{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T12:23:05Z","timestamp":1781871785904,"version":"3.54.5"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T00:00:00Z","timestamp":1610755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>HIV-1 subtype CRF01_AE is the second most predominant strain in Bulgaria, yet little is known about the molecular epidemiology of its origin and transmissibility. We used a phylodynamics approach to better understand this sub-epidemic by analyzing 270 HIV-1 polymerase (pol) sequences collected from persons diagnosed with HIV\/AIDS between 1995 and 2019. Using network analyses at a 1.5% genetic distance threshold (d), we found a large 154-member outbreak cluster composed mostly of persons who inject drugs (PWID) that were predominantly men. At d = 0.5%, which was used to identify more recent transmission, the large cluster dissociated into three clusters of 18, 12, and 7 members, respectively, five dyads, and 107 singletons. Phylogenetic analysis of the Bulgarian sequences with publicly available global sequences showed that CRF01_AE likely originated from multiple Asian countries, with Vietnam as the likely source of the outbreak cluster between 1988 and 1990. Our findings indicate that CRF01_AE was introduced into Bulgaria multiple times since 1988, and infections then rapidly spread among PWID locally with bridging to other risk groups and countries. CRF01_AE continues to spread in Bulgaria as evidenced by the more recent large clusters identified at d = 0.5%, highlighting the importance of public health prevention efforts in the PWID communities.<\/jats:p>","DOI":"10.3390\/v13010116","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T02:36:05Z","timestamp":1611196565000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-1124","authenticated-orcid":false,"given":"Ivailo","family":"Alexiev","sequence":"first","affiliation":[{"name":"National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9535-4420","authenticated-orcid":false,"given":"Ellsworth M.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-1831","authenticated-orcid":false,"given":"Sergey","family":"Knyazev","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA"},{"name":"Department of Computer Science, Georgia State University, Atlanta, GA 30303, USA"},{"name":"Oak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyubomira","family":"Grigorova","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7711-6798","authenticated-orcid":false,"given":"Reneta","family":"Dimitrova","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Partsuneva","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gancheva","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asya","family":"Kostadinova","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0636-5222","authenticated-orcid":false,"given":"Carole","family":"Seguin-Devaux","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, Luxembourg Institute of Health, 4354 Luxembourg, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivaylo","family":"Elenkov","sequence":"additional","affiliation":[{"name":"Specialized Hospital for Active Treatment of Infectious &amp; Parasitic Diseases, 1606 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Yancheva","sequence":"additional","affiliation":[{"name":"Specialized Hospital for Active Treatment of Infectious &amp; Parasitic Diseases, 1606 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4591-8731","authenticated-orcid":false,"given":"William M.","family":"Switzer","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1093\/molbev\/msy089","article-title":"The Puzzle of HIV Neutral and Selective Evolution","volume":"35","author":"Leitner","year":"2018","journal-title":"Mol. 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