{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:01:55Z","timestamp":1760853715460},"reference-count":43,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"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":[[2013,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>BMS-986001 is a novel HIV nucleoside reverse transcriptase inhibitor (NRTI). To date, little is known about its resistance profile. In order to examine the cross-resistance profile of BMS-986001 to NRTI mutations, a replicating virus system was used to examine specific amino acid mutations known to confer resistance to various NRTIs. In addition, reverse transcriptases from 19 clinical isolates with various NRTI mutations were examined in the Monogram PhenoSense HIV assay. In the site-directed mutagenesis studies, a virus containing a K65R substitution exhibited a 0.4-fold change in 50% effective concentration (EC<jats:sub>50<\/jats:sub>) versus the wild type, while the majority of viruses with the Q151M constellation (without M184V) exhibited changes in EC<jats:sub>50<\/jats:sub>versus wild type of 0.23- to 0.48-fold. Susceptibility to BMS-986001 was also maintained in an L74V-containing virus (0.7-fold change), while an M184V-only-containing virus induced a 2- to 3-fold decrease in susceptibility. Increasing numbers of thymidine analog mutation pattern 1 (TAM-1) pathway mutations correlated with decreases in susceptibility to BMS-986001, while viruses with TAM-2 pathway mutations exhibited a 5- to 8-fold decrease in susceptibility, regardless of the number of TAMs. A 22-fold decrease in susceptibility to BMS-986001 was observed in a site-directed mutant containing the T69 insertion complex. Common non-NRTI (NNRTI) mutations had little impact on susceptibility to BMS-986001. The results from the site-directed mutants correlated well with the more complicated genotypes found in NRTI-resistant clinical isolates. Data from clinical studies are needed to determine the clinically relevant resistance cutoff values for BMS-986001.<\/jats:p>","DOI":"10.1128\/aac.01195-13","type":"journal-article","created":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T04:14:23Z","timestamp":1377576863000},"page":"5500-5508","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["<i>In Vitro<\/i>Cross-Resistance Profile of Nucleoside Reverse Transcriptase Inhibitor (NRTI) BMS-986001 against Known NRTI Resistance Mutations"],"prefix":"10.1128","volume":"57","author":[{"given":"Zhufang","family":"Li","sequence":"first","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Terry","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Olds","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tricia","family":"Protack","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Deminie","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Minassian","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Nowicka-Sans","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongnian","family":"Sun","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ira","family":"Dicker","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carey","family":"Hwang","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Hopewell, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Lataillade","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George J.","family":"Hanna","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Krystal","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1177\/135965350300800605","article-title":"Nucleoside and nucleotide analogue reverse transcriptase inhibitors: a clinical review of antiretroviral resistance","volume":"8","author":"Gallant JE","year":"2003","unstructured":"GallantJEGerondelisPZWainbergMAShulmanNSHaubrichRHSt ClairMLanierERHellmannNSRichmanDD. 2003. Nucleoside and nucleotide analogue reverse transcriptase inhibitors: a clinical review of antiretroviral resistance. Antivir. Ther. 8:489\u2013506.","journal-title":"Antivir. Ther."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1640-1646.2004"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2006.10.002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3182965d12"},{"key":"e_1_3_2_6_2","volume-title":"AIDS 2012, 19th International AIDS Conference","author":"Wang F","year":"2012","unstructured":"WangFFlintO. 2012. The HIV NRTI BMS-986001 does not degrade mitochondrial DNA in long term primary cultures of cells isolated from human kidney, muscle and subcutaneous fat. 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