{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:28:50Z","timestamp":1780486130321,"version":"3.54.1"},"reference-count":35,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>4\u2032-Ethynyl-2-fluoro-2\u2032-deoxyadenosine (EFdA) contains an ethynyl moiety and the 3\u2032-hydroxyl and exerts highly potent activity against various HIV type-1 (HIV-1) strains including multi-drug-resistant variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Comparative selection passages against EFdA, lamivudine (3TC), tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) or BMS-986001 (Ed4T) were conducted using a mixture of 11 highly multi-drug-resistant clinical HIV-1 isolates (HIV\n                      <jats:sub>11MIX<\/jats:sub>\n                      ) as a starting virus population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Before selection, HIV\n                      <jats:sub>11MIX<\/jats:sub>\n                      was sensitive to EFdA with a 50% inhibitory concentration (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) of 0.032 \u03bcM, less susceptible to TDF and Ed4T with IC\n                      <jats:sub>50<\/jats:sub>\n                      s of 0.57 and 2.6 \u03bcM, respectively, and highly resistant to 3TC and FTC with IC\n                      <jats:sub>50<\/jats:sub>\n                      s&gt;10 \u03bcM. IC\n                      <jats:sub>50<\/jats:sub>\n                      s of TDF against HIV\n                      <jats:sub>11MIX<\/jats:sub>\n                      exposed to EFdA and TDF for 17 (HIV\n                      <jats:sub>11MIX<\/jats:sub>\n                      <jats:sup>EFdA-P17<\/jats:sup>\n                      ) and 14 (HIV\n                      <jats:sub>11MIX<\/jats:sub>\n                      <jats:sup>TDF-P14<\/jats:sup>\n                      ) passages were 8 and &gt;10 \u03bcM, respectively, while EFdA remained active against HIV\n                      <jats:sub>11MIX<\/jats:sub>\n                      <jats:sup>EFdA-P17<\/jats:sup>\n                      and HIV\n                      <jats:sub>11MIX<\/jats:sub>\n                      <jats:sup>TDF-P14<\/jats:sup>\n                      with IC\n                      <jats:sub>50<\/jats:sub>\n                      s of 0.15 and 0.1 \u03bcM, respectively. Both selected variants were highly resistant against zidovudine, 3TC, Ed4T and FTC (IC\n                      <jats:sub>50<\/jats:sub>\n                      values &gt;10 \u03bcM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The present data demonstrate that HIV\n                      <jats:sub>11MIX<\/jats:sub>\n                      developed resistance more rapidly against 3TC, FTC, TDF and Ed4T than against EFdA and that EFdA remained substantially active against TDF- and EFdA-selected variants. Thus, EFdA has a favourable resistance profile and represents a potentially promising new-generation nucleoside reverse transcriptase inhibitor.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp2697","type":"journal-article","created":{"date-parts":[[2013,10,25]],"date-time":"2013-10-25T14:54:05Z","timestamp":1382712845000},"page":"179-189","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["Delayed Emergence of HIV-1 Variants Resistant to 4\u2032-Ethy Nyl-2-Fluoro-2\u2032-Deoxyadenosine: Comparative Sequential Passage Study with Lamivudine, Tenofovir, Emtricitabine and BMS-986001"],"prefix":"10.1177","volume":"19","author":[{"given":"Kenji","family":"Maeda","sequence":"first","affiliation":[{"name":"Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshan V","family":"Desai","sequence":"additional","affiliation":[{"name":"Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Japan"},{"name":"Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotomo","family":"Nakata","sequence":"additional","affiliation":[{"name":"Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"},{"name":"Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi N","family":"Kodama","sequence":"additional","affiliation":[{"name":"Division of Emerging Infectious Diseases, Tohoku University Hospital, Tohoku Medical Megabank Organization, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Mitsuya","sequence":"additional","affiliation":[{"name":"Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"},{"name":"Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Kumamoto, 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