{"doi":"10.1093/jac/dkac372","title":"High concordance in plasma and CSF HIV-1 drug resistance mutations despite high cases of CSF viral escape in individuals with HIV-associated cryptococcal meningitis in Botswana","abstract":"OBJECTIVES: We compared the patterns of HIV-1 drug resistance mutations between the CSF and plasma of individuals with HIV-associated cryptococcal meningitis. METHODS: This is a cross-sectional study of archived CSF and plasma samples collected from ART-exposed participants recruited in the Phase 3 AmBisome Therapy Induction Optimisation randomized controlled trial (ISRCTN72509687) conducted in Botswana between 2018 and 2021. HIV-1 RT and protease genes were genotyped using next-generation sequencing and HIV-1 drug resistance mutations were compared between the CSF and plasma compartments stratified by thresholds of ≥20% and <20%. RESULTS: Overall, 66.7% (16/24) of participants had at least one HIV-1 drug resistance mutation in the CSF and/or plasma. A total of 15/22 (68.2%) participants had HIV-1 drug resistance mutations at ≥20% threshold in the plasma and of those, 11 (73.3%) had been on ART longer than 6 months. HIV-1 drug resistance mutations were highly concordant between the CSF and plasma at ≥20% threshold despite a substantial number of individuals experiencing CSF viral escape and with only 54.5% with CSF WBC count ≥20 cells/mm3. Minority HIV-1 drug resistance mutations were detected in 20.8% (5/24) of participants. There were no mutations in the CSF that were not detected in the plasma. CONCLUSIONS: There was high concordance in HIV-1 drug resistance mutations in the CSF and plasma, suggesting intercompartmental mixing and possibly a lack of compartmentalization. Some individuals harboured minority HIV-1 drug resistance mutations, demonstrating the need to employ more sensitive genotyping methods such as next-generation sequencing for the detection of low-abundance mutations.","journal":"Journal of Antimicrobial Chemotherapy","year":2022,"id":287806,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":425983,"name":"Sikhulile Moyo","orcid":"0000-0003-3821-4592","position":1,"is_corresponding":false},{"id":425978,"name":"Wonderful T. Choga","orcid":"0000-0001-7606-0569","position":2,"is_corresponding":false},{"id":402527,"name":"Kwana Lechiile","orcid":"0000-0001-6691-1905","position":3,"is_corresponding":false},{"id":402525,"name":"Tshepo Leeme","orcid":"0000-0002-6153-4693","position":4,"is_corresponding":false},{"id":514552,"name":"David S. Lawrence","orcid":"0000-0002-5439-4039","position":5,"is_corresponding":false},{"id":443983,"name":"Ishmael Kasvosve","orcid":"0000-0002-2046-545X","position":6,"is_corresponding":false},{"id":425980,"name":"Rosemary Musonda","orcid":"0009-0009-9937-6908","position":7,"is_corresponding":false},{"id":393321,"name":"Mosepele Mosepele","orcid":"0000-0002-6051-0999","position":8,"is_corresponding":false},{"id":410998,"name":"Thomas S. Harrison","orcid":"0000-0003-3619-4348","position":9,"is_corresponding":false},{"id":402528,"name":"Joseph N Jarvis","orcid":"0000-0003-1459-5554","position":10,"is_corresponding":false},{"id":425985,"name":"Simani Gaseitsiwe","orcid":"0000-0002-7089-3735","position":11,"is_corresponding":false},{"id":514548,"name":"Nametso Kelentse","orcid":"0000-0003-2433-2416","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-19T00:30:01.051685Z","pmid":"36322466","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":[]}