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Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 gag and 488 pol HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections. Putative transmission clusters, with a 1.5% pairwise genetic distance threshold, were inferred from maximum likelihood phylogenies; clusters arising after the start of SEARCH were identified with Bayesian time-calibrated phylogenies. Our phylodynamic approach identified nine clusters arising after the SEARCH start date: eight pairs and one triplet, representing mostly opposite-gender linked (6\/9), within-community transmissions (7\/9). Two clusters contained individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, both linked to intervention communities. The identification of SEARCH-incident, within-community transmissions reveals the role of unsuppressed individuals in sustaining the epidemic in both arms of a UTT trial setting. The presence of transmitted NNRTI resistance, implying treatment failure to the efavirenz-based antiretroviral therapy (ART) used during SEARCH, highlights the need to improve delivery and adherence to up-to-date ART recommendations, to halt HIV-1 transmission.<\/jats:p>","DOI":"10.3390\/v14081673","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T23:49:27Z","timestamp":1659397767000},"page":"1673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-6608","authenticated-orcid":false,"given":"Emma","family":"Pujol-Hodge","sequence":"first","affiliation":[{"name":"Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4626-6448","authenticated-orcid":false,"given":"Jesus","family":"Salazar-Gonzalez","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC)\/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9675-4234","authenticated-orcid":false,"given":"Deogratius","family":"Ssemwanga","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC)\/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe P.O. Box 49, Uganda"},{"name":"Uganda Virus Research Institute, Entebbe P.O. 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Box 54840-00200, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9500-1644","authenticated-orcid":false,"given":"Heather","family":"Grant","sequence":"additional","affiliation":[{"name":"Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teri","family":"Liegler","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5250-0558","authenticated-orcid":false,"given":"Katherine","family":"Atkins","sequence":"additional","affiliation":[{"name":"Usher Institute, University of Edinburgh, Edinburgh EH8 9AG, UK"},{"name":"Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, LSHTM, London WC1E 7HT, UK"},{"name":"Centre for Mathematical Modelling of Infectious Diseases, LSHTM, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pontiano","family":"Kaleebu","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC)\/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe P.O. Box 49, Uganda"},{"name":"Uganda Virus Research Institute, Entebbe P.O. Box 49, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9106-4234","authenticated-orcid":false,"given":"Moses","family":"Kamya","sequence":"additional","affiliation":[{"name":"School of Medicine, Makerere University, Kampala P.O. Box 7072, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Petersen","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Havlir","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Leigh Brown","sequence":"additional","affiliation":[{"name":"Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1056\/NEJMoa1809866","article-title":"HIV Testing and Treatment with the Use of a Community Health Approach in Rural Africa","volume":"381","author":"Havlir","year":"2019","journal-title":"N. 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