{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:02:11Z","timestamp":1784872931819,"version":"3.55.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Aidsfonds","award":["P-60804"],"award-info":[{"award-number":["P-60804"]}]},{"name":"Dutch Aidsfonds","award":["KIC\/01562148"],"award-info":[{"award-number":["KIC\/01562148"]}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes for Health Research","doi-asserted-by":"publisher","award":["HB1 164063"],"award-info":[{"award-number":["HB1 164063"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI147330"],"award-info":[{"award-number":["R01AI147330"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Mutations in the 3\u2032-polypurine tract (3\u2032PPT) of HIV-1 have been observed under pressure with two integrase strand transfer inhibitors, dolutegravir and cabotegravir. In the DOMONO randomized clinical trial, 3\u2032PPT mutations emerged in a participant who experienced treatment failure under dolutegravir monotherapy. To understand the basis for this rare mutational pathway, we examined baseline viral sequences and identified the K156N natural polymorphism. Given the role of K156 in viral DNA binding, the potential relationship between K156N and 3\u2032PPT mutations was further investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed the impact of K156N on integrase using in silico modelling and biochemical assays with recombinant proteins. Infectivity, replicative capacity, and drug susceptibility of viruses carrying K156N, 3\u2032PPT mutations, or both were measured. Viral evolution was assessed in cell culture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Structural models indicated that K156N altered viral DNA binding. K156N reduced strand transfer activity through decreased affinity for the LTR but increased 3\u2032-processing. The K156N virus had normal infectivity, whereas the 3\u2032PPT mutations decreased infectiousness sixfold and lowered maximal infectivity. K156N partially compensated for this defect, but maximal infectivity remained diminished. K156N also partially compensated for defects in replicative capacity imposed by 3\u2032PPT mutations. K156N alone did not confer resistance against dolutegravir, nor did it increase the modest (2.5-fold) resistance conferred by the 3\u2032PPT mutations. K156N alone promoted the spontaneous emergence of 3\u2032PPT mutations distinct from those seen in DOMONO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings establish a direct functional relationship between natural variation in HIV-1 integrase and the emergence of 3\u2032PPT mutations. People harbouring a virus with the K156N natural polymorphism may be predisposed to developing 3\u2032PPT mutations upon failure with DTG. However, the clinical relevance of this association remains to be established.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag033","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T12:21:20Z","timestamp":1768825280000},"source":"Crossref","is-referenced-by-count":1,"title":["Cooperation between HIV-1 integrase natural polymorphism K156N and 3\u2032PPT mutations in dolutegravir monotherapy failure"],"prefix":"10.1093","volume":"81","author":[{"given":"Jolieke A T","family":"van Osch","sequence":"first","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanda J C","family":"Voermans","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haajar","family":"Ouzerne","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia B H","family":"Cromme","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehikioya","family":"Azugbene","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Voskamp","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00eb","family":"Krullaars","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwan","family":"Mahmud","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J","family":"Overmars","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja U","family":"Gorska","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-9628","authenticated-orcid":false,"given":"Cynthia","family":"Lungu","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]},{"name":"Department of Pathology, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A M C","family":"van De Vijver","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob A","family":"Gruters","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J A","family":"van Kampen","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-9128","authenticated-orcid":false,"given":"Thibault","family":"Mespl\u00e8de","sequence":"additional","affiliation":[{"name":"Viroscience Department, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"2026072401114343600_dkag033-B1","doi-asserted-by":"publisher","first-page":"e593","DOI":"10.1016\/S2352-3018(20)30231-9","article-title":"End resistance to dolutegravir roll-out","volume":"7","author":"The Lancet Hiv","year":"2020","journal-title":"Lancet HIV"},{"key":"2026072401114343600_dkag033-B2","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1080\/14787210.2025.2529431","article-title":"How frequent is dolutegravir resistance?","volume":"23","author":"van Osch","year":"2025","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2026072401114343600_dkag033-B3","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1097\/QAD.0000000000004170","article-title":"Noncanonical HIV drug resistance mutations: need to close existing gaps","volume":"39","author":"Inzaule","year":"2025","journal-title":"AIDS"},{"key":"2026072401114343600_dkag033-B4","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1093\/infdis\/jiy176","article-title":"HIV-1 Resistance dynamics in patients with virologic failure to dolutegravir maintenance monotherapy","volume":"218","author":"Wijting","year":"2018","journal-title":"J Infect Dis"},{"key":"2026072401114343600_dkag033-B5","doi-asserted-by":"publisher","first-page":"e00006-18","DOI":"10.1128\/mBio.00006-18","article-title":"How polypurine tract changes in the HIV-1 RNA genome can cause resistance against the integrase inhibitor dolutegravir","volume":"9","author":"Das","year":"2018","journal-title":"MBio"},{"key":"2026072401114343600_dkag033-B6","doi-asserted-by":"publisher","first-page":"11244","DOI":"10.1073\/pnas.200139397","article-title":"HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase","volume":"97","author":"Espeseth","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026072401114343600_dkag033-B7","doi-asserted-by":"publisher","first-page":"15910","DOI":"10.1073\/pnas.1002346107","article-title":"Structure-based modeling of the functional HIV-1 intasome and its inhibition","volume":"107","author":"Krishnan","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026072401114343600_dkag033-B8","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature08784","article-title":"Retroviral intasome assembly and inhibition of DNA strand transfer","volume":"464","author":"Hare","year":"2010","journal-title":"Nature"},{"key":"2026072401114343600_dkag033-B9","doi-asserted-by":"publisher","first-page":"31186","DOI":"10.1074\/jbc.M704935200","article-title":"Changes to the HIV long terminal repeat and to HIV integrase differentially impact HIV integrase assembly, activity, and the binding of strand transfer inhibitors","volume":"282","author":"Dicker","year":"2007","journal-title":"J Biol Chem"},{"key":"2026072401114343600_dkag033-B10","doi-asserted-by":"publisher","first-page":"e00922-17","DOI":"10.1128\/mBio.00922-17","article-title":"Mutations located outside the integrase gene can confer resistance to HIV-1 integrase strand transfer inhibitors","volume":"8","author":"Malet","year":"2017","journal-title":"mBio"},{"key":"2026072401114343600_dkag033-B11","doi-asserted-by":"publisher","first-page":"e0036123","DOI":"10.1128\/jvi.00361-23","article-title":"HIV-1 3'-Polypurine tract mutations confer dolutegravir resistance by switching to an integration-independent replication mechanism via 1-LTR circles","volume":"97","author":"Dekker","year":"2023","journal-title":"J Virol"},{"key":"2026072401114343600_dkag033-B12","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1093\/jac\/dkp153","article-title":"Evolution of raltegravir resistance during therapy","volume":"64","author":"Sichtig","year":"2009","journal-title":"J Antimicrob Chemother"},{"key":"2026072401114343600_dkag033-B13","doi-asserted-by":"publisher","first-page":"e02432-20","DOI":"10.1128\/AAC.02432-20","article-title":"Mutations in the HIV-1 3'-polypurine tract and integrase strand transfer inhibitor resistance","volume":"65","author":"Wei","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2026072401114343600_dkag033-B14","doi-asserted-by":"publisher","first-page":"e00623-18","DOI":"10.1128\/mBio.00623-18","article-title":"Reply to Das and Berkhout, \u201chow polypurine tract changes in the HIV-1 RNA genome can cause resistance against the integrase inhibitor dolutegravir\u201d","volume":"9","author":"Malet","year":"2018","journal-title":"MBio"},{"key":"2026072401114343600_dkag033-B15","doi-asserted-by":"publisher","first-page":"e0067622","DOI":"10.1128\/jvi.00676-22","article-title":"Mutations in the 3'-PPT lead to HIV-1 replication without integration","volume":"96","author":"Richetta","year":"2022","journal-title":"J Virol"},{"key":"2026072401114343600_dkag033-B16","doi-asserted-by":"publisher","first-page":"e0033524","DOI":"10.1128\/jvi.00335-24","article-title":"Reverse transcription of HIV-1 2-LTR circle transcripts does frequently cause 3'-polypurine tract mutations implicated in dolutegravir resistance","volume":"98","author":"Dekker","year":"2024","journal-title":"J Virol"},{"key":"2026072401114343600_dkag033-B17","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.3390\/ijms21051553","article-title":"Variability in HIV-1 integrase gene and 3'-polypurine tract sequences in Cameroon clinical isolates, and implications for integrase inhibitors efficacy","volume":"21","author":"Acharya","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026072401114343600_dkag033-B18","doi-asserted-by":"publisher","first-page":"3440","DOI":"10.1093\/jac\/dkz377","article-title":"Variability of the HIV-1 3\u2019 polypurine tract (3'PPT) region and implication in integrase inhibitor resistance","volume":"74","author":"Malet","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2026072401114343600_dkag033-B19","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.3390\/pathogens10081027","article-title":"Limited HIV-1 subtype C nef 3'PPT variation in combination antiretroviral therapy naive and experienced people living with HIV in Botswana","volume":"10","author":"Seatla","year":"2021","journal-title":"Pathogens"},{"key":"2026072401114343600_dkag033-B20","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1097\/QAI.0000000000003435","article-title":"Characterizing HIV drug resistance in cases of vertical transmission in the VESTED randomized antiretroviral treatment trial","volume":"96","author":"Bishop","year":"2024","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2026072401114343600_dkag033-B21","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1093\/jac\/dkab448","article-title":"Specific mutations in the HIV-1 G-tract of the 3'-polypurine tract cause resistance to integrase strand transfer inhibitors","volume":"77","author":"Hachiya","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2026072401114343600_dkag033-B22","doi-asserted-by":"publisher","first-page":"2501","DOI":"10.3390\/v13122501","article-title":"INSTIs and NNRTIs potently inhibit HIV-1 polypurine tract mutants in a single round infection assay","volume":"13","author":"Smith","year":"2021","journal-title":"Viruses"},{"key":"2026072401114343600_dkag033-B23","doi-asserted-by":"publisher","first-page":"6849","DOI":"10.1093\/emboj\/16.22.6849","article-title":"Critical contacts between HIV-1 integrase and viral DNA identified by structure-based analysis and photo-crosslinking","volume":"16","author":"Jenkins","year":"1997","journal-title":"EMBO J"},{"key":"2026072401114343600_dkag033-B24","doi-asserted-by":"publisher","first-page":"19966","DOI":"10.1074\/jbc.M211711200","article-title":"Strategy to discriminate between high and low affinity bindings of human immunodeficiency virus, type 1 integrase to viral DNA","volume":"278","author":"Zargarian","year":"2003","journal-title":"J Biol Chem"},{"key":"2026072401114343600_dkag033-B25","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1177\/1934578X1501000129","article-title":"Mutagenesis of lysines 156 and 159 in human immunodeficiency virus type 1 integrase (IN) reveals differential interactions between these residues and different IN inhibitors","volume":"10","author":"Crosby","year":"2015","journal-title":"Nat Prod Commun"},{"key":"2026072401114343600_dkag033-B26","doi-asserted-by":"publisher","first-page":"4170","DOI":"10.1073\/pnas.95.8.4170","article-title":"Identification of a nucleotide binding site in HIV-1 integrase","volume":"95","author":"Drake","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026072401114343600_dkag033-B27","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1093\/jac\/dkx529","article-title":"Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir resistance","volume":"73","author":"Malet","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2026072401114343600_dkag033-B28","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s11908-012-0305-1","article-title":"HIV drug resistance and the advent of integrase inhibitors","volume":"15","author":"Quashie","year":"2013","journal-title":"Curr Infect Dis Rep"},{"key":"2026072401114343600_dkag033-B29","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1128\/JVI.78.4.1718-1729.2004","article-title":"Novel single-cell-level phenotypic assay for residual drug susceptibility and reduced replication capacity of drug-resistant human immunodeficiency virus type 1","volume":"78","author":"Zhang","year":"2004","journal-title":"J Virol"},{"key":"2026072401114343600_dkag033-B30","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1128\/jvi.59.2.284-291.1986","article-title":"Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone","volume":"59","author":"Adachi","year":"1986","journal-title":"J Virol"},{"key":"2026072401114343600_dkag033-B31","doi-asserted-by":"publisher","first-page":"e0138622","DOI":"10.1128\/aac.01386-22","article-title":"The G118R plus R263K combination of integrase mutations associated with dolutegravir-based treatment failure reduces HIV-1 replicative capacity and integration","volume":"67","author":"Xiao","year":"2023","journal-title":"Antimicrob Agents Ch"},{"key":"2026072401114343600_dkag033-B32","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.3390\/v15112236","article-title":"Genotypic and phenotypic characterization of replication-competent HIV-2 isolated from controllers and progressors","volume":"15","author":"Lungu","year":"2023","journal-title":"Viruses-Basel"},{"key":"2026072401114343600_dkag033-B33","doi-asserted-by":"publisher","first-page":"168557","DOI":"10.1016\/j.jmb.2024.168557","article-title":"HIV-1 Integrase assembles multiple Species of stable synaptic Complex intasomes that are active for concerted DNA integration in vitro","volume":"436","author":"Li","year":"2024","journal-title":"J Mol Biol"},{"key":"2026072401114343600_dkag033-B34","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.3390\/v16071166","article-title":"HIV-1 Intasomes assembled with excess integrase C-terminal domain protein facilitate structural studies by cryo-EM and reveal the role of the integrase C-terminal tail in HIV-1 integration","volume":"16","author":"Li","year":"2024","journal-title":"Viruses-Basel"},{"key":"2026072401114343600_dkag033-B35","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1126\/science.aay8015","article-title":"Structural basis for strand-transfer inhibitor binding to HIV intasomes","volume":"367","author":"Passos","year":"2020","journal-title":"Science"},{"key":"2026072401114343600_dkag033-B36","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1016\/j.bpj.2011.10.024","article-title":"Improving the physical realism and structural accuracy of protein models by a two-step atomic-level energy minimization","volume":"101","author":"Xu","year":"2011","journal-title":"Biophys J"},{"key":"2026072401114343600_dkag033-B37","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1093\/jac\/dkaa471","article-title":"Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir","volume":"76","author":"Pham","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"2026072401114343600_dkag033-B38","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"2026072401114343600_dkag033-B39","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.jviromet.2012.05.003","article-title":"A high-throughput assay for HIV-1 integrase 3'-processing activity using time-resolved fluorescence","volume":"184","author":"Han","year":"2012","journal-title":"J Virol Methods"},{"key":"2026072401114343600_dkag033-B40","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1111\/j.1745-7254.2007.00561.x","article-title":"High-throughput real-time assay based on molecular beacons for HIV-1 integrase 3'-processing reaction","volume":"28","author":"He","year":"2007","journal-title":"Acta Pharmacol Sin"},{"key":"2026072401114343600_dkag033-B41","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.jviromet.2012.06.015","article-title":"Low cost HIV-1 quantitative RT-PCR assay in resource-limited settings: improvement and implementation","volume":"185","author":"Fibriani","year":"2012","journal-title":"J Virol Methods"},{"key":"2026072401114343600_dkag033-B42","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/978-1-59745-170-3_29","article-title":"Isolation of drug-resistant mutant HIV variants using tissue culture drug selection","volume":"485","author":"Oliveira","year":"2009","journal-title":"Methods Mol Biol"},{"key":"2026072401114343600_dkag033-B43","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.1128\/JVI.06591-11","article-title":"Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir","volume":"86","author":"Quashie","year":"2012","journal-title":"J Virol"},{"key":"2026072401114343600_dkag033-B44","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1093\/jac\/dku199","article-title":"Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity","volume":"69","author":"Mespl\u00e8de","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2026072401114343600_dkag033-B45","doi-asserted-by":"publisher","first-page":"6223","DOI":"10.1128\/AAC.01835-13","article-title":"Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase","volume":"57","author":"Quashie","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"2026072401114343600_dkag033-B46","doi-asserted-by":"publisher","first-page":"3163","DOI":"10.1128\/JVI.03353-14","article-title":"Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase","volume":"89","author":"Quashie","year":"2015","journal-title":"J Virol"},{"key":"2026072401114343600_dkag033-B47","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1093\/infdis\/jiy175","article-title":"The S230R integrase substitution associated with virus load rebound during dolutegravir monotherapy confers low-level resistance to integrase strand-transfer inhibitors","volume":"218","author":"Pham","year":"2018","journal-title":"J Infect Dis"},{"key":"2026072401114343600_dkag033-B48","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1124\/mol.111.073189","article-title":"Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S\/GSK1349572)","volume":"80","author":"Hare","year":"2011","journal-title":"Mol Pharmacol"},{"key":"2026072401114343600_dkag033-B49","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1111\/j.1742-4658.2006.05139.x","article-title":"Kinetic study of the HIV-1 DNA 3'-end processing","volume":"273","author":"Smolov","year":"2006","journal-title":"FEBS J"},{"key":"2026072401114343600_dkag033-B50","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1126\/science.aah5163","article-title":"Cryo-EM structures and atomic model of the HIV-1 strand transfer complex intasome","volume":"355","author":"Passos","year":"2017","journal-title":"Science"},{"key":"2026072401114343600_dkag033-B51","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/1742-4690-5-74","article-title":"Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors","volume":"5","author":"Rhee","year":"2008","journal-title":"Retrovirology"},{"key":"2026072401114343600_dkag033-B52","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1177\/135965350701200411","article-title":"Natural polymorphism of the HIV-1 integrase gene and mutations associated with integrase inhibitor resistance","volume":"12","author":"Lataillade","year":"2007","journal-title":"Antivir Ther"},{"key":"2026072401114343600_dkag033-B53","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1093\/jac\/dkp423","article-title":"Integrase variability and susceptibility to HIV integrase inhibitors: impact of subtypes, antiretroviral experience and duration of HIV infection","volume":"65","author":"Garrido","year":"2010","journal-title":"J Antimicrob Chemother"},{"key":"2026072401114343600_dkag033-B54","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s12977-018-0440-3","article-title":"Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir","volume":"15","author":"Oliveira","year":"2018","journal-title":"Retrovirology"},{"key":"2026072401114343600_dkag033-B55","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1186\/s13104-018-3492-5","article-title":"Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco","volume":"11","author":"Alaoui","year":"2018","journal-title":"BMC Res Notes"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/3\/dkag033\/66745893\/dkag033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/3\/dkag033\/66745893\/dkag033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:11:49Z","timestamp":1784869909000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkag033\/8459083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,2,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkag033","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,2,2]]},"article-number":"dkag033"}}