{"doi":"10.1186/s12977-015-0146-8","title":"In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2","abstract":null,"journal":"Retrovirology","year":2015,"id":621041,"datarank":0.5495342469194471,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.0,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1603465,"name":"Robert A Smith","orcid":null,"position":1,"is_corresponding":false},{"id":1603468,"name":"Dana N Raugi","orcid":null,"position":2,"is_corresponding":false},{"id":416982,"name":"Charlotte Pan","orcid":null,"position":3,"is_corresponding":false},{"id":415812,"name":"Papa Salif Sow","orcid":"0000-0003-3137-1368","position":4,"is_corresponding":false},{"id":259097,"name":"Moussa Seydi","orcid":"0000-0002-0977-1085","position":5,"is_corresponding":false},{"id":1519482,"name":"James I Mullins","orcid":null,"position":6,"is_corresponding":false},{"id":1603472,"name":"Geoffrey S Gottlieb","orcid":null,"position":7,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2","abstract":"BACKGROUND: Dolutegravir recently became the third integrase strand transfer inhibitor (INSTI) approved for use in HIV-1-infected individuals. In contrast to the extensive dataset for HIV-1, in vitro studies and clinical reports of dolutegravir for HIV-2 are limited. To evaluate the potential role of dolutegravir in HIV-2 treatment, we compared the susceptibilities of wild-type and INSTI-resistant HIV-1 and HIV-2 strains to the drug using single-cycle assays, spreading infections of immortalized T cells, and site-directed mutagenesis. FINDINGS: HIV-2 group A, HIV-2 group B, and HIV-1 isolates from INSTI-naïve individuals were comparably sensitive to dolutegravir in the single-cycle assay (mean EC50 values = 1.9, 2.6, and 1.3 nM, respectively). Integrase substitutions E92Q, Y143C, E92Q + Y143C, and Q148R conferred relatively low levels of resistance to dolutegravir in HIV-2ROD9 (2- to 6-fold), but Q148K, E92Q + N155H, T97A + N155H and G140S + Q148R resulted in moderate resistance (10- to 46-fold), and the combination of T97A + Y143C in HIV-2ROD9 conferred high-level resistance (>5000-fold). In contrast, HIV-1NL4-3 mutants E92Q + N155H, G140S + Q148R, and T97A + Y143C showed 2-fold, 4-fold, and no increase in EC50, respectively, relative to the parental strain. The resistance phenotypes for E92Q + N155H, and G140S + Q148R HIV-2ROD9 were also confirmed in spreading infections of CEM-ss cells. CONCLUSIONS: Our data support the use of dolutegravir in INSTI-naïve HIV-2 patients but suggest that, relative to HIV-1, a broader array of replacements in HIV-2 integrase may enable cross-resistance between dolutegravir and other INSTI. Clinical studies are needed to evaluate the efficacy of dolutegravir in HIV-2-infected individuals, including patients previously treated with raltegravir or elvitegravir.","is_dataset_classified":null,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25808007","pmcid":"PMC4328052","openalex_id":"https://openalex.org/W2097661677","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"2R01-AI060466","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P30 AI027757","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI060466","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01AI060466-10","title":"Antiretroviral Therapy for HIV-2 Infection in Senegal"},{"funder_name":"National Institutes of Health","grant_id":"5P30AI027757-18","title":"University of Washington Center for AIDS Research"},{"funder_name":"National Institutes of Health","grant_id":"3P30AI027757-36S1","title":"University of Washington/Fred Hutch Center for AIDS Research"}],"total_grants":6,"fwci":3.0203,"citation_percentile":0.91507077,"influential_citations":0,"citation_trend":[{"year":2015,"count":4},{"year":2016,"count":4},{"year":2017,"count":3},{"year":2018,"count":5},{"year":2019,"count":4},{"year":2020,"count":6},{"year":2021,"count":2},{"year":2022,"count":3},{"year":2023,"count":4},{"year":2024,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://retrovirology.biomedcentral.com/counter/pdf/10.1186/s12977-015-0146-8","host_type":"journal"},{"url":"https://retrovirology.biomedcentral.com/counter/pdf/10.1186/s12977-015-0146-8","host_type":"publisher"},{"url":"http://link.springer.com/content/pdf/10.1186/s12977-015-0146-8.pdf","host_type":"publisher"},{"url":"http://link.springer.com/article/10.1186/s12977-015-0146-8/fulltext.html","host_type":"publisher"},{"url":"http://link.springer.com/content/pdf/10.1186/s12977-015-0146-8","host_type":"publisher"},{"url":"https://doi.org/10.1186/s12977-015-0146-8","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25808007","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4328052","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4328052","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4328052?pdf=render","host_type":"Europe_PMC"},{"url":"https://retrovirology.biomedcentral.com/track/pdf/10.1186/s12977-015-0146-8","host_type":""},{"url":"http://dx.doi.org/10.1186/s12977-015-0146-8","host_type":""},{"url":"https://dx.doi.org/10.1186/s12977-015-0146-8","host_type":""}],"fields_of_study":["HIV/AIDS drug development and treatment","Biochemical and Molecular Research","Pneumocystis jirovecii pneumonia detection and treatment","0301 basic medicine","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Dolutegravir","Heterocyclic Compounds, 3-Ring","Humans","Microbial Sensitivity Tests","Oxazines","Piperazines","Pyridones","HIV-1","HIV-2","Anti-HIV Agents","Drug Resistance, Viral"],"keywords":["Dolutegravir","Integrase","Integrase inhibitor","Virology","Human immunodeficiency virus (HIV)","Medicine","Drug resistance","Antiretroviral therapy","Viral load","Biology","Genetics","Anti-HIV Agents","Pyridones","Short Report","Microbial Sensitivity Tests","Piperazines","Infectious Diseases","Drug Resistance, Viral","HIV-2","Oxazines","HIV-1","Humans","Heterocyclic Compounds, 3-Ring"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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