Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus
GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques we...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2014-03, Vol.343 (6175), p.1151-1154 |
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| creator | Andrews, Chasity D. Spreen, William R. Mohri, Hiroshi Moss, Lee Ford, Susan Gettie, Agegnehu Russell-Lodrigue, Kasi Bohm, Rudolf P. Cheng-Mayer, Cecilia Hong, Zhi Markowitz, Martin Ho, David D. |
| description | GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP). |
| doi_str_mv | 10.1126/science.1248707 |
| format | Article |
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GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP).</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1248707</identifier><identifier>PMID: 24594934</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject><![CDATA[AIDS ; Animals ; Clinical trials ; Delayed-Action Preparations - administration & dosage ; Delayed-Action Preparations - pharmacokinetics ; Dosage ; HIV ; HIV infections ; HIV Infections - prevention & control ; HIV Integrase Inhibitors - administration & dosage ; HIV Integrase Inhibitors - blood ; HIV Integrase Inhibitors - pharmacokinetics ; HIV-1 - drug effects ; Human immunodeficiency virus ; Humans ; Infections ; Inhibitor drugs ; Injections ; Insect ecology ; Macaca mulatta ; Malaria ; Molecular Sequence Data ; Monkeys & apes ; Plasma ; Pyridones - administration & dosage ; Rectum - virology ; Simian Acquired Immunodeficiency Syndrome - prevention & control ; Simian Immunodeficiency Virus - drug effects ; Viruses]]></subject><ispartof>Science (American Association for the Advancement of Science), 2014-03, Vol.343 (6175), p.1151-1154</ispartof><rights>Copyright © 2014 American Association for the Advancement of Science</rights><rights>Copyright © 2014, American Association for the Advancement of Science</rights><rights>Copyright 2014 by the American Association for the Advancement of Science; all rights reserved. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-a8d8ddb97c8c0c9767e657bd57a07fdce5c06ca215169181b8896edd46df7cb23</citedby><cites>FETCH-LOGICAL-c509t-a8d8ddb97c8c0c9767e657bd57a07fdce5c06ca215169181b8896edd46df7cb23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24743332$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24743332$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24594934$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andrews, Chasity D.</creatorcontrib><creatorcontrib>Spreen, William R.</creatorcontrib><creatorcontrib>Mohri, Hiroshi</creatorcontrib><creatorcontrib>Moss, Lee</creatorcontrib><creatorcontrib>Ford, Susan</creatorcontrib><creatorcontrib>Gettie, Agegnehu</creatorcontrib><creatorcontrib>Russell-Lodrigue, Kasi</creatorcontrib><creatorcontrib>Bohm, Rudolf P.</creatorcontrib><creatorcontrib>Cheng-Mayer, Cecilia</creatorcontrib><creatorcontrib>Hong, Zhi</creatorcontrib><creatorcontrib>Markowitz, Martin</creatorcontrib><creatorcontrib>Ho, David D.</creatorcontrib><title>Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP).</description><subject>AIDS</subject><subject>Animals</subject><subject>Clinical trials</subject><subject>Delayed-Action Preparations - administration & dosage</subject><subject>Delayed-Action Preparations - pharmacokinetics</subject><subject>Dosage</subject><subject>HIV</subject><subject>HIV infections</subject><subject>HIV Infections - prevention & control</subject><subject>HIV Integrase Inhibitors - administration & dosage</subject><subject>HIV Integrase Inhibitors - blood</subject><subject>HIV Integrase Inhibitors - pharmacokinetics</subject><subject>HIV-1 - drug effects</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infections</subject><subject>Inhibitor drugs</subject><subject>Injections</subject><subject>Insect ecology</subject><subject>Macaca mulatta</subject><subject>Malaria</subject><subject>Molecular Sequence Data</subject><subject>Monkeys & apes</subject><subject>Plasma</subject><subject>Pyridones - administration & dosage</subject><subject>Rectum - virology</subject><subject>Simian Acquired Immunodeficiency Syndrome - prevention & control</subject><subject>Simian Immunodeficiency Virus - drug 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Immunodeficiency Virus</title><author>Andrews, Chasity D. ; Spreen, William R. ; Mohri, Hiroshi ; Moss, Lee ; Ford, Susan ; Gettie, Agegnehu ; Russell-Lodrigue, Kasi ; Bohm, Rudolf P. ; Cheng-Mayer, Cecilia ; Hong, Zhi ; Markowitz, Martin ; Ho, David D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-a8d8ddb97c8c0c9767e657bd57a07fdce5c06ca215169181b8896edd46df7cb23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>AIDS</topic><topic>Animals</topic><topic>Clinical trials</topic><topic>Delayed-Action Preparations - administration & dosage</topic><topic>Delayed-Action Preparations - pharmacokinetics</topic><topic>Dosage</topic><topic>HIV</topic><topic>HIV infections</topic><topic>HIV Infections - prevention & control</topic><topic>HIV Integrase Inhibitors - administration & dosage</topic><topic>HIV Integrase Inhibitors - blood</topic><topic>HIV Integrase Inhibitors - pharmacokinetics</topic><topic>HIV-1 - drug effects</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Infections</topic><topic>Inhibitor drugs</topic><topic>Injections</topic><topic>Insect ecology</topic><topic>Macaca mulatta</topic><topic>Malaria</topic><topic>Molecular Sequence Data</topic><topic>Monkeys & apes</topic><topic>Plasma</topic><topic>Pyridones - administration & dosage</topic><topic>Rectum - virology</topic><topic>Simian Acquired Immunodeficiency Syndrome - prevention & control</topic><topic>Simian Immunodeficiency Virus - drug effects</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Andrews, Chasity D.</creatorcontrib><creatorcontrib>Spreen, William R.</creatorcontrib><creatorcontrib>Mohri, Hiroshi</creatorcontrib><creatorcontrib>Moss, Lee</creatorcontrib><creatorcontrib>Ford, Susan</creatorcontrib><creatorcontrib>Gettie, 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Andrews, Chasity D.</au><au>Spreen, William R.</au><au>Mohri, Hiroshi</au><au>Moss, Lee</au><au>Ford, Susan</au><au>Gettie, Agegnehu</au><au>Russell-Lodrigue, Kasi</au><au>Bohm, Rudolf P.</au><au>Cheng-Mayer, Cecilia</au><au>Hong, Zhi</au><au>Markowitz, Martin</au><au>Ho, David D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2014-03-07</date><risdate>2014</risdate><volume>343</volume><issue>6175</issue><spage>1151</spage><epage>1154</epage><pages>1151-1154</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP).</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>24594934</pmid><doi>10.1126/science.1248707</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Science (American Association for the Advancement of Science), 2014-03, Vol.343 (6175), p.1151-1154 |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; American Association for the Advancement of Science |
| subjects | AIDS Animals Clinical trials Delayed-Action Preparations - administration & dosage Delayed-Action Preparations - pharmacokinetics Dosage HIV HIV infections HIV Infections - prevention & control HIV Integrase Inhibitors - administration & dosage HIV Integrase Inhibitors - blood HIV Integrase Inhibitors - pharmacokinetics HIV-1 - drug effects Human immunodeficiency virus Humans Infections Inhibitor drugs Injections Insect ecology Macaca mulatta Malaria Molecular Sequence Data Monkeys & apes Plasma Pyridones - administration & dosage Rectum - virology Simian Acquired Immunodeficiency Syndrome - prevention & control Simian Immunodeficiency Virus - drug effects Viruses |
| title | Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus |
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