{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T09:58:51Z","timestamp":1781949531074,"version":"3.54.5"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Fostemsavir, a prodrug of the gp120-directed attachment inhibitor temsavir, is indicated for use in heavily treatment-experienced individuals with MDR HIV-1. Reduced susceptibility to temsavir in the clinic maps to discrete changes at amino acid positions in gp160: S375, M426, M434 and M475.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To query the Los Alamos National Laboratory (LANL) HIV Sequence Database for the prevalence of polymorphisms at gp160 positions of interest.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Full-length gp160 sequences (N\u2009=\u20097560) were queried for amino acid polymorphisms relative to the subtype B consensus at positions of interest; frequencies were reported for all sequences and among subtypes\/circulating recombinant forms (CRFs) with \u226510 isolates in the database.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 239 subtypes in the database, the 5 most prevalent were B (n\u2009=\u20092651, 35.1%), C (n\u2009=\u20091626, 21.5%), CRF01_AE (n\u2009=\u2009674, 8.9%), A1 (n\u2009=\u2009273, 3.6%) and CRF02_AG (n\u2009=\u2009199, 2.6%). Among all 7560 sequences, the most prevalent amino acids at positions of interest (S375, 73.5%; M426, 82.1%; M434, 88.2%; M475, 89.9%) were the same as the subtype B consensus. Specific polymorphisms with the potential to decrease temsavir susceptibility (S375H\/I\/M\/N\/T\/Y, M426L\/P, M434I\/K and M475I) were found in &amp;lt;10% of isolates of subtypes D, G, A6, BC, F1, CRF07_BC, CRF08_BC, 02A, CRF06_cpx, F2, 02G and 02B. S375H and M475I were predominant among CRF01_AE (S375H, 99.3%; M475I, 76.3%; consistent with previously reported low temsavir susceptibility of this CRF) and 01B (S375H, 71.7%; M475I, 49.5%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Analysis of the LANL HIV Sequence Database found a low prevalence of gp160 amino acid polymorphisms with the potential to reduce temsavir susceptibility overall and among most of the common subtypes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab257","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T03:15:33Z","timestamp":1625195733000},"page":"2958-2964","source":"Crossref","is-referenced-by-count":14,"title":["Prevalence of gp160 polymorphisms known to be related to decreased susceptibility to temsavir in different subtypes of HIV-1 in the Los Alamos National Laboratory HIV Sequence Database"],"prefix":"10.1093","volume":"76","author":[{"given":"Margaret","family":"Gartland","sequence":"first","affiliation":[{"name":"ViiV Healthcare, Five Moore Drive, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Arnoult","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T","family":"Foley","sequence":"additional","affiliation":[{"name":"Los Alamos National Laboratory, T-6 Theoretical Biology and Biophysics, Mail Stop K710, Los Alamos, NM 87544, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Lataillade","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ackerman","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Llamoso","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Krystal","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"2021101808540754300_dkab257-B1","year":"2020"},{"key":"2021101808540754300_dkab257-B2","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1056\/NEJMoa1902493","article-title":"Fostemsavir in adults with multidrug-resistant HIV-1 infection","volume":"382","author":"Kozal","year":"2020","journal-title":"N Engl J Med"},{"key":"2021101808540754300_dkab257-B3","doi-asserted-by":"crossref","first-page":"e740\u201351","DOI":"10.1016\/S2352-3018(20)30240-X","article-title":"Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study","volume":"7","author":"Lataillade","year":"2020","journal-title":"Lancet HIV"},{"key":"2021101808540754300_dkab257-B4","doi-asserted-by":"crossref","first-page":"4172","DOI":"10.1128\/AAC.00513-13","article-title":"Activity of the HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068, against CD4-independent viruses and HIV-1 envelopes resistant to other entry inhibitors","volume":"57","author":"Li","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"2021101808540754300_dkab257-B5","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1128\/AAC.00426-12","article-title":"In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068","volume":"56","author":"Nowicka-Sans","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"2021101808540754300_dkab257-B6","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/jac\/dkaa474","article-title":"Susceptibility of global HIV-1 clinical isolates to fostemsavir using the PhenoSense\u00ae Entry assay","volume":"76","author":"Gartland","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"2021101808540754300_dkab257-B7","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1093\/jac\/dkaa178","article-title":"In vitro susceptibility to fostemsavir is not affected by long-term exposure to antiviral therapy in MDR HIV-1-infected patients","volume":"75","author":"Saladini","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2021101808540754300_dkab257-B8","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/QAI.0000000000001602","article-title":"Viral drug resistance through 48 weeks, in a phase 2b, randomized, controlled trial of the HIV-1 attachment inhibitor prodrug, fostemsavir","volume":"77","author":"Lataillade","year":"2018","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2021101808540754300_dkab257-B9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/QAI.0b013e31829726f3","article-title":"Prediction of virological response and assessment of resistance emergence to the HIV-1 attachment inhibitor BMS-626529 during 8-day monotherapy with its prodrug BMS-663068","volume":"64","author":"Ray","year":"2013","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2021101808540754300_dkab257-B10","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/jac\/dkt412","article-title":"Genotypic correlates of susceptibility to HIV-1 attachment inhibitor BMS-626529, the active agent of the prodrug BMS-663068","volume":"69","author":"Zhou","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2021101808540754300_dkab257-B11","article-title":"Clinical significance of gp120 polymorphisms, TMR IC50 FC, and HIV-1 subtype in BRIGHTE","author":"Gartland","year":"2020","journal-title":"Conference on Retroviruses and Opportunistic Infections, Boston, MA, USA"},{"key":"2021101808540754300_dkab257-B12","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1093\/jac\/dkaa034","article-title":"Gp120 substitutions at positions associated with resistance to fostemsavir in treatment-naive HIV-1-positive individuals","volume":"75","author":"Lepore","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2021101808540754300_dkab257-B13","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1093\/jac\/dkt018","article-title":"Frequency of amino acid changes associated with resistance to attachment inhibitor BMS-626529 in R5- and X4-tropic HIV-1 subtype B","volume":"68","author":"Souli\u00e9","year":"2013","journal-title":"J Antimicrob Chemother"},{"key":"2021101808540754300_dkab257-B14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/jac\/dku360","article-title":"Genetic barrier for attachment inhibitor BMS-626529 resistance in HIV-1 B and non-B subtypes","volume":"70","author":"Fofana","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"2021101808540754300_dkab257-B15","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1093\/jac\/dkaa073","article-title":"Identification of gp120 polymorphisms in HIV-1 B subtype potentially associated with resistance to fostemsavir","volume":"75","author":"Bouba","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2021101808540754300_dkab257-B16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1473-3099(18)30647-9","article-title":"Global and regional molecular epidemiology of HIV-1, 1990-2015: a systematic review, global survey, and trend analysis","volume":"19","author":"Hemelaar","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2021101808540754300_dkab257-B17","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/COH.0000000000000534","article-title":"HIV subtype diversity worldwide","volume":"14","author":"Bbosa","year":"2019","journal-title":"Curr Opin HIV AIDS"},{"key":"2021101808540754300_dkab257-B18","doi-asserted-by":"crossref","first-page":"e0170601","DOI":"10.1371\/journal.pone.0170601","article-title":"A national study of the molecular epidemiology of HIV-1 in Australia 2005-2012","volume":"12","author":"Castley","year":"2017","journal-title":"PLoS One"},{"key":"2021101808540754300_dkab257-B19","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1093\/infdis\/jis432","article-title":"Pharmacodynamics, safety, and pharmacokinetics of BMS-663068, an oral HIV-1 attachment inhibitor in HIV-1-infected subjects","volume":"206","author":"Nettles","year":"2012","journal-title":"J Infect Dis"},{"key":"2021101808540754300_dkab257-B20","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1093\/jac\/dky271","article-title":"Impact of natural polymorphisms of HIV-1 non-group M on genotypic susceptibility to the attachment inhibitor fostemsavir","volume":"73","author":"Alessandri-Gradt","year":"2018","journal-title":"J Antimicrob Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/11\/2958\/40641330\/dkab257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/11\/2958\/40641330\/dkab257.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T20:20:28Z","timestamp":1634761228000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/76\/11\/2958\/6327066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,23]]},"references-count":20,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,7,23]]},"published-print":{"date-parts":[[2021,10,11]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkab257","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,1]]},"published":{"date-parts":[[2021,7,23]]}}}