{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T20:15:10Z","timestamp":1788552910524,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. President\u2019s Emergency Plan for AIDS Relief (PEPFAR)","award":["#NU2GGH001945"],"award-info":[{"award-number":["#NU2GGH001945"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Real-world data on HIV drug resistance (HIVDR) after transitioning to tenofovir disoproxil fumarate\/lamivudine\/dolutegravir (TLD) are limited. We assessed HIVDR rates and patterns in clients with virological failure (VF) after switching from an NNRTI-based regimen to TLD. A cross-sectional study was conducted in Gaza, Mozambique (August 2021\u2013February 2022), including adults on first-line ART for \u226512 months who transitioned to TLD and had unsuppressed viral load (VL) \u2265 1000 copies\/mL six months post-transition. After three adherence counseling sessions, participants with VF underwent genotyping for drug resistance mutations (DRMs) using the Stanford HIVdb Program. Of 717 participants (median age 39.2 years, 70.7% female), 217 (30.2%) had VF, 193 (88.9%) underwent genotyping, with 183 (94.8%) successfully genotyped. Intermediate\u2013high dolutegravir (DTG) resistance was found in 19.6% (36\/183). Unsuppressed VL before DTG transition was independently associated with VF (aOR: 2.14). Resistance patterns included 33.3% (12\/36; 95% CI: 14.6\u201346.3) to all three TLD drugs, 55.6% (20\/36; 95% CI: 39.3\u201371.9) to DTG and 3TC, and 11% (4\/36; 95% CI: 0.8\u201321.3) to DTG only. Major drug resistance mutations to DTG included G118R (9.3%), R263K (6.6%), and Q148H\/R\/K (4.4%). This study highlights the need to consider virologic status before transitioning PLHIV to TLD and suggests that adherence counseling may not prevent resistance in those with unknown or prior VF.<\/jats:p>","DOI":"10.3390\/pathogens14010048","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T07:00:47Z","timestamp":1736406047000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["HIV Drug Resistance Profile in Clients Experiencing Treatment Failure After the Transition to a Dolutegravir-Based First-Line Antiretroviral Treatment Regimen in Mozambique"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1793-9471","authenticated-orcid":false,"given":"Nalia","family":"Ismael","sequence":"first","affiliation":[{"name":"Instituto Nacional de Sa\u00fade, Estrada Nacional N1, Marracuene 3943, Mozambique"},{"name":"Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cidia","family":"Hussein","sequence":"additional","affiliation":[{"name":"Elizabeth Glaser Pediatric AIDS Foundation, Avenida Paulo Samuel KanKhomba, 280 Bairro da Sommerschield, Maputo 20005, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1537-2137","authenticated-orcid":false,"given":"Cacildo","family":"Magul","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Sa\u00fade, Estrada Nacional N1, Marracuene 3943, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humberto","family":"Inguane","sequence":"additional","affiliation":[{"name":"Elizabeth Glaser Pediatric AIDS Foundation, Avenida Paulo Samuel KanKhomba, 280 Bairro da Sommerschield, Maputo 20005, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleny","family":"Couto","sequence":"additional","affiliation":[{"name":"National HIV and STI Control Program, Ministry of Health, Salvador Allende 1008, Maputo 1101, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amancio","family":"Nhangave","sequence":"additional","affiliation":[{"name":"Operational Research Unit, Gaza Provincial Health Directorate, Rua do Hospital Provincial, 33 Bairro 13, Cidade de Xai-Xai 1200, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Muteerwa","sequence":"additional","affiliation":[{"name":"Division of Global HIV & TB, U.S. Centers for Diseases Control and Prevention, Avenida Marginal 5467, Maputo 1101, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6017-3082","authenticated-orcid":false,"given":"Mahoudo","family":"Bonou","sequence":"additional","affiliation":[{"name":"Elizabeth Glaser Pediatric AIDS Foundation, Avenida Paulo Samuel KanKhomba, 280 Bairro da Sommerschield, Maputo 20005, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4803-1611","authenticated-orcid":false,"given":"Artur","family":"Ramos","sequence":"additional","affiliation":[{"name":"Division of Global HIV & TB, U.S. Centers for Diseases Control and Prevention, Avenida Marginal 5467, Maputo 1101, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Wesley","family":"Young","sequence":"additional","affiliation":[{"name":"Division of Global HIV & TB, U.S. Centers for Diseases Control and Prevention, Avenida Marginal 5467, Maputo 1101, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Chilundo","sequence":"additional","affiliation":[{"name":"Division of Global HIV & TB, U.S. Centers for Diseases Control and Prevention, Avenida Marginal 5467, Maputo 1101, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhoderick","family":"Machekano","sequence":"additional","affiliation":[{"name":"Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC 20005, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-0408","authenticated-orcid":false,"given":"Lauren","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC 20005, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"da Silva","sequence":"additional","affiliation":[{"name":"Division of Global HIV & TB, U.S. Centers for Diseases Control and Prevention, Atlanta, GA 30333, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC 20005, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023, January 08). Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring Recommendations for a Public Health Approach. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240031593."},{"key":"ref_2","unstructured":"Ministry of Health of Mozambique (2023, January 08). Relat\u00f3rio Anual HIV, Available online: https:\/\/www.misau.gov.mz\/index.php\/relatorios-anuais#."},{"key":"ref_3","first-page":"203","article-title":"Transmitted Drug Resistance Against Integrase Strand Transfer Inhibitors in Iranian HIV-Infected Na\u00efve Patients","volume":"15","author":"Hashempour","year":"2023","journal-title":"Avicenna J. Med. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1089\/aid.2012.0058","article-title":"Genetic diversity and naturally polymorphisms in HIV type 1 integrase isolates from Maputo, Mozambique: Implications for integrase inhibitors","volume":"28","author":"Oliveira","year":"2012","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1093\/jac\/dkac134","article-title":"HIV-1 non-B resistance mutations and natural polymorphisms to integrase strand transfer inhibitors in recently diagnosed patients in Gabon, Central Africa","volume":"77","author":"Bignoumba","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1093\/jac\/dkw071","article-title":"Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors","volume":"71","author":"Brenner","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e733","DOI":"10.1016\/S2352-3018(23)00228-X","article-title":"HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: A collaborative cohort analysis","volume":"10","author":"Loosli","year":"2023","journal-title":"Lancet HIV"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.meegid.2016.06.047","article-title":"Differences among HIV-1 subtypes in drug resistance against integrase inhibitors","volume":"46","author":"Han","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Rhee, S.-Y., Liu, T.F., Kiuchi, M., Zioni, R., Gifford, R.J., Holmes, S.P., and Shafer, R.W. (2008). Natural variation of HIV-1 group M integrase: Implications for a new class of antiretroviral inhibitors. Retrovirology, 5.","DOI":"10.1186\/1742-4690-5-74"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jviromet.2010.12.006","article-title":"Abbott RealTime HIV-1 m2000rt viral load testing: Manual extraction versus the automated m2000sp extraction","volume":"172","author":"Scott","year":"2011","journal-title":"J. Virol. Methods"},{"key":"ref_11","unstructured":"Roche Diagnostics (2023, January 08). COBAS\u00ae AmpliPrep\/COBAS\u00ae TaqMan\u00ae HIV-1 Test, v2.0. Available online: https:\/\/www.aphl.org\/programs\/infectious_disease\/Documents\/IFU-COBASAmpliPrepCOBASTaqMan_HIV-1_Testversion2.pdf."},{"key":"ref_12","unstructured":"Qiagen (2023, January 08). QIAquick PCR Purification Kit. Available online: https:\/\/www.qiagen.com\/us\/products\/discovery-and-translational-research\/dna-rna-purification\/dna-purification\/dna-clean-up\/qiaquick-pcr-purification-kit."},{"key":"ref_13","unstructured":"ThermoFisher Scientific (2023, January 08). HIV-1 Genotyping Kit with Integrase. Available online: https:\/\/www.thermofisher.com\/order\/catalog\/product\/A55120."},{"key":"ref_14","unstructured":"ThermoFisher Scientific (2023, January 08). HIV-1 Drug Resistance Testing. Available online: https:\/\/www.thermofisher.com\/us\/en\/home\/life-science\/sequencing\/sanger-sequencing\/applications\/genotyping-hiv-detect-drug-resistance.html."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.meegid.2013.04.032","article-title":"Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: Performance evaluation of the new REGA version 3 and seven other tools","volume":"19","author":"Faria","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sebasti\u00e3o, C.S., Abecasis, A.B., Jandondo, D., Sebasti\u00e3o, J.M.K., Vig\u00e1rio, J., Comandante, F., Pingarilho, M., Pocongo, B., Cassinela, E., and Gon\u00e7alves, F. (2024). HIV-1 diversity and pre-treatment drug resistance in the era of integrase inhibitor among newly diagnosed ART-na\u00efve adult patients in Luanda, Angola. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-66905-1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1097\/QAD.0000000000002854","article-title":"Pre-treatment integrase inhibitor resistance is uncommon in antiretroviral therapy-naive individuals with HIV-1 subtype A1 and D infections in Uganda","volume":"35","author":"McCluskey","year":"2021","journal-title":"AIDS"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kouamou, V., Washaya, T., Ndhlovu, C.E., and Manasa, J. (2023). Low Prevalence of Pre-Treatment and Acquired Drug Resistance to Dolutegravir among Treatment Na\u00efve Individuals Initiating on Tenofovir, Lamivudine and Dolutegravir in Zimbabwe. Viruses, 15.","DOI":"10.3390\/v15091882"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Siedner, M.J., Moorhouse, M.A., Simmons, B., De Oliveira, T., Lessells, R., Giandhari, J., Kemp, S.A., Chimukangara, B., Akpomiemie, G., and Serenata, C.M. (2020). Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase. Nat. Commun., 11.","DOI":"10.1038\/s41467-020-19801-x"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ismael, N., Gemusse, H., Mahumane, I., Laurindo, O., Magul, C., Baxter, C., Wilkinson, E., Hofstra, L.M., Wagar, N., and Bila, D. (2024). HIV-1 pretreatment and acquired antiretroviral drug resistance before tenofovir\/lamivudine\/dolutegravir (TLD) roll-out in Mozambique. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09579-4"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1093\/cid\/ciae185","article-title":"Emergence of Acquired Dolutegravir Resistance in Treatment-experienced People With HIV in Lesotho","volume":"79","author":"Tschumi","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e622","DOI":"10.1093\/infdis\/jiae260","article-title":"Population Effeciveness of Dolutegravir Implementation in Uganda: A Prospective Observational Cohort Study (DISCO), 48-Week Results","volume":"230","author":"McCluskey","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e381","DOI":"10.1016\/S2352-3018(22)00092-3","article-title":"Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): Week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial","volume":"9","author":"Paton","year":"2022","journal-title":"Lancet HIV"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"ofae321","DOI":"10.1093\/ofid\/ofae321","article-title":"Dolutegravir Resistance in African Programmatic Settings Among Patients With Failure of Dolutegravir-based ART","volume":"11","author":"Murphy","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18640","DOI":"10.7448\/IAS.16.3.18640","article-title":"Impact of HIV-related stigma on treatment adherence: Systematic review and meta-synthesis","volume":"16","author":"Katz","year":"2013","journal-title":"J. Int. AIDS Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e620","DOI":"10.1016\/S2214-109X(21)00025-5","article-title":"The potential role of long-acting injectable cabotegravir-rilpivirine in the treatment of HIV in sub-Saharan Africa: A modelling analysis","volume":"9","author":"Phillips","year":"2021","journal-title":"Lancet Glob. Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S1473-3099(24)00289-5","article-title":"Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): Week 48 results from a randomised, multicentre, open-label, non-inferiority trial","volume":"24","author":"Kityo","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.antiviral.2009.10.003","article-title":"Fifteen years of HIV Protease Inhibitors: Raising the barrier to resistance","volume":"85","author":"Wensing","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Semengue, E.N.J., Santoro, M.M., Ndze, V.N., Dambaya, B., Takou, D., Teto, G., Nka, A.D., Fabeni, L., Wiyeh, A., and Ceccherini-Silberstein, F. (2022). HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis. PLoS Glob. Public Health, 2.","DOI":"10.1371\/journal.pgph.0000826"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1128\/JVI.03353-14","article-title":"Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase","volume":"89","author":"Quashie","year":"2015","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Seatla, K.K., Maruapula, D., Choga, W.T., Ntsipe, T., Mathiba, N., Mogwele, M., Kapanda, M., Nkomo, B., Ramaabya, D., and Makhema, J. (2021). HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. Viruses, 13.","DOI":"10.3390\/v13040594"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9210","DOI":"10.1128\/JVI.01164-10","article-title":"Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor","volume":"84","author":"Sloan","year":"2010","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1093\/jac\/dkz256","article-title":"A systematic review of the genetic mechanisms of dolutegravir resistance","volume":"74","author":"Rhee","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1128\/JCM.37.7.2291-2296.1999","article-title":"Worldwide evaluation of DNA sequencing approaches for identification of drug resistance mutations in the human immunodeficiency virus type 1 reverse transcriptase","volume":"37","author":"Schuurman","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.00922-17","article-title":"Mutations Located outside the Integrase Gene Can Confer Resistance to HIV-1 Integrase Strand Transfer Inhibitors","volume":"8","author":"Malet","year":"2017","journal-title":"mBio"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1093\/jac\/dkz377","article-title":"Variability of the HIV-1 3\u2032 polypurine tract (3\u2032PPT) region and implication in integrase inhibitor resistance","volume":"74","author":"Malet","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_37","unstructured":"Ministry of Health of Mozambique (2023, January 08). Mozambique Population-Based HIV Impact Assessment 2021 (INSIDA 2021), Available online: https:\/\/phia.icap.columbia.edu\/mozambique-final-report-2021-en-port\/."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/1\/48\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:25:26Z","timestamp":1759919126000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/1\/48"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["pathogens14010048"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14010048","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]}}}