{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:46:44Z","timestamp":1785851204274,"version":"3.56.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Gilead Sciences, Inc.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Remdesivir inhibits the SARS-CoV-2 RNA-dependent polymerase (Nsp12). Here, we present virology analyses from the Phase 3 REDPINE trial in participants with impaired kidney function hospitalized for COVID-19 and treated with remdesivir or placebo for 5 days. Out of 243 participants enrolled and treated in the study, 42 participants had solid organ transplantation (SOT) and received immunosuppressive medication prior to and during the study. Nasopharyngeal swabs were collected at baseline and through Day 29. Virology assessments were performed using SARS-CoV-2 RT-qPCR, next-generation sequencing, and site-directed mutagenesis in a SARS-CoV-2 replicon system. Remdesivir treatment demonstrated significantly greater reductions from baseline in viral load on Day 5 and Day 7 compared with placebo (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2264 0.034). In the remdesivir treatment group, participants with SOT showed significantly smaller viral load reductions from baseline on Days 5, 7, and 14 compared with participants without SOT (all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05). Mathematical modeling of viral load kinetics in participants with kidney transplants predicted a &gt;13-day faster time to viral load decline by extending the remdesivir treatment duration from 5 days to 10 days. In four participants treated with remdesivir, emergent substitutions in Nsp12 (E136V, M794I, and C799F) with low-level reduced\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      susceptibility to remdesivir (\u22643.4 fold change in half-maximal effective concentration) were observed 9 days after cessation of remdesivir treatment. Three of the four participants had undergone SOT. Overall, remdesivir demonstrated antiviral activity in participants with impaired kidney function, with delayed viral clearance in SOT recipients and rare posttreatment emergence of Nsp12 substitutions that confer low-level reduced susceptibility to remdesivir.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>CLINICAL TRIALS<\/jats:title>\n                      <jats:p>\n                        This study is registered with ClinicalTrials.gov as\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04745351\" xlink:type=\"simple\">NCT04745351<\/jats:ext-link>\n                        ; EudraCT registration no. 2020-005416-22.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01912-25","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:00:32Z","timestamp":1783695632000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Virologic insights from the phase 3 REDPINE trial: remdesivir in renally impaired and immunocompromised patients with COVID-19"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9124-4652","authenticated-orcid":true,"given":"Lauren","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc.","place":["Foster City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7201-533X","authenticated-orcid":true,"given":"Kristen","family":"Andreatta","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.","place":["Foster City, 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VEKLURY (remdesivir) [prescribing information]. https:\/\/www.gilead.com\/-\/media\/files\/pdfs\/medicines\/covid-19\/veklury\/veklury_pi.pdf."},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2007764"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.16349"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2116846"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae333"},{"key":"e_1_3_4_18_2","unstructured":"Gilead Sciences. 2023. FDA approves veklury (Remdesivir) for COVID-19 treatment in patients with severe renal impairment including those on dialysis. Available from: https:\/\/www.gilead.com\/news-and-press\/press-room\/press-releases\/2023\/7\/fda-approves-veklury-remdesivir-for-covid19-treatment-in-patients-with-severe-renal-impairment-including-those-on-dialysis"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.23749\/mdl.v113i2.12724"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(23)00336-1"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/irv.70121"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00221-X"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad270"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/v16040546"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01238-24"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.033"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00222-22"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae631.2181"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00198-22"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009929"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo0718"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51924-3"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29104-y"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac769"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02448-22"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19055-7"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104974"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01912-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01912-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:02:38Z","timestamp":1785848558000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01912-25"}},"subtitle":[],"editor":[{"given":"Zhaohui","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":36,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,5]]}},"alternative-id":["10.1128\/aac.01912-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.01912-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"assertion":[{"value":"2025-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01912-25"}}