{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:56:25Z","timestamp":1789473385523,"version":"build-2803163510"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Fulbright-CONICET Scholar Award to P.C.A.","award":["AI116167"],"award-info":[{"award-number":["AI116167"]}]},{"name":"Basic Science Core of the Texas D-CFAR","award":["AI161943"],"award-info":[{"award-number":["AI161943"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Islatravir is a new antiretroviral drug that inhibits the reverse transcriptase (RT) of HIV-1 through multiple mechanisms. It is proposed to be used in combination with doravirine, a new NNRTI. M184V\/I mutations have been shown to reduce the in vitro antiviral activity of islatravir, but their effect when pre-selected during ART has not been investigated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>HIV-1 rt sequences were obtained from four individuals of the Garrahan HIV cohort prior to, or during virological failure to ART. HIV-1 infectious molecular clones were constructed on an NL4-3 backbone, and infectious viruses were produced by transfection of 293T cells. Fold-changes in IC50 were calculated for each mutant versus the NL4-3 WT. HIV-1 phenotypic drug resistance was tested in vitro against NRTIs and NNRTIs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In all the cases, M184I\/V, either alone or in the presence of other mutations, was associated with reduced susceptibility to islatravir, abacavir and lamivudine. Viruses carrying M184V\/I showed variable levels of resistance to islatravir (4.8 to 33.8-fold). The greatest reduction in susceptibility was observed for viruses carrying the mutations M184V + V106I (33.8-fold resistance) or M184V + I142V (25.2-fold resistance). For NNRTIs, the presence of V106I alone did not affect susceptibility to doravirine or etravirine, but showed a modest reduction in susceptibility to efavirenz (6-fold). Susceptibility to doravirine was slightly reduced only for one of the mutants carrying V106I in combination with Y181C and M184V.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Mutations and polymorphisms selected in vivo together with M184V\/I depend on the viral genetic context and on ART history, and could affect the efficacy of islatravir once available for use in the clinic.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad390","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T13:13:38Z","timestamp":1703769218000},"page":"370-374","source":"Crossref","is-referenced-by-count":9,"title":["Variable antiviral activity of islatravir against M184I\/V mutant HIV-1 selected during antiretroviral therapy"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6760-842X","authenticated-orcid":false,"given":"Paula C","family":"Aulicino","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Biology and Retroviruses, Unit of Virology and Molecular Epidemiology, Hospital de Pediatr\u00eda Prof. Dr Juan P. Garrahan , Buenos Aires , Argentina"},{"name":"CONICET , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology & Microbiology, Baylor College of Medicine , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khanghy","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology & Microbiology, Baylor College of Medicine , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vindhya","family":"Kukunoor","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology & Microbiology, Baylor College of Medicine , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karm","family":"Ghei","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology & Microbiology, Baylor College of Medicine , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solange","family":"Arazi-Caillaud","sequence":"additional","affiliation":[{"name":"Unit of Epidemiology and Infectology, Hospital de Pediatr\u00eda Prof. Dr Juan P. Garrahan , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira","family":"Taicz","sequence":"additional","affiliation":[{"name":"Unit of Epidemiology and Infectology, Hospital de Pediatr\u00eda Prof. Dr Juan P. Garrahan , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Bologna","sequence":"additional","affiliation":[{"name":"Unit of Epidemiology and Infectology, Hospital de Pediatr\u00eda Prof. Dr Juan P. Garrahan , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mangano","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biology and Retroviruses, Unit of Virology and Molecular Epidemiology, Hospital de Pediatr\u00eda Prof. Dr Juan P. Garrahan , Buenos Aires , Argentina"},{"name":"CONICET , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0504-0090","authenticated-orcid":false,"given":"Jason T","family":"Kimata","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology & Microbiology, Baylor College of Medicine , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,28]]},"reference":[{"issue":"Suppl 8","key":"2024020113263211600_dkad390-B1","first-page":"e25187","article-title":"Efficacy of MK-8591 against diverse HIV-1 subtypes and NRTI-resistant clinical isolates","volume":"21","author":"Grobler","year":"2018","journal-title":"J Int AIDS Soc"},{"key":"2024020113263211600_dkad390-B2","doi-asserted-by":"crossref","first-page":"e0013322","DOI":"10.1128\/aac.00133-22","article-title":"Islatravir has a high barrier to resistance and exhibits a 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