org/toc/1549-1277 Journal toc kostenfrei https://doaj.org/toc/1549-1676 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 11, p e1002461 |
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10.1371/journal.pmed.1002461 doi (DE-627)DOAJ073615285 (DE-599)DOAJ6cb0f7ce4309430794213dddfb5bf122 DE-627 ger DE-627 rakwb eng Nathan W Cummins verfasserin aut Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study. 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Stacey Rizza verfasserin aut Mark R Litzow verfasserin aut Stephane Hua verfasserin aut Guinevere Q Lee verfasserin aut Kevin Einkauf verfasserin aut Tae-Wook Chun verfasserin aut Frank Rhame verfasserin aut Jason V Baker verfasserin aut Michael P Busch verfasserin aut Nicolas Chomont verfasserin aut Patrick G Dean verfasserin aut Rémi Fromentin verfasserin aut Ashley T Haase verfasserin aut Dylan Hampton verfasserin aut Sheila M Keating verfasserin aut Steven M Lada verfasserin aut Tzong-Hae Lee verfasserin aut Sekar Natesampillai verfasserin aut Douglas D Richman verfasserin aut Timothy W Schacker verfasserin aut Stephen Wietgrefe verfasserin aut Xu G Yu verfasserin aut Joseph D Yao verfasserin aut John Zeuli verfasserin aut Mathias Lichterfeld verfasserin aut Andrew D Badley verfasserin aut In PLoS Medicine Public Library of Science (PLoS), 2004 14(2017), 11, p e1002461 (DE-627)470151471 (DE-600)2164823-2 15491676 nnns volume:14 year:2017 number:11, p e1002461 https://doi.org/10.1371/journal.pmed.1002461 kostenfrei https://doaj.org/article/6cb0f7ce4309430794213dddfb5bf122 kostenfrei http://europepmc.org/articles/PMC5705162?pdf=render kostenfrei https://doaj.org/toc/1549-1277 Journal toc kostenfrei https://doaj.org/toc/1549-1676 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 11, p e1002461 |
allfieldsGer |
10.1371/journal.pmed.1002461 doi (DE-627)DOAJ073615285 (DE-599)DOAJ6cb0f7ce4309430794213dddfb5bf122 DE-627 ger DE-627 rakwb eng Nathan W Cummins verfasserin aut Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study. 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Stacey Rizza verfasserin aut Mark R Litzow verfasserin aut Stephane Hua verfasserin aut Guinevere Q Lee verfasserin aut Kevin Einkauf verfasserin aut Tae-Wook Chun verfasserin aut Frank Rhame verfasserin aut Jason V Baker verfasserin aut Michael P Busch verfasserin aut Nicolas Chomont verfasserin aut Patrick G Dean verfasserin aut Rémi Fromentin verfasserin aut Ashley T Haase verfasserin aut Dylan Hampton verfasserin aut Sheila M Keating verfasserin aut Steven M Lada verfasserin aut Tzong-Hae Lee verfasserin aut Sekar Natesampillai verfasserin aut Douglas D Richman verfasserin aut Timothy W Schacker verfasserin aut Stephen Wietgrefe verfasserin aut Xu G Yu verfasserin aut Joseph D Yao verfasserin aut John Zeuli verfasserin aut Mathias Lichterfeld verfasserin aut Andrew D Badley verfasserin aut In PLoS Medicine Public Library of Science (PLoS), 2004 14(2017), 11, p e1002461 (DE-627)470151471 (DE-600)2164823-2 15491676 nnns volume:14 year:2017 number:11, p e1002461 https://doi.org/10.1371/journal.pmed.1002461 kostenfrei https://doaj.org/article/6cb0f7ce4309430794213dddfb5bf122 kostenfrei http://europepmc.org/articles/PMC5705162?pdf=render kostenfrei https://doaj.org/toc/1549-1277 Journal toc kostenfrei https://doaj.org/toc/1549-1676 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 11, p e1002461 |
allfieldsSound |
10.1371/journal.pmed.1002461 doi (DE-627)DOAJ073615285 (DE-599)DOAJ6cb0f7ce4309430794213dddfb5bf122 DE-627 ger DE-627 rakwb eng Nathan W Cummins verfasserin aut Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study. 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Stacey Rizza verfasserin aut Mark R Litzow verfasserin aut Stephane Hua verfasserin aut Guinevere Q Lee verfasserin aut Kevin Einkauf verfasserin aut Tae-Wook Chun verfasserin aut Frank Rhame verfasserin aut Jason V Baker verfasserin aut Michael P Busch verfasserin aut Nicolas Chomont verfasserin aut Patrick G Dean verfasserin aut Rémi Fromentin verfasserin aut Ashley T Haase verfasserin aut Dylan Hampton verfasserin aut Sheila M Keating verfasserin aut Steven M Lada verfasserin aut Tzong-Hae Lee verfasserin aut Sekar Natesampillai verfasserin aut Douglas D Richman verfasserin aut Timothy W Schacker verfasserin aut Stephen Wietgrefe verfasserin aut Xu G Yu verfasserin aut Joseph D Yao verfasserin aut John Zeuli verfasserin aut Mathias Lichterfeld verfasserin aut Andrew D Badley verfasserin aut In PLoS Medicine Public Library of Science (PLoS), 2004 14(2017), 11, p e1002461 (DE-627)470151471 (DE-600)2164823-2 15491676 nnns volume:14 year:2017 number:11, p e1002461 https://doi.org/10.1371/journal.pmed.1002461 kostenfrei https://doaj.org/article/6cb0f7ce4309430794213dddfb5bf122 kostenfrei http://europepmc.org/articles/PMC5705162?pdf=render kostenfrei https://doaj.org/toc/1549-1277 Journal toc kostenfrei https://doaj.org/toc/1549-1676 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 11, p e1002461 |
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Nathan W Cummins @@aut@@ Stacey Rizza @@aut@@ Mark R Litzow @@aut@@ Stephane Hua @@aut@@ Guinevere Q Lee @@aut@@ Kevin Einkauf @@aut@@ Tae-Wook Chun @@aut@@ Frank Rhame @@aut@@ Jason V Baker @@aut@@ Michael P Busch @@aut@@ Nicolas Chomont @@aut@@ Patrick G Dean @@aut@@ Rémi Fromentin @@aut@@ Ashley T Haase @@aut@@ Dylan Hampton @@aut@@ Sheila M Keating @@aut@@ Steven M Lada @@aut@@ Tzong-Hae Lee @@aut@@ Sekar Natesampillai @@aut@@ Douglas D Richman @@aut@@ Timothy W Schacker @@aut@@ Stephen Wietgrefe @@aut@@ Xu G Yu @@aut@@ Joseph D Yao @@aut@@ John Zeuli @@aut@@ Mathias Lichterfeld @@aut@@ Andrew D Badley @@aut@@ |
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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. 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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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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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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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Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study. |
abstract |
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. |
abstractGer |
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. |
abstract_unstemmed |
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. |
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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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https://doi.org/10.1371/journal.pmed.1002461 https://doaj.org/article/6cb0f7ce4309430794213dddfb5bf122 http://europepmc.org/articles/PMC5705162?pdf=render https://doaj.org/toc/1549-1277 https://doaj.org/toc/1549-1676 |
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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. 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