{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T22:12:14Z","timestamp":1761948734405},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Merck investigator grant","award":["58422"],"award-info":[{"award-number":["58422"]}]},{"name":"Fonds de Recherche du Qu\u00e9bec Sant\u00e9-R\u00e9seau SIDA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The newer generation NNRTIs, including doravirine and rilpivirine, were designed to show high potency and overcome K103N, Y181C and G190A resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To assess emergent resistance to doravirine and rilpivirine, alone and paired with lamivudine or islatravir through in vitro drug selections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Subtype B (n\u200a=\u200a3), non-B subtype (n\u200a=\u200a3), and pNL4.3 viral isolates were passaged in cord blood mononuclear cells with progressively increasing concentrations of drug(s). Genotypic analysis compared the acquisition and accumulation of drug resistance mutations at weeks 8 and 24 following drug pressure. Cell-based phenotypic assays assessed cross-resistance patterns to NNRTIs by acquired resistance mutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Doravirine pressure resulted in the acquisition of V108I (6\/7) and V106A\/I\/M (5\/7) mutations at weeks 8, followed by F227L (4\/7), Y318F (4\/7), M230L (2\/7) or L234I (2\/7) by weeks 24. In contrast, rilpivirine resulted in E138K (5\/7) followed by L100I (3\/7), K101E (1\/7), or M230L (1\/7). Doravirine resistance pathways retained susceptibility to rilpivirine, whereas rilpivirine resistance conferred intermediate resistance (12\u2013152-fold) to doravirine. Dual selections with islatravir or lamivudine delayed and diminished emergent resistance to doravirine, resulting in V108I (9\/15) with fewer or no other changes at weeks 24. There was a lesser delay in emergent resistance to rilpivirine when combined with islatravir or lamivudine. The M184V mutation did not arise in dual selections with islatravir or lamivudine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Doravirine showed a more robust resistance profile compared with other NNRTIs. The long intracellular half-life of islatravir and delayed acquisition of resistance in dual selections provide an opportunity for long-acting treatment options.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab126","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T19:14:23Z","timestamp":1617304463000},"page":"2137-2142","source":"Crossref","is-referenced-by-count":15,"title":["Cell culture selections reveal favourable drug resistance profiles for doravirine and islatravir"],"prefix":"10.1093","volume":"76","author":[{"given":"Bluma G","family":"Brenner","sequence":"first","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Oliveira","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, 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