{"doi":"10.1093/jac/dkac430","title":"Frequency matters: comparison of drug resistance mutation detection by Sanger and next-generation sequencing in HIV-1","abstract":"BACKGROUND: Next-generation sequencing (NGS) is gradually replacing Sanger sequencing (SS) as the primary method for HIV genotypic resistance testing. However, there are limited systematic data on comparability of these methods in a clinical setting for the presence of low-abundance drug resistance mutations (DRMs) and their dependency on the variant-calling thresholds. METHODS: To compare the HIV-DRMs detected by SS and NGS, we included participants enrolled in the Swiss HIV Cohort Study (SHCS) with SS and NGS sequences available with sample collection dates ≤7 days apart. We tested for the presence of HIV-DRMs and compared the agreement between SS and NGS at different variant-calling thresholds. RESULTS: We included 594 pairs of SS and NGS from 527 SHCS participants. Males accounted for 80.5% of the participants, 76.3% were ART naive at sample collection and 78.1% of the sequences were subtype B. Overall, we observed a good agreement (Cohen's kappa >0.80) for HIV-DRMs for variant-calling thresholds ≥5%. We observed an increase in low-abundance HIV-DRMs detected at lower thresholds [28/417 (6.7%) at 10%-25% to 293/812 (36.1%) at 1%-2% threshold]. However, such low-abundance HIV-DRMs were overrepresented in ART-naive participants and were in most cases not detected in previously sampled sequences suggesting high sequencing error for thresholds <3%. CONCLUSIONS: We found high concordance between SS and NGS but also a substantial number of low-abundance HIV-DRMs detected only by NGS at lower variant-calling thresholds. Our findings suggest that a substantial fraction of the low-abundance HIV-DRMs detected at thresholds <3% may represent sequencing errors and hence should not be overinterpreted in clinical practice.","journal":"Journal of Antimicrobial Chemotherapy","year":2023,"id":336880,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"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":0.934,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1018176,"name":"Tom Loosli","orcid":"0000-0003-2049-3562","position":1,"is_corresponding":false},{"id":1067833,"name":"Maryam Zaheri","orcid":"0000-0003-2777-835X","position":2,"is_corresponding":false},{"id":1068267,"name":"Paul Frischknecht","orcid":null,"position":3,"is_corresponding":false},{"id":459800,"name":"Michael Huber","orcid":"0000-0002-0384-0000","position":4,"is_corresponding":false},{"id":374346,"name":"Katharina Kusejko","orcid":"0000-0002-4638-1940","position":5,"is_corresponding":false},{"id":459802,"name":"Sabine Yerly","orcid":"0000-0003-1668-696X","position":6,"is_corresponding":false},{"id":780246,"name":"Karoline Leuzinger","orcid":"0000-0002-5654-9356","position":7,"is_corresponding":false},{"id":459801,"name":"Matthieu Perreau","orcid":"0000-0003-2110-2244","position":8,"is_corresponding":false},{"id":780247,"name":"Alban Ramette","orcid":"0000-0002-3437-4639","position":9,"is_corresponding":false},{"id":477373,"name":"Chris Wymant","orcid":"0000-0002-9847-8226","position":10,"is_corresponding":false},{"id":392159,"name":"Christophe Fraser","orcid":"0000-0003-2399-9657","position":11,"is_corresponding":false},{"id":225391,"name":"Paul Kellam","orcid":"0000-0003-3166-4734","position":12,"is_corresponding":false},{"id":105337,"name":"Astrid Gall","orcid":"0000-0001-6452-5816","position":13,"is_corresponding":false},{"id":345769,"name":"Hans H. Hirsch","orcid":"0000-0003-0883-0423","position":14,"is_corresponding":false},{"id":844662,"name":"Marcel Stoeckle","orcid":"0000-0002-0088-5078","position":15,"is_corresponding":false},{"id":459826,"name":"Andri Rauch","orcid":"0000-0001-5297-6062","position":16,"is_corresponding":false},{"id":459803,"name":"Matthias Cavassini","orcid":"0000-0003-0933-7833","position":17,"is_corresponding":false},{"id":218065,"name":"Enos Bernasconi","orcid":"0000-0002-9724-8373","position":18,"is_corresponding":false},{"id":932904,"name":"Julia Notter","orcid":"0000-0003-4821-9995","position":19,"is_corresponding":false},{"id":364611,"name":"Alexandra Calmy","orcid":"0000-0002-1137-6826","position":20,"is_corresponding":false},{"id":69678,"name":"Huldrych F. Gunthard","orcid":"0000-0002-1142-6723","position":21,"is_corresponding":false},{"id":437382,"name":"Karin J. Metzner","orcid":"0000-0003-4862-1503","position":22,"is_corresponding":false},{"id":69664,"name":"Roger D. Kouyos","orcid":"0000-0002-9220-8348","position":23,"is_corresponding":false},{"id":774617,"name":"Suraj Balakrishna","orcid":"0000-0001-9250-4078","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:10:21.947540Z","pmid":"36738248","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":[]}