Targeted cytotoxic therapy kills persisting HIV infected cells during ART.

Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA...
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Autor*in:	Paul W Denton [verfasserIn] Julie M Long [verfasserIn] Stephen W Wietgrefe [verfasserIn] Craig Sykes [verfasserIn] Rae Ann Spagnuolo [verfasserIn] Olivia D Snyder [verfasserIn] Katherine Perkey [verfasserIn] Nancie M Archin [verfasserIn] Shailesh K Choudhary [verfasserIn] Kuo Yang [verfasserIn] Michael G Hudgens [verfasserIn] Ira Pastan [verfasserIn] Ashley T Haase [verfasserIn] Angela D Kashuba [verfasserIn] Edward A Berger [verfasserIn] David M Margolis [verfasserIn] J Victor Garcia [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2014

Übergeordnetes Werk:	In: PLoS Pathogens - Public Library of Science (PLoS), 2005, 10(2014), 1, p e1003872
Übergeordnetes Werk:	volume:10 ; year:2014 ; number:1, p e1003872

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1371/journal.ppat.1003872

Katalog-ID:	DOAJ073571660

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520			\|a Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies.
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allfields	10.1371/journal.ppat.1003872 doi (DE-627)DOAJ073571660 (DE-599)DOAJb0f7c03fdd304391a0a5799a98531508 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Paul W Denton verfasserin aut Targeted cytotoxic therapy kills persisting HIV infected cells during ART. 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies. Immunologic diseases. Allergy Biology (General) Julie M Long verfasserin aut Stephen W Wietgrefe verfasserin aut Craig Sykes verfasserin aut Rae Ann Spagnuolo verfasserin aut Olivia D Snyder verfasserin aut Katherine Perkey verfasserin aut Nancie M Archin verfasserin aut Shailesh K Choudhary verfasserin aut Kuo Yang verfasserin aut Michael G Hudgens verfasserin aut Ira Pastan verfasserin aut Ashley T Haase verfasserin aut Angela D Kashuba verfasserin aut Edward A Berger verfasserin aut David M Margolis verfasserin aut J Victor Garcia verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 10(2014), 1, p e1003872 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:10 year:2014 number:1, p e1003872 https://doi.org/10.1371/journal.ppat.1003872 kostenfrei https://doaj.org/article/b0f7c03fdd304391a0a5799a98531508 kostenfrei http://europepmc.org/articles/PMC3887103?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 10 2014 1, p e1003872
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allfields_unstemmed	10.1371/journal.ppat.1003872 doi (DE-627)DOAJ073571660 (DE-599)DOAJb0f7c03fdd304391a0a5799a98531508 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Paul W Denton verfasserin aut Targeted cytotoxic therapy kills persisting HIV infected cells during ART. 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies. Immunologic diseases. Allergy Biology (General) Julie M Long verfasserin aut Stephen W Wietgrefe verfasserin aut Craig Sykes verfasserin aut Rae Ann Spagnuolo verfasserin aut Olivia D Snyder verfasserin aut Katherine Perkey verfasserin aut Nancie M Archin verfasserin aut Shailesh K Choudhary verfasserin aut Kuo Yang verfasserin aut Michael G Hudgens verfasserin aut Ira Pastan verfasserin aut Ashley T Haase verfasserin aut Angela D Kashuba verfasserin aut Edward A Berger verfasserin aut David M Margolis verfasserin aut J Victor Garcia verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 10(2014), 1, p e1003872 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:10 year:2014 number:1, p e1003872 https://doi.org/10.1371/journal.ppat.1003872 kostenfrei https://doaj.org/article/b0f7c03fdd304391a0a5799a98531508 kostenfrei http://europepmc.org/articles/PMC3887103?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 10 2014 1, p e1003872
allfieldsGer	10.1371/journal.ppat.1003872 doi (DE-627)DOAJ073571660 (DE-599)DOAJb0f7c03fdd304391a0a5799a98531508 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Paul W Denton verfasserin aut Targeted cytotoxic therapy kills persisting HIV infected cells during ART. 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies. Immunologic diseases. Allergy Biology (General) Julie M Long verfasserin aut Stephen W Wietgrefe verfasserin aut Craig Sykes verfasserin aut Rae Ann Spagnuolo verfasserin aut Olivia D Snyder verfasserin aut Katherine Perkey verfasserin aut Nancie M Archin verfasserin aut Shailesh K Choudhary verfasserin aut Kuo Yang verfasserin aut Michael G Hudgens verfasserin aut Ira Pastan verfasserin aut Ashley T Haase verfasserin aut Angela D Kashuba verfasserin aut Edward A Berger verfasserin aut David M Margolis verfasserin aut J Victor Garcia verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 10(2014), 1, p e1003872 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:10 year:2014 number:1, p e1003872 https://doi.org/10.1371/journal.ppat.1003872 kostenfrei https://doaj.org/article/b0f7c03fdd304391a0a5799a98531508 kostenfrei http://europepmc.org/articles/PMC3887103?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 10 2014 1, p e1003872
allfieldsSound	10.1371/journal.ppat.1003872 doi (DE-627)DOAJ073571660 (DE-599)DOAJb0f7c03fdd304391a0a5799a98531508 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Paul W Denton verfasserin aut Targeted cytotoxic therapy kills persisting HIV infected cells during ART. 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies. Immunologic diseases. Allergy Biology (General) Julie M Long verfasserin aut Stephen W Wietgrefe verfasserin aut Craig Sykes verfasserin aut Rae Ann Spagnuolo verfasserin aut Olivia D Snyder verfasserin aut Katherine Perkey verfasserin aut Nancie M Archin verfasserin aut Shailesh K Choudhary verfasserin aut Kuo Yang verfasserin aut Michael G Hudgens verfasserin aut Ira Pastan verfasserin aut Ashley T Haase verfasserin aut Angela D Kashuba verfasserin aut Edward A Berger verfasserin aut David M Margolis verfasserin aut J Victor Garcia verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 10(2014), 1, p e1003872 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:10 year:2014 number:1, p e1003872 https://doi.org/10.1371/journal.ppat.1003872 kostenfrei https://doaj.org/article/b0f7c03fdd304391a0a5799a98531508 kostenfrei http://europepmc.org/articles/PMC3887103?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 10 2014 1, p e1003872
language	English
source	In PLoS Pathogens 10(2014), 1, p e1003872 volume:10 year:2014 number:1, p e1003872
sourceStr	In PLoS Pathogens 10(2014), 1, p e1003872 volume:10 year:2014 number:1, p e1003872
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Immunologic diseases. Allergy Biology (General)
isfreeaccess_bool	true
container_title	PLoS Pathogens
authorswithroles_txt_mv	Paul W Denton @@aut@@ Julie M Long @@aut@@ Stephen W Wietgrefe @@aut@@ Craig Sykes @@aut@@ Rae Ann Spagnuolo @@aut@@ Olivia D Snyder @@aut@@ Katherine Perkey @@aut@@ Nancie M Archin @@aut@@ Shailesh K Choudhary @@aut@@ Kuo Yang @@aut@@ Michael G Hudgens @@aut@@ Ira Pastan @@aut@@ Ashley T Haase @@aut@@ Angela D Kashuba @@aut@@ Edward A Berger @@aut@@ David M Margolis @@aut@@ J Victor Garcia @@aut@@
publishDateDaySort_date	2014-01-01T00:00:00Z
hierarchy_top_id	501074422
id	DOAJ073571660
language_de	englisch
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callnumber-first	R - Medicine
author	Paul W Denton
spellingShingle	Paul W Denton misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General) Targeted cytotoxic therapy kills persisting HIV infected cells during ART.
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topic_title	RC581-607 QH301-705.5 Targeted cytotoxic therapy kills persisting HIV infected cells during ART
topic	misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General)
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title	Targeted cytotoxic therapy kills persisting HIV infected cells during ART.
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title_full	Targeted cytotoxic therapy kills persisting HIV infected cells during ART
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author_browse	Paul W Denton Julie M Long Stephen W Wietgrefe Craig Sykes Rae Ann Spagnuolo Olivia D Snyder Katherine Perkey Nancie M Archin Shailesh K Choudhary Kuo Yang Michael G Hudgens Ira Pastan Ashley T Haase Angela D Kashuba Edward A Berger David M Margolis J Victor Garcia
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title_sort	targeted cytotoxic therapy kills persisting hiv infected cells during art
callnumber	RC581-607
title_auth	Targeted cytotoxic therapy kills persisting HIV infected cells during ART.
abstract	Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies.
abstractGer	Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies.
abstract_unstemmed	Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies.
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title_short	Targeted cytotoxic therapy kills persisting HIV infected cells during ART.
url	https://doi.org/10.1371/journal.ppat.1003872 https://doaj.org/article/b0f7c03fdd304391a0a5799a98531508 http://europepmc.org/articles/PMC3887103?pdf=render https://doaj.org/toc/1553-7366 https://doaj.org/toc/1553-7374
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up_date	2024-07-03T18:26:39.059Z
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Targeted cytotoxic therapy kills persisting HIV infected cells during ART.

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