{"doi":"10.1093/jac/dkx195","title":"Monotherapy with either dolutegravir or raltegravir fails to durably suppress HIV viraemia in humanized mice","abstract":null,"journal":"Journal of Antimicrobial Chemotherapy","year":2017,"id":601979,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"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":1530493,"name":"Said Hassounah","orcid":null,"position":1,"is_corresponding":false},{"id":1543681,"name":"Sandra Medina-Moreno","orcid":null,"position":2,"is_corresponding":false},{"id":1543682,"name":"Juan C. Zapata","orcid":null,"position":3,"is_corresponding":false},{"id":1543683,"name":"Nhut M. Le","orcid":null,"position":4,"is_corresponding":false},{"id":1530495,"name":"Yingshan Han","orcid":null,"position":5,"is_corresponding":false},{"id":1543684,"name":"James S. Foulke","orcid":null,"position":6,"is_corresponding":false},{"id":536387,"name":"Charles Davis","orcid":"0000-0002-4080-8579","position":7,"is_corresponding":false},{"id":436789,"name":"Joseph Bryant","orcid":null,"position":8,"is_corresponding":false},{"id":316715,"name":"Robert R. Redfield","orcid":"0000-0001-5986-3466","position":9,"is_corresponding":false},{"id":1516254,"name":"Mark A. Wainberg","orcid":null,"position":10,"is_corresponding":false},{"id":451490,"name":"Alonso Heredia","orcid":"0000-0001-7468-8504","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Monotherapy with either dolutegravir or raltegravir fails to durably suppress HIV viraemia in humanized mice","abstract":"Objectives: To compare the effectiveness of HIV integrase inhibitor monotherapy between raltegravir and dolutegravir as an approach to simplify therapy. Methods: We evaluated and compared the efficacy of 20 week monotherapy with dolutegravir or raltegravir in humanized mice (HSC-NSG) infected with HIVBaL. Plasma HIV RNA was measured by quantitative RT-PCR (limit of detection of 150 copies/45 μL of plasma) and drug levels by LC-MS/MS. Escape viruses were genotyped and analysed for replication capacity and drug susceptibility in tissue culture. Results: Drug-untreated control mice maintained constant viraemia throughout the study. Virus isolates from these mice were susceptible to both raltegravir (EC50 of <8 nM) and dolutegravir (EC50 of <1 nM). Mice treated with raltegravir or dolutegravir had plasma drug levels comparable to those in humans. Monotherapy with raltegravir initially suppressed HIV viraemia, but failed to maintain suppression in 4/4 mice. Viruses from raltegravir failing mice developed mutations G140G/S and Q148H/K, and were resistant to both raltegravir (EC50 values of >100 nM) and dolutegravir (EC50 values ranging from 8.8 to 13.3 nM). Monotherapy with dolutegravir suppressed viraemia in 5/5 of mice, but viraemia rebounded in one animal. The virus from this mouse had mutations E138K, G140S, Q148H, N155H and S230R, was highly resistant to both raltegravir (EC50 of >1000 nM) and dolutegravir (EC50 of 550 nM), and replicated to levels similar to those of control viruses in PBMCs. Conclusions: Monotherapy with either raltegravir or dolutegravir does not consistently maintain HIV suppression, suggesting that dual therapy may be required in simplification strategies.","is_dataset_classified":null,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28637235","pmcid":"PMC5890682","openalex_id":"https://openalex.org/W2626729825","authors":[],"funders":[{"funder_name":"Canadian Institutes of Health Research","grant_id":"unidentified","title":"unidentified"},{"funder_name":"CIHR","grant_id":"","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"","title":null}],"total_grants":3,"fwci":1.6021,"citation_percentile":0.82137737,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":5},{"year":2019,"count":1},{"year":2020,"count":3},{"year":2021,"count":3},{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/jac/article-pdf/72/9/2570/24332466/dkx195.pdf","host_type":"journal"},{"url":"https://academic.oup.com/jac/article-pdf/72/9/2570/24332466/dkx195.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/jac/article-pdf/72/9/2570/24332466/dkx195.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/jac/dkx195","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28637235","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC5890682","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5890682","host_type":"repository"},{"url":"https://dx.doi.org/10.1093/jac/dkx195","host_type":""}],"fields_of_study":["HIV/AIDS drug development and treatment","HIV Research and Treatment","HIV-related health complications and treatments","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Raltegravir Potassium","Dolutegravir","Animals","Genotype","Heterocyclic Compounds, 3-Ring","Humans","Mice, Transgenic","Mutation","Oxazines","Piperazines","Pyridones","RNA, Viral","Viremia","Virus Replication","HIV-1","HIV Infections","Anti-HIV Agents","HIV Integrase Inhibitors","Mice"],"keywords":["Dolutegravir","Raltegravir","Integrase inhibitor","Virology","Viral load","Pharmacology","Viral replication","Integrase","Biology","Medicine","Virus","Human immunodeficiency virus (HIV)","Antiretroviral therapy","Genotype","Anti-HIV Agents","Pyridones","HIV Infections","Mice, Transgenic","Virus Replication","Piperazines","Mice","Raltegravir Potassium","Mutation","Oxazines","HIV-1","Animals","Humans","RNA, Viral","HIV Integrase Inhibitors","Viremia","Heterocyclic Compounds, 3-Ring"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T17:55:57.706268Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}