{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T19:58:12Z","timestamp":1778702292014,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007301","name":"Harvard University Center for AIDS Research","doi-asserted-by":"publisher","award":["P30 AI060354"],"award-info":[{"award-number":["P30 AI060354"]}],"id":[{"id":"10.13039\/100007301","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fogarty International Center and National Institute of Mental Health, of the National Institutes of Health","award":["D43 TW010543"],"award-info":[{"award-number":["D43 TW010543"]}]},{"name":"Sub-Saharan African Network for TB\/HIV Research Excellence (SANTHE), a DELTAS Africa Initi-ative [grant # DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)\u2019s Alliance for Accelerating Excel","award":["Wellcome Trust [grant # 107752\/Z\/15\/Z]"],"award-info":[{"award-number":["Wellcome Trust [grant # 107752\/Z\/15\/Z]"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>There are limited real-world mutational and virological outcomes data of treatment-experienced persons diagnosed with HIV-1 subtype C (HIV-1 C) who are failing Integrase Strand Transfer Inhibitor-based regimens. Requisition forms sent for HIV-1 genotypic resistance testing (GRT) between May 2015 and September 2019 were reviewed and participants experiencing virologic failure while on dolutegravir (DTG) or raltegravir (RAL) cART at sampling recruited. Sanger sequencing of the HIV-1 Pol gene was performed from residual plasma samples and drug resistance mutational (DRM) analysis performed using the Stanford University HIV drug resistance database. 40 HIV-1C integrase sequences were generated from 34 individuals, 24 of whom were on DTG cART, three on RAL cART and seven on an unknown (DTG or RAL)-anchored cART at time of GRT. 11\/34 (32%) individuals had DRMs to DTG and other integrase inhibitors. 7\/11 (64%) patients had exposure to a RAL-based cART at the time of sampling. Out of the 11 individuals with DRMs, one (9%) had 2-class, 6 (55%) had 3-class, and 4 (36%) had 4-class multidrug-resistant HIV-1C. 7\/11 individuals (64%) are currently virologically suppressed. Of the four individuals not virologically suppressed, three had extensive DRMs involving 4-classes of ARV drugs and one individual has demised. Resistance to DTG occurs more often in patients exposed to RAL cART. Individuals with 4-class DRMs plus integrase T97 and E157Q mutations appear to have worse outcomes. There is a need for frequent VL monitoring and GRT amongst treatment-experienced HIV-1C diagnosed individuals.<\/jats:p>","DOI":"10.3390\/v13040594","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T10:24:33Z","timestamp":1617186273000},"page":"594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-2842","authenticated-orcid":false,"given":"Kaelo K.","family":"Seatla","sequence":"first","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"},{"name":"School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorcas","family":"Maruapula","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"},{"name":"School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7606-0569","authenticated-orcid":false,"given":"Wonderful T.","family":"Choga","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"},{"name":"Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tshenolo","family":"Ntsipe","sequence":"additional","affiliation":[{"name":"National Health Laboratory, Ministry of Health &amp; Wellness, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nametso","family":"Mathiba","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mompati","family":"Mogwele","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Kapanda","sequence":"additional","affiliation":[{"name":"Botswana Ministry of Health and Wellness, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bornapate","family":"Nkomo","sequence":"additional","affiliation":[{"name":"Botswana Ministry of Health and Wellness, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinah","family":"Ramaabya","sequence":"additional","affiliation":[{"name":"Botswana Ministry of Health and Wellness, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Makhema","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mompati","family":"Mmalane","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madisa","family":"Mine","sequence":"additional","affiliation":[{"name":"National Health Laboratory, Ministry of Health &amp; Wellness, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2046-545X","authenticated-orcid":false,"given":"Ishmael","family":"Kasvosve","sequence":"additional","affiliation":[{"name":"School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone 0000, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahin","family":"Lockman","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"},{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Immunology &amp; Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3821-4592","authenticated-orcid":false,"given":"Sikhulile","family":"Moyo","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"},{"name":"Department of Immunology &amp; Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simani","family":"Gaseitsiwe","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana"},{"name":"Department of Immunology &amp; Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.2147\/DDDT.S84850","article-title":"Dolutegravir\u2014A review of the pharmacology, efficacy, and safety in the treatment of HIV","volume":"9","author":"Kandel","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e127","DOI":"10.1016\/S2352-3018(15)00027-2","article-title":"Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study","volume":"2","author":"Molina","year":"2015","journal-title":"Lancet HIV"},{"key":"ref_3","unstructured":"EACS (2020, April 22). European AIDS Clinical Society (EACS) Guidelines Version 10.0. 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