{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:59:08Z","timestamp":1790272748140,"version":"4.1.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T00:00:00Z","timestamp":1584576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Fostemsavir, a novel attachment inhibitor targeting the HIV-1 gp120, has demonstrated wide in vitro activity. However, the high rate of HIV gp120 substitutions could jeopardize its efficacy. We investigated envelope (env) substitutions at positions associated with resistance to fostemsavir in patients with a new HIV-1 diagnosis according to HIV subtype and tropism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Gp120 sequences from 409 subjects were retrospectively analysed and the presence of the L116P, A204D, S375H\/M\/T, M426L, M434I and M475I mutations was evaluated. Other amino acid changes at the same positions were also recorded. The variability at each amino acid position was evaluated using Shannon entropy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The frequency of mutations was: S375T (13.2%); M426L (6.8%); M434I (2.9%); M475I (2.7%); S375H (1.0%)\/M (0.8%) and L116P (0.31%). Statistically significant differences were found at positions 375 (R5\/non-R5 strains and B\/non-B subtypes) and 426 (B\/non-B subtypes); post hoc analysis revealed that significance for position 375 was steered by S375T while for position 426 significance was governed by unusual substitutions, in particular M426R (B\/non-B, P\u2009&amp;lt;\u20090.00001). The variability of env constant domains appeared to be more relevant in the non-B virus population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In conclusion, gp120 substitutions were detected in different subtypes and in both R5 and non-R5 variants. Despite the great variability of gp120, the frequency of mutations was low overall and the predominant substitution was S375T, the role of which in reducing fostemsavir efficacy is less substantial.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa034","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T20:09:21Z","timestamp":1579723761000},"page":"1580-1587","source":"Crossref","is-referenced-by-count":15,"title":["Gp120 substitutions at positions associated with resistance to fostemsavir in treatment-naive HIV-1-positive individuals"],"prefix":"10.1093","volume":"75","author":[{"given":"Luciana","family":"Lepore","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-490X","authenticated-orcid":false,"given":"Claudia","family":"Fabrizio","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy"},{"name":"Malattie Infettive e Tropicali, Ospedale Oncologico San Giuseppe Moscati, Taranto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide Fiore","family":"Bavaro","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Milano","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Volpe","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Lagioia","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioacchino","family":"Angarano","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Saracino","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-4258","authenticated-orcid":false,"given":"Laura","family":"Monno","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,19]]},"reference":[{"key":"2020051504585151100_dkaa034-B1","first-page":"127","article-title":"Investigational antiretroviral drugs: what is coming down the pipeline","volume":"25","author":"Gulick","year":"2018","journal-title":"Topics Antiviral Med"},{"key":"2020051504585151100_dkaa034-B2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1021\/acs.jmedchem.7b01337","article-title":"Inhibitors of HIV-1 attachment: the discovery and development of temsavir and its prodrug fostemsavir","volume":"61","author":"Meanwell","year":"2018","journal-title":"J Med Chem"},{"key":"2020051504585151100_dkaa034-B3","author":"Kozal"},{"key":"2020051504585151100_dkaa034-B4","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":"2020051504585151100_dkaa034-B5","doi-asserted-by":"crossref","first-page":"e427","DOI":"10.1016\/S2352-3018(15)00177-0","article-title":"Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial","volume":"2","author":"Lalezari","year":"2015","journal-title":"Lancet HIV"},{"key":"2020051504585151100_dkaa034-B6","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3851\/IMP3112","article-title":"Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in antiretroviral-experienced subjects: week 48 analysis of AI438011, a phase IIb, randomized controlled trial","volume":"22","author":"Thompson","year":"2017","journal-title":"Antivir Ther"},{"key":"2020051504585151100_dkaa034-B7","first-page":"17","article-title":"Week 48 safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced participants (BRIGHTE study)","volume":"21 Suppl 8","author":"Aberg","year":"2018","journal-title":"JIAS"},{"key":"2020051504585151100_dkaa034-B8","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":"2020051504585151100_dkaa034-B9","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":"2020051504585151100_dkaa034-B10","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":"2020051504585151100_dkaa034-B11","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.1128\/AAC.00743-11","article-title":"Impact of mutations outside the V3 region on coreceptor tropism phenotypically assessed in patients infected with HIV-1 subtype B","volume":"55","author":"Monno","year":"2011","journal-title":"Antimicrob Agents and Chemother"},{"key":"2020051504585151100_dkaa034-B12","doi-asserted-by":"crossref","first-page":"7467","DOI":"10.1128\/JVI.68.11.7467-7481.1994","article-title":"Genetic differences between blood-and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences","volume":"68","author":"Korber","year":"1994","journal-title":"J Virol"},{"key":"2020051504585151100_dkaa034-B13","doi-asserted-by":"crossref","first-page":"e77649","DOI":"10.1371\/journal.pone.0077649","article-title":"Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance","volume":"8","author":"Zheng","year":"2013","journal-title":"PLoS One"},{"key":"2020051504585151100_dkaa034-B14"},{"key":"2020051504585151100_dkaa034-B15","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/COH.0000000000000469","article-title":"Fostemsavir: a new CD4 attachment inhibitor","volume":"13","author":"Cahn","year":"2018","journal-title":"Curr Opin HIV AIDS"},{"key":"2020051504585151100_dkaa034-B16","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2174\/1570162X113116660064","article-title":"HIV-1 variable loop 2 and its importance in HIV-1 infection and vaccine development","volume":"11","author":"Rao","year":"2013","journal-title":"Curr HIV Res"},{"key":"2020051504585151100_dkaa034-B17"},{"key":"2020051504585151100_dkaa034-B18"},{"key":"2020051504585151100_dkaa034-B19","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jcv.2012.08.014","article-title":"An outbreak of HIV-1 BC recombinants in Southern Italy","volume":"55","author":"Monno","year":"2012","journal-title":"J Clin Virol"},{"key":"2020051504585151100_dkaa034-B20","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1128\/AAC.00639-12","article-title":"HIV gp120 H375 is unique to HIV-1 subtype CRF01_AE and confers strong resistance to the entry inhibitor BMS-599793, a candidate microbicide drug","volume":"56","author":"Schader","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"2020051504585151100_dkaa034-B21","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.meegid.2014.02.007","article-title":"Identification of a new HIV-1 BC circulating recombinant form (CRF60_BC) in Italian young men having sex with men","volume":"23","author":"Simonetti","year":"2014","journal-title":"Infect Genet Evol"},{"key":"2020051504585151100_dkaa034-B22","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":"2020051504585151100_dkaa034-B23","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1128\/AAC.01173-10","article-title":"In vivo patterns of resistance to the HIV attachment inhibitor BMS-488043","volume":"55","author":"Zhou","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"2020051504585151100_dkaa034-B24","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1093\/jac\/dks067","article-title":"Prevalence of subtype-related polymorphisms associated with in vitro resistance to attachment inhibitor BMS-626529 in HIV-1 \u2018non-B\u2019-infected patients","volume":"67","author":"Charpentier","year":"2012","journal-title":"J Antimicrob Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/75\/6\/1580\/33213805\/dkaa034.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/75\/6\/1580\/33213805\/dkaa034.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T20:30:54Z","timestamp":1589661054000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/75\/6\/1580\/5810153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,19]]},"references-count":24,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,3,19]]},"published-print":{"date-parts":[[2020,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkaa034","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,6]]},"published":{"date-parts":[[2020,3,19]]}}}