{"doi":"10.1093/cid/ciac875","title":"Characterization of Viruses in Phase 3 and Phase 3b Trials (the Ring Study and the Dapivirine Ring Extended Access and Monitoring Trial) of the Dapivirine Vaginal Ring for Human Immunodeficiency Virus Type 1 Infection Risk Reduction","abstract":"BACKGROUND: The Ring Study demonstrated 35.1% human immunodeficiency virus type 1 (HIV-1) infection risk reduction among participants who used the Dapivirine vaginal ring-004 (DVR), whereas the Dapivirine Ring Extended Access and Monitoring (DREAM) trial, approximated a 62% risk reduction. The observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) and effects on viral susceptibility are described here. METHODS: Population-based genotyping on plasma samples collected longitudinally, and next-generation sequencing (NGS) and phenotypic susceptibility testing were done on plasma collected at seroconversion. Retrospective HIV-1 RNA testing was used to more accurately establish the time of infection. RESULTS: In the Ring Study, NNRTI RAMs were not observed in most viruses at seroconversion (population-based genotyping: DVR: 71 of 84, 84.5%; placebo: 50 of 58, 86.2%). However, more E138A was found in the DVR group (E138A DVR: 9 of 84, 10.7%; placebo: 2 of 58, 3.4%; P = .2, Fisher exact test). NGS detected 1 additional mutation in each group (DVR: G190A; placebo: G190A and G190E). Marginal dapivirine susceptibility reduction was found with NNRTI RAMs at seroconversion (geometric mean fold-change, range: DVR, 3.1, 1.3-5.1; placebo, 5.8, 0.9-120). NNRTI RAMs were not emergent between first detectable HIV-1 RNA and seroconversion when these visits differed (paired samples, mean ring use: DVR, n = 52, 35 days; placebo, n = 26, 31 days). After stopping DVR, 2 of 63 viruses had emergent G190G/A or K103K/N with V106V/M at final study visit. Resistance profiles from the DREAM trial were consistent with the Ring Study. CONCLUSIONS: DVR showed little potential for selection of NNRTI-resistant variants. CLINICAL TRIALS REGISTRATION: NCT01539226 and NCT02862171.","journal":"Clinical Infectious Diseases","year":2022,"id":290581,"datarank":0.2850624506851407,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.04364676382002563,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.04364676382002563,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02862171","NCT01539226"]},"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":972999,"name":"Charles Craig","orcid":"0000-0003-3276-9925","position":1,"is_corresponding":false},{"id":973000,"name":"Elna van der Ryst","orcid":"0000-0002-9193-1825","position":2,"is_corresponding":false},{"id":306138,"name":"Ben Van Baelen","orcid":null,"position":3,"is_corresponding":false},{"id":783539,"name":"Jeremy Nuttall","orcid":"0000-0003-1346-3357","position":4,"is_corresponding":false},{"id":973481,"name":"Neliëtte van Niekerk","orcid":null,"position":5,"is_corresponding":false},{"id":258969,"name":"John W. Mellors","orcid":"0000-0002-3737-9742","position":6,"is_corresponding":false},{"id":629745,"name":"Urvi M. Parikh","orcid":"0000-0002-4016-0629","position":7,"is_corresponding":false},{"id":472118,"name":"Carole L. Wallis","orcid":"0000-0001-8408-8772","position":8,"is_corresponding":false},{"id":973482,"name":"for the Ring Study and the DREAM Trial Study Teams","orcid":null,"position":9,"is_corresponding":false},{"id":973480,"name":"John Steytler","orcid":null,"position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-19T00:30:30.639224Z","pmid":"36345569","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":[]}