{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T21:26:27Z","timestamp":1770326787224,"version":"3.49.0"},"reference-count":72,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Treatment options for individuals infected with human immunodeficiency virus type 2 (HIV-2) are restricted by the intrinsic resistance of the virus to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and the reduced susceptibility of HIV-2 to several protease inhibitors (PIs) used in antiretroviral therapy (ART). In an effort to identify new antiretrovirals for HIV-2 treatment, we evaluated the<jats:italic>in vitro<\/jats:italic>activity of the investigational nucleoside analog BMS-986001 (2\u2032,3\u2032-didehydro-3\u2032-deoxy-4\u2032-ethynylthymidine; also known as censavudine, festinavir, OBP-601, 4\u2032-ethynyl stavudine, or 4\u2032-ethynyl-d4T). In single-cycle assays, BMS-986001 inhibited HIV-2 isolates from treatment-naive individuals, with 50% effective concentrations (EC<jats:sub>50<\/jats:sub>s) ranging from 30 to 81 nM. In contrast, EC<jats:sub>50<\/jats:sub>s for group M and O isolates of HIV-1 ranged from 450 to 890 nM. Across all isolates tested, the average EC<jats:sub>50<\/jats:sub>for HIV-2 was 9.5-fold lower than that for HIV-1 (64 \u00b1 18 nM versus 610 \u00b1 200 nM, respectively; mean \u00b1 standard deviation). BMS-986001 also exhibited full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase, whereas the M184V mutant was 15-fold more resistant to the drug than the parental HIV-2<jats:sub>ROD9<\/jats:sub>strain. Taken together, our findings show that BMS-986001 is an effective inhibitor of HIV-2 replication. To our knowledge, BMS-986001 is the first nucleoside analog that, when tested against a diverse collection of HIV-1 and HIV-2 isolates, exhibits more potent activity against HIV-2 than against HIV-1 in culture.<\/jats:p>","DOI":"10.1128\/aac.01326-15","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T02:23:49Z","timestamp":1442888629000},"page":"7437-7446","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["The Nucleoside Analog BMS-986001 Shows Greater<i>In Vitro<\/i>Activity against HIV-2 than against HIV-1"],"prefix":"10.1128","volume":"59","author":[{"given":"Robert A.","family":"Smith","sequence":"first","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana N.","family":"Raugi","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent H.","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally S.","family":"Leong","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate M.","family":"Parker","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariah K.","family":"Oakes","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Papa Salif","family":"Sow","sequence":"additional","affiliation":[{"name":"Service des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selly","family":"Ba","sequence":"additional","affiliation":[{"name":"Service des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moussa","family":"Seydi","sequence":"additional","affiliation":[{"name":"Service des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey S.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"},{"name":"Department of Global Health, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"HIV\/AIDS fact sheets: FDA-approved HIV medicines","author":"United States Department of Health and Human Services","year":"2015","unstructured":"United States Department of Health and Human Services. 4 May 2015, posting date. HIV\/AIDS fact sheets: FDA-approved HIV medicines. United States Department of Health and Human Services, Washington, DC. http:\/\/aidsinfo.nih.gov\/education-materials\/fact-sheets\/19\/58\/fda-approved-hiv-medicines."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000243"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081355"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2008.09.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.12.001"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01284-07"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.10.013"},{"key":"e_1_3_3_9_2","first-page":"139","article-title":"Enfuvirtide, the first fusion inhibitor to treat HIV infection","volume":"7","author":"Poveda E","year":"2005","unstructured":"Poveda E, Briz V, Soriano V. 2005. Enfuvirtide, the first fusion inhibitor to treat HIV infection. AIDS Rev 7:139\u2013147.","journal-title":"AIDS Rev"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00405-13"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.2.305"},{"key":"e_1_3_3_12_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1177\/135965350400900115","article-title":"Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis","volume":"9","author":"Witvrouw M","year":"2004","unstructured":"Witvrouw M, Pannecouque C, Switzer WM, Folks TM, De Clercq E, Heneine W. 2004. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther 9:57\u201365.","journal-title":"Antivir Ther"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32833f9e36"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1988.4.107"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn335"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01004-07"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32834d8e52"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-015-0146-8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092747"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000244"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00942-10"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.1.484-487.2005"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1086\/596504"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32830f4c7d"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2009.06.020"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1086\/597802"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr164"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2009.0039"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2003.07.009"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.112.078758"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00083-08"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1640-1646.2004"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01195-13"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.8.3355-3360.2005"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1177\/095632020501600402"},{"key":"e_1_3_3_36_2","volume-title":"Abstr Intersci Conf Antimicrob Agents Chemother","author":"Gupta SK","year":"2014","unstructured":"Gupta SK, Lombaard J, Echevarria J, Orrell C, Avihingsanon A, Santoscoy M, Stock D, Joshi SR, Hanna GJ, Lataillade M. 2014. HIV NRTI BMS-986001 in antiretroviral-na\u00efve subjects: week 24\/48 analysis. Abstr Intersci Conf Antimicrob Agents Chemother, Washington, DC. American Society for Microbiology, Washington, DC. http:\/\/www.icaac.org\/."},{"key":"e_1_3_3_37_2","first-page":"880, 884\u2013886","article-title":"Reduction in growth temperature minimizes instability of large plasmids containing HIV-1 proviral genomes","volume":"14","author":"Joshi A","year":"1993","unstructured":"Joshi A, Jeang KT. 1993. Reduction in growth temperature minimizes instability of large plasmids containing HIV-1 proviral genomes. Biotechniques 14:880, 884\u2013886.","journal-title":"Biotechniques"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(196504)18:4<522::AID-CNCR2820180418>3.0.CO;2-J"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1987.3.283"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M314038200"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2008.0015"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr354"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02259-14"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057103256465"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5394.1669"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222366699"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22570"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0506s15"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(02)00344-5"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1994.10.1725"},{"key":"e_1_3_3_53_2","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1177\/135965350501000702","article-title":"In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene","volume":"10","author":"Damond F","year":"2005","unstructured":"Damond F, Collin G, Matheron S, Peytavin G, Campa P, Delarue S, Taieb A, Benard A, Chene G, Brun-Vezinet F, Descamps D, French ANRS HIV-2 Cohort (ANRS CO 5 VIH-2). 2005. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. Antivir Ther 10:861\u2013865.","journal-title":"Antivir Ther"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200009010-00002"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20174"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06597-11"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020010"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf637"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-461"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00686-09"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.04.007"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05036-14"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.562694"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2014.03.001"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200317003-00007"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-12-95"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32834c4adb"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00870-06"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/463704"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282f9b165"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-8-68"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(82)90515-0"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-7-70"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01326-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01326-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T03:18:40Z","timestamp":1653189520000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01326-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":72,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1128\/AAC.01326-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.01326-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]},"assertion":[{"value":"2015-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}