{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:22:08Z","timestamp":1784949728735,"version":"3.55.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"26th Conference on Retroviruses and Opportunistic Infections"},{"name":"CROI","award":["#548"],"award-info":[{"award-number":["#548"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Fostemsavir is the prodrug of the HIV-1 attachment inhibitor temsavir and is currently under clinical assessment in heavily treatment-experienced patients with limited therapeutic options. We evaluated the genotypic and phenotypic susceptibility to temsavir in a panel of samples collected from patients harbouring MDR strains enrolled in the Italian PRESTIGIO Registry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Plasma samples from 24 patients were used for HIV-1 gp120 sequencing, while viral tropism and susceptibility to temsavir were assessed through a homemade phenotypic assay with pseudotyped viruses expressing patient-derived Env protein.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of the 24 patients enrolled, 18 (75%) were male, median (IQR) age was 55\u2009years (52\u201361), time since HIV-1 diagnosis was 27\u2009years (24\u201330), time on ART was 26\u2009years (23\u201327) and 11 (46%) had a previous AIDS diagnosis. Exposure to entry inhibitors (maraviroc and\/or enfuvirtide) had occurred in 19 (79%) patients. Among 23\/24 gp120 sequences obtained, temsavir resistance-associated mutations (RAMs) were detected in three cases (two M426L and one S375N). Pseudotyped viruses were obtained from 23\/24 samples and viral tropism was CXCR4-tropic, CCR5-tropic and dual\/mixed-tropic in six, nine and eight cases, respectively. Phenotypic susceptibility to temsavir was comparable to the reference WT viruses NL4-3 and AD8 in all samples, irrespective of RAMs. Viral tropism and exposure to entry inhibitors did not impact temsavir susceptibility.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data support the use of fostemsavir as a valuable therapy option in patients harbouring MDR virus. The role of laboratory testing in optimal screening of patients eligible for fostemsavir treatment remains to be investigated.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa178","type":"journal-article","created":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T19:13:02Z","timestamp":1586891582000},"page":"2547-2553","source":"Crossref","is-referenced-by-count":16,"title":["In vitro susceptibility to fostemsavir is not affected by long-term exposure to antiviral therapy in MDR HIV-1-infected patients"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9934-377X","authenticated-orcid":false,"given":"Francesco","family":"Saladini","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Giannini","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Giammarino","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Maggiolo","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vichi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Santa Maria Annunziata Hospital, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio M","family":"Corbelli","sequence":"additional","affiliation":[{"name":"Plus Onlus, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Galli","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Bigoloni","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Poli","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Zazzi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Castagna","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute, Milan, Italy"},{"name":"Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,28]]},"reference":[{"key":"2020082404572469800_dkaa178-B1","author":"Lataillade","year":"2019"},{"key":"2020082404572469800_dkaa178-B2","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/prot.24726","article-title":"Homology models of the HIV-1 attachment inhibitor BMS-626529 bound to gp120 suggest a unique mechanism of action","volume":"83","author":"Langley","year":"2015","journal-title":"Proteins"},{"key":"2020082404572469800_dkaa178-B3","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":"2020082404572469800_dkaa178-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":"2020082404572469800_dkaa178-B5","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":"2020082404572469800_dkaa178-B6","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"},{"key":"2020082404572469800_dkaa178-B7","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":"2020082404572469800_dkaa178-B8","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":"2020082404572469800_dkaa178-B9","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"},{"key":"2020082404572469800_dkaa178-B10","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":"2020082404572469800_dkaa178-B11","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":"2020082404572469800_dkaa178-B12","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jviromet.2010.06.012","article-title":"The design and validation of a novel phenotypic assay to determine HIV-1 coreceptor usage of clinical isolates","volume":"169","author":"Lin","year":"2010","journal-title":"J Virol Methods"},{"key":"2020082404572469800_dkaa178-B13","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jcv.2018.12.007","article-title":"Performance of Geno2Pheno[coreceptor] to infer coreceptor use in human immunodeficiency virus type 1 (HIV-1) subtype A","volume":"111","author":"Vicenti","year":"2019","journal-title":"J Clin Virol"},{"key":"2020082404572469800_dkaa178-B14","doi-asserted-by":"crossref","first-page":"e144","DOI":"10.1093\/nar\/gku739","article-title":"COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification","volume":"42","author":"Struck","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2020082404572469800_dkaa178-B15","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S1473-3099(10)70319-4","article-title":"European guidelines on the clinical management of HIV-1 tropism testing","volume":"11","author":"Vandekerckhove","year":"2011","journal-title":"Lancet Infect Dis"},{"key":"2020082404572469800_dkaa178-B16","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":"2020082404572469800_dkaa178-B17","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1128\/JCM.01611-07","article-title":"Evaluation of eight different bioinformatics tools to predict viral tropism in different human immunodeficiency virus type 1 subtypes","volume":"46","author":"Garrido","year":"2008","journal-title":"J Clin Microbiol"},{"key":"2020082404572469800_dkaa178-B18","doi-asserted-by":"crossref","first-page":"F11","DOI":"10.1097\/QAD.0b013e32830ebcd4","article-title":"Correlation between genotypic predictions based on V3 sequences and phenotypic determination of HIV-1 tropism","volume":"22","author":"Raymond","year":"2008","journal-title":"AIDS"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/75\/9\/2547\/33665052\/dkaa178.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/75\/9\/2547\/33665052\/dkaa178.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T08:57:40Z","timestamp":1598259460000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/75\/9\/2547\/5848382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,28]]},"references-count":18,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,5,28]]},"published-print":{"date-parts":[[2020,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkaa178","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9]]},"published":{"date-parts":[[2020,5,28]]}}}