{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:14:12Z","timestamp":1760228052397,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH)","doi-asserted-by":"publisher","award":["AI136618","19-75-10097","PTDC\/SAU-INF\/31990\/2017","PTDC\/SAU-PUB\/4018\/2021"],"award-info":[{"award-number":["AI136618","19-75-10097","PTDC\/SAU-INF\/31990\/2017","PTDC\/SAU-PUB\/4018\/2021"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Russian Science Foundation","award":["AI136618","19-75-10097","PTDC\/SAU-INF\/31990\/2017","PTDC\/SAU-PUB\/4018\/2021"],"award-info":[{"award-number":["AI136618","19-75-10097","PTDC\/SAU-INF\/31990\/2017","PTDC\/SAU-PUB\/4018\/2021"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["AI136618","19-75-10097","PTDC\/SAU-INF\/31990\/2017","PTDC\/SAU-PUB\/4018\/2021"],"award-info":[{"award-number":["AI136618","19-75-10097","PTDC\/SAU-INF\/31990\/2017","PTDC\/SAU-PUB\/4018\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Ritonavir-boosted atazanavir is an option for second-line therapy in low- and middle-income countries (LMICs). We analyzed publicly available HIV-1 protease sequences from previously PI-na\u00efve patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 published studies and 757 from datasets assembled for this analysis. A total of 63% of patients received boosted atazanavir. A total of 38% had non-subtype B viruses. A total of 264 (18%) sequences had a PI drug-resistance mutation (DRM) defined as having a Stanford HIV Drug Resistance Database mutation penalty score. Among sequences with a DRM, nine major DRMs had a prevalence &gt;5%: I50L (34%), M46I (33%), V82A (22%), L90M (19%), I54V (16%), N88S (10%), M46L (8%), V32I (6%), and I84V (6%). Common accessory DRMs were L33F (21%), Q58E (16%), K20T (14%), G73S (12%), L10F (10%), F53L (10%), K43T (9%), and L24I (6%). A novel nonpolymorphic mutation, L89T occurred in 8.4% of non-subtype B, but in only 0.4% of subtype B sequences. The 264 sequences included 3 (1.1%) interpreted as causing high-level, 14 (5.3%) as causing intermediate, and 27 (10.2%) as causing low-level darunavir resistance. Atazanavir selects for nine major and eight accessory DRMs, and one novel nonpolymorphic mutation occurring primarily in non-B sequences. Atazanavir-selected mutations confer low-levels of darunavir cross resistance. Clinical studies, however, are required to determine the optimal boosted PI to use for second-line and potentially later line therapy in LMICs.<\/jats:p>","DOI":"10.3390\/pathogens11050546","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T02:46:39Z","timestamp":1651805199000},"page":"546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Spectrum of Atazanavir-Selected Protease Inhibitor-Resistance Mutations"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1231-6542","authenticated-orcid":false,"given":"Soo-Yon","family":"Rhee","sequence":"first","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, CA 94305, USA"}]},{"given":"Michael","family":"Boehm","sequence":"additional","affiliation":[{"name":"Institute of Virology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50935 Cologne, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3723-7832","authenticated-orcid":false,"given":"Olga","family":"Tarasova","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Institute of Biomedical Chemistry, 119121 Moscow, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-0067","authenticated-orcid":false,"given":"Giulia","family":"Di Teodoro","sequence":"additional","affiliation":[{"name":"Department of Computer, Control and Management Engineering Antonio Ruberti, Sapienza University of Rome, 00185 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3903-5265","authenticated-orcid":false,"given":"Ana B.","family":"Abecasis","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, 1349-008 Lisboa, Portugal"}]},{"given":"Anders","family":"S\u00f6nnerborg","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institute, Huddinge, 14186 Stockholm, Sweden"}]},{"given":"Alexander J.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, CA 94305, USA"}]},{"given":"Dmitry","family":"Kireev","sequence":"additional","affiliation":[{"name":"Central Research Institute of Epidemiology, 111123 Moscow, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-6281","authenticated-orcid":false,"given":"Maurizio","family":"Zazzi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}]},{"name":"the EuResist Network Study Group","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-2643","authenticated-orcid":false,"given":"Robert W.","family":"Shafer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, CA 94305, USA"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","unstructured":"(2022, February 10). 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