HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo.
We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-pr...
Ausführliche Beschreibung
Autor*in: |
Charlotte V Hobbs [verfasserIn] Jillian Neal [verfasserIn] Solomon Conteh [verfasserIn] Liam Donnelly [verfasserIn] Jingyang Chen [verfasserIn] Kennan Marsh [verfasserIn] Lynn Lambert [verfasserIn] Sachy Orr-Gonzalez [verfasserIn] Jessica Hinderer [verfasserIn] Sara Healy [verfasserIn] William Borkowsky [verfasserIn] Scott R Penzak [verfasserIn] Sumana Chakravarty [verfasserIn] Stephen L Hoffman [verfasserIn] Patrick E Duffy [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2014 |
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Übergeordnetes Werk: |
In: PLoS ONE - Public Library of Science (PLoS), 2007, 9(2014), 7, p e100138 |
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Übergeordnetes Werk: |
volume:9 ; year:2014 ; number:7, p e100138 |
Links: |
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DOI / URN: |
10.1371/journal.pone.0100138 |
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Katalog-ID: |
DOAJ011046627 |
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10.1371/journal.pone.0100138 doi (DE-627)DOAJ011046627 (DE-599)DOAJ353182e7d7cc4458a8f133409bc2339a DE-627 ger DE-627 rakwb eng Charlotte V Hobbs verfasserin aut HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo. 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Medicine R Science Q Jillian Neal verfasserin aut Solomon Conteh verfasserin aut Liam Donnelly verfasserin aut Jingyang Chen verfasserin aut Kennan Marsh verfasserin aut Lynn Lambert verfasserin aut Sachy Orr-Gonzalez verfasserin aut Jessica Hinderer verfasserin aut Sara Healy verfasserin aut William Borkowsky verfasserin aut Scott R Penzak verfasserin aut Sumana Chakravarty verfasserin aut Stephen L Hoffman verfasserin aut Patrick E Duffy verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 9(2014), 7, p e100138 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:9 year:2014 number:7, p e100138 https://doi.org/10.1371/journal.pone.0100138 kostenfrei https://doaj.org/article/353182e7d7cc4458a8f133409bc2339a kostenfrei http://europepmc.org/articles/PMC4079689?pdf=render kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2014 7, p e100138 |
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10.1371/journal.pone.0100138 doi (DE-627)DOAJ011046627 (DE-599)DOAJ353182e7d7cc4458a8f133409bc2339a DE-627 ger DE-627 rakwb eng Charlotte V Hobbs verfasserin aut HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo. 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Medicine R Science Q Jillian Neal verfasserin aut Solomon Conteh verfasserin aut Liam Donnelly verfasserin aut Jingyang Chen verfasserin aut Kennan Marsh verfasserin aut Lynn Lambert verfasserin aut Sachy Orr-Gonzalez verfasserin aut Jessica Hinderer verfasserin aut Sara Healy verfasserin aut William Borkowsky verfasserin aut Scott R Penzak verfasserin aut Sumana Chakravarty verfasserin aut Stephen L Hoffman verfasserin aut Patrick E Duffy verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 9(2014), 7, p e100138 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:9 year:2014 number:7, p e100138 https://doi.org/10.1371/journal.pone.0100138 kostenfrei https://doaj.org/article/353182e7d7cc4458a8f133409bc2339a kostenfrei http://europepmc.org/articles/PMC4079689?pdf=render kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2014 7, p e100138 |
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10.1371/journal.pone.0100138 doi (DE-627)DOAJ011046627 (DE-599)DOAJ353182e7d7cc4458a8f133409bc2339a DE-627 ger DE-627 rakwb eng Charlotte V Hobbs verfasserin aut HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo. 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Medicine R Science Q Jillian Neal verfasserin aut Solomon Conteh verfasserin aut Liam Donnelly verfasserin aut Jingyang Chen verfasserin aut Kennan Marsh verfasserin aut Lynn Lambert verfasserin aut Sachy Orr-Gonzalez verfasserin aut Jessica Hinderer verfasserin aut Sara Healy verfasserin aut William Borkowsky verfasserin aut Scott R Penzak verfasserin aut Sumana Chakravarty verfasserin aut Stephen L Hoffman verfasserin aut Patrick E Duffy verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 9(2014), 7, p e100138 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:9 year:2014 number:7, p e100138 https://doi.org/10.1371/journal.pone.0100138 kostenfrei https://doaj.org/article/353182e7d7cc4458a8f133409bc2339a kostenfrei http://europepmc.org/articles/PMC4079689?pdf=render kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2014 7, p e100138 |
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10.1371/journal.pone.0100138 doi (DE-627)DOAJ011046627 (DE-599)DOAJ353182e7d7cc4458a8f133409bc2339a DE-627 ger DE-627 rakwb eng Charlotte V Hobbs verfasserin aut HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo. 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Medicine R Science Q Jillian Neal verfasserin aut Solomon Conteh verfasserin aut Liam Donnelly verfasserin aut Jingyang Chen verfasserin aut Kennan Marsh verfasserin aut Lynn Lambert verfasserin aut Sachy Orr-Gonzalez verfasserin aut Jessica Hinderer verfasserin aut Sara Healy verfasserin aut William Borkowsky verfasserin aut Scott R Penzak verfasserin aut Sumana Chakravarty verfasserin aut Stephen L Hoffman verfasserin aut Patrick E Duffy verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 9(2014), 7, p e100138 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:9 year:2014 number:7, p e100138 https://doi.org/10.1371/journal.pone.0100138 kostenfrei https://doaj.org/article/353182e7d7cc4458a8f133409bc2339a kostenfrei http://europepmc.org/articles/PMC4079689?pdf=render kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2014 7, p e100138 |
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10.1371/journal.pone.0100138 doi (DE-627)DOAJ011046627 (DE-599)DOAJ353182e7d7cc4458a8f133409bc2339a DE-627 ger DE-627 rakwb eng Charlotte V Hobbs verfasserin aut HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo. 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Medicine R Science Q Jillian Neal verfasserin aut Solomon Conteh verfasserin aut Liam Donnelly verfasserin aut Jingyang Chen verfasserin aut Kennan Marsh verfasserin aut Lynn Lambert verfasserin aut Sachy Orr-Gonzalez verfasserin aut Jessica Hinderer verfasserin aut Sara Healy verfasserin aut William Borkowsky verfasserin aut Scott R Penzak verfasserin aut Sumana Chakravarty verfasserin aut Stephen L Hoffman verfasserin aut Patrick E Duffy verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 9(2014), 7, p e100138 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:9 year:2014 number:7, p e100138 https://doi.org/10.1371/journal.pone.0100138 kostenfrei https://doaj.org/article/353182e7d7cc4458a8f133409bc2339a kostenfrei http://europepmc.org/articles/PMC4079689?pdf=render kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2014 7, p e100138 |
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HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo |
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HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo. |
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HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo |
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Charlotte V Hobbs |
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Charlotte V Hobbs Jillian Neal Solomon Conteh Liam Donnelly Jingyang Chen Kennan Marsh Lynn Lambert Sachy Orr-Gonzalez Jessica Hinderer Sara Healy William Borkowsky Scott R Penzak Sumana Chakravarty Stephen L Hoffman Patrick E Duffy |
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hiv treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo |
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HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo. |
abstract |
We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. |
abstractGer |
We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. |
abstract_unstemmed |
We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. |
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HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo. |
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