{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:23:45Z","timestamp":1773415425367,"version":"3.50.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["IZ07Z0_160876\/1"],"award-info":[{"award-number":["IZ07Z0_160876\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["PCEFP3_181355"],"award-info":[{"award-number":["PCEFP3_181355"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["323530_177576"],"award-info":[{"award-number":["323530_177576"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011318","name":"Fondation Botnar","doi-asserted-by":"publisher","award":["REG-19-008"],"award-info":[{"award-number":["REG-19-008"]}],"id":[{"id":"10.13039\/501100011318","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>WHO guidelines on ART define the HIV-1 viral load (VL) threshold for treatment failure at 1000 copies\/mL. The Switch Either near Suppression Or THOusand (SESOTHO) trial, conducted in Lesotho from 2017 to 2020, found that patients with persistent viraemia below this threshold (100\u2013999 copies\/mL) benefit from switching to second-line ART. This pre-planned nested study assesses the prevalence of resistance-associated mutations (RAMs) in SESOTHO trial participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The SESOTHO trial [registered at ClinicalTrials.gov (NCT03088241)] enrolled 80 persons taking NNRTI-based first-line ART with low-level HIV-1 viraemia (100\u2013999 copies\/mL) and randomized them (1:1) to switch to a PI-based second-line regimen (switch) or continue on first-line therapy (control). We sequenced relevant regions of the viral pol gene using plasma samples obtained at enrolment and 36\u2009weeks. RAMs were classified with the Stanford HIV Drug Resistance Database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequencing data were obtained for 37\/80 (46%) participants at baseline and 26\/48 (54%) participants without viral suppression to &amp;lt;50 copies\/mL at 36\u2009weeks (21 control participants and 5 switch participants). At baseline, 31\/37 (84%) participants harboured high-level resistance to at least two drugs of their current regimen. At 36\u2009weeks, 17\/21 (81%) control participants harboured resistance to at least two drugs of their current regimen, while no PI-associated resistance was detected in the 5 switch participants with ongoing viraemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Among persons with low-level viraemia while taking NNRTI-based first-line ART enrolled in the SESOTHO trial, the majority harboured HIV-1 with RAMs that necessitate ART modification. These findings support lowering the VL threshold triggering a switch to second-line ART in future WHO guidelines.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkab025","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T20:13:09Z","timestamp":1611087189000},"page":"1294-1298","source":"Crossref","is-referenced-by-count":16,"title":["Extensive drug resistance during low-level HIV viraemia while taking NNRTI-based ART supports lowering the viral load threshold for regimen switch in resource-limited settings: a pre-planned analysis from the SESOTHO trial"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1874-6153","authenticated-orcid":false,"given":"Jennifer Anne","family":"Brown","sequence":"first","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"Molecular Virology, Department of Biomedicine, University of Basel, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1716-993X","authenticated-orcid":false,"given":"Alain","family":"Amstutz","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"},{"name":"Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bienvenu Lengo","family":"Nsakala","sequence":"additional","affiliation":[{"name":"SolidarMed, Partnerships for Health, Maseru, Lesotho"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Seeburg","sequence":"additional","affiliation":[{"name":"Molecular Virology, Department of Biomedicine, University of Basel, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8908-0953","authenticated-orcid":false,"given":"Fiona","family":"Vanobberghen","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-4543","authenticated-orcid":false,"given":"Josephine","family":"Muhairwe","sequence":"additional","affiliation":[{"name":"SolidarMed, Partnerships for Health, Maseru, Lesotho"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4945-6511","authenticated-orcid":false,"given":"Thomas","family":"Klimkait","sequence":"additional","affiliation":[{"name":"Molecular Virology, Department of Biomedicine, University of Basel, Basel, Switzerland"},{"name":"University of Basel, Basel, 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