{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:52:33Z","timestamp":1793757153257,"version":"4.6.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Dolutegravir (DTG) is the anchor drug of the first-line agent for HIV treatment globally, including low- and middle-income countries. Although clinical trials report low rates of integrase inhibitor resistance, real-world data from sub-Saharan Africa suggest a different scenario. We aimed to assess the prevalence and patterns of DTG resistance in Mozambique, building on prior preliminary findings with an expanded cohort and extended observation period.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We conducted a retrospective observational study in five DREAM centers in Mozambique. HIV-positive individuals on DTG-based antiretroviral therapy (ART) with confirmed virological failure (HIV RNA\u2009&gt;\u20091000 copies\/mL) between July 2022 and December 2024 were included. Participants underwent genotypic resistance testing after six months of enhanced adherence support. Resistance mutations were identified via Sanger sequencing and interpreted using the Stanford HIV Drug Resistance Database.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of 28 individual tested, 13 (46.4%) exhibited DTG resistance (12\/13 with intermediate or high-level resistance); 92.3% harboured HIV-1 subtype C. Frequently observed mutations included G118R (43.8%), E138K (43.8%), L74M (31.3%), and R263K (25.0%), often in combination. All DTG-resistant individuals who underwent testing for other drug classes (<jats:italic>n<\/jats:italic>\u2009=\u20099) also showed co-resistance to NRTIs and\/or NNRTIs. Notably, high-level resistance emerged also in 6 failing participants having shifted to DTG while virologically suppressed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This study reports the presence of DTG resistance and multiclass failure in Mozambique, suggesting potential limitations of current strategies. Sentinel surveillance and expanded access to resistance testing are important to preserve the efficacy of DTG-based regimens and inform future deployment of long-acting therapies in sub-Saharan Africa.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12879-025-11639-2","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T19:23:45Z","timestamp":1759173825000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["HIV Dolutegravir resistance and multiclass failure in Mozambique: findings from a real-world cohort"],"prefix":"10.1186","volume":"25","author":[{"given":"Fausto","family":"Ciccacci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Doro Altan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noorjehan","family":"Majid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Orlando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elton","family":"Uamusse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Rafael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zita","family":"Sidumo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Germano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Guidotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Federico","family":"Perno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"11639_CR1","unstructured":"UNAIDS. Global HIV & AIDS statistics \u2014 Fact sheet 2024. https:\/\/www.unaids.org\/en\/resources\/fact-sheet (Accessed 10 Oct 2024)."},{"key":"11639_CR2","unstructured":"World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines. Supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. 2018."},{"key":"11639_CR3","unstructured":"World Health Organization. HIV drug resistance: brief report 2024. 2024."},{"key":"11639_CR4","unstructured":"Minist\u00e9rio da Sa\u00fade, Direc\u00e7\u00e3o Nacional de Sa\u00fade P\u00fablica, PNC ITS-HIV\/SIDA. Normas Cl\u00ednicas Actualizadas para o seguimento do paciente HIV positivo. 2019."},{"key":"11639_CR5","doi-asserted-by":"publisher","first-page":"1253661","DOI":"10.3389\/fviro.2023.1253661","volume":"3","author":"D Kamori","year":"2023","unstructured":"Kamori D, Barabona G. Dolutegravir resistance in sub-Saharan Africa: should resource-limited settings be concerned for future treatment? Front Virol. 2023;3:1253661. https:\/\/doi.org\/10.3389\/fviro.2023.1253661.","journal-title":"Front Virol"},{"key":"11639_CR6","doi-asserted-by":"publisher","first-page":"e733","DOI":"10.1016\/S2352-3018(23)00228-X","volume":"10","author":"T Loosli","year":"2023","unstructured":"Loosli T, Hossmann S, Ingle SM, Okhai H, Kusejko K, Mouton J, et al. HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis. Lancet HIV. 2023;10:e733\u201341. https:\/\/doi.org\/10.1016\/S2352-3018(23)00228-X.","journal-title":"Lancet HIV"},{"key":"11639_CR7","doi-asserted-by":"publisher","unstructured":"Semengue ENJ, Santoro MM, Ndze VN, Ka\u2019e AC, Bouba Y, Nka AD, et al. 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 2022. https:\/\/doi.org\/10.1371\/journal.pgph.0000826.","DOI":"10.1371\/journal.pgph.0000826"},{"key":"11639_CR8","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/256982","volume":"2012","author":"MA Wainberg","year":"2012","unstructured":"Wainberg MA, Brenner BG. The impact of HIV genetic polymorphisms and subtype differences on the occurrence of resistance to antiretroviral drugs. Mol Biol Int. 2012;2012:256982. https:\/\/doi.org\/10.1155\/2012\/256982.","journal-title":"Mol Biol Int"},{"key":"11639_CR9","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12981-025-00708-w","volume":"22","author":"AM Doro Altan","year":"2025","unstructured":"Doro Altan AM, Majid N, Orlando S, Uamusse E, Rafael M, Sidumo Z, et al. Brief communication: virological outcomes and dolutegravir resistance mutations in HIV-infected patients: a multicenter retrospective cohort study in Mozambique. AIDS Res Ther. 2025;22:8. https:\/\/doi.org\/10.1186\/s12981-025-00708-w.","journal-title":"AIDS Res Ther"},{"key":"11639_CR10","doi-asserted-by":"publisher","unstructured":"Altan AMD, Taafo F, Fopa F, Buonomo E, Marazzi MC, Nielsen-Saines K, et al. An assessment of option B implementation for the prevention of mother to child transmission in Dschang, Cameroon: results from the DREAM (Drug Resource Enhancement against AIDS and Malnutrition) cohort. Pan Afr Med J. 2016;23. https:\/\/doi.org\/10.11604\/pamj.2016.23.72.7958.","DOI":"10.11604\/pamj.2016.23.72.7958"},{"key":"11639_CR11","doi-asserted-by":"publisher","DOI":"10.1515\/ijamh-2022-0107","author":"F Ciccacci","year":"2023","unstructured":"Ciccacci F, Ismael F, Chume V, Ruth L, Mbula P, Orlando S, et al. Enhancing retention in care in HIV-infected adolescents during COVID-19 in Mozambique: results from the DREAM program. Int J Adolesc Med Health. 2023. https:\/\/doi.org\/10.1515\/ijamh-2022-0107.","journal-title":"Int J Adolesc Med Health"},{"key":"11639_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0242068","volume":"15","author":"F Ciccacci","year":"2020","unstructured":"Ciccacci F, Lucaroni F, Latagliata R, Morciano L, Mondlane E, Balama M, et al. Hematologic alterations and early mortality in a cohort of HIV positive African patients. PLoS ONE. 2020;15:e0242068. https:\/\/doi.org\/10.1371\/journal.pone.0242068.","journal-title":"PLoS ONE"},{"key":"11639_CR13","doi-asserted-by":"publisher","unstructured":"Magnano San Lio M, Mancinelli S, Palombi L, Buonomo E, Altan AD, Germano P, et al. The DREAM model\u2019s effectiveness in health promotion of AIDS patients in Africa. Health Promot Int. 2009;24:6\u201315. https:\/\/doi.org\/10.1093\/heapro\/dan043.","DOI":"10.1093\/heapro\/dan043"},{"key":"11639_CR14","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S1473-3099(19)30036-2","volume":"19","author":"M Aboud","year":"2019","unstructured":"Aboud M, Kaplan R, Lombaard J, Zhang F, Hidalgo JA, Mamedova E, et al. Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. Lancet Infect Dis. 2019;19:253\u201364. https:\/\/doi.org\/10.1016\/S1473-3099(19)30036-2.","journal-title":"Lancet Infect Dis"},{"key":"11639_CR15","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1056\/NEJMoa210160","volume":"385","author":"NI Paton","year":"2021","unstructured":"Paton NI, Musaazi J, Kityo C, Walimbwa S, Hoppe A, Balyegisawa A, et al. Dolutegravir or darunavir in combination with zidovudine or tenofovir to treat HIV. N Engl J Med. 2021;385:330\u201341. https:\/\/doi.org\/10.1056\/NEJMoa210160.","journal-title":"N Engl J Med"},{"key":"11639_CR16","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3390\/pathogens14010048","volume":"14","author":"N Ismael","year":"2025","unstructured":"Ismael N, Hussein C, Magul C, Inguane H, Couto A, Nhangave A, et al. HIV drug resistance profile in clients experiencing treatment failure after the transition to a Dolutegravir-based first-line antiretroviral treatment regimen in Mozambique. Pathogens. 2025;14:48. https:\/\/doi.org\/10.3390\/pathogens14010048.","journal-title":"Pathogens"},{"key":"11639_CR17","doi-asserted-by":"publisher","unstructured":"Ruano M, Flores A, Couto A, Gaspar I, Yerly S, Zamudio AGG, et al. Dolutegravir Resistance in Mozambique: Insights from a Programmatic HIV Resistance Testing Intervention in a Highly ART Experienced Cohort 2025. https:\/\/doi.org\/10.20944\/preprints202504.1432.v1.","DOI":"10.20944\/preprints202504.1432.v1"},{"key":"11639_CR18","doi-asserted-by":"publisher","first-page":"e01386","DOI":"10.1128\/aac.01386-2","volume":"67","author":"MA Xiao","year":"2023","unstructured":"Xiao MA, Cleyle J, Yoo S, Forrest M, Krullaars Z, Pham HT, et al. The G118R plus R263K combination of integrase mutations associated with dolutegravir-based treatment failure reduces HIV-1 replicative capacity and integration. Antimicrob Agents Chemother. 2023;67:e01386-e1422. https:\/\/doi.org\/10.1128\/aac.01386-2.","journal-title":"Antimicrob Agents Chemother"},{"key":"11639_CR19","doi-asserted-by":"publisher","first-page":"3163","DOI":"10.1128\/jvi.03353-14","volume":"89","author":"PK Quashie","year":"2015","unstructured":"Quashie PK, Oliviera M, Veres T, Osman N, Han Y-S, Hassounah S, et al. Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. J Virol. 2015;89:3163\u201375. https:\/\/doi.org\/10.1128\/jvi.03353-14.","journal-title":"J Virol"},{"key":"11639_CR20","doi-asserted-by":"publisher","unstructured":"Fourie N, Rees K, Mali D, Mugisa B, Davies N. Dolutegravir resistance in three pregnant and breastfeeding women in South Africa. South Afr J HIV Med 2023;24. https:\/\/doi.org\/10.4102\/sajhivmed.v24i1.1531.","DOI":"10.4102\/sajhivmed.v24i1.1531"},{"key":"11639_CR21","doi-asserted-by":"publisher","unstructured":"Mahomed K, Wallis CL, Dunn L, Maharaj S, Maartens G, Meintjes G. Case report: Emergence of dolutegravir resistance in a patient on second-line antiretroviral therapy. South Afr J HIV Med 2020;21. https:\/\/doi.org\/10.4102\/sajhivmed.v21i1.1062.","DOI":"10.4102\/sajhivmed.v21i1.1062"},{"key":"11639_CR22","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3390\/idr14040053","volume":"14","author":"H Mens","year":"2022","unstructured":"Mens H, Fjordside L, Fonager J, Gerstoft J. Emergence of the G118R pan-integrase resistance mutation as a result of low compliance to a dolutegravir-based cART. Infect Dis Rep. 2022;14:501\u20134. https:\/\/doi.org\/10.3390\/idr14040053.","journal-title":"Infect Dis Rep"},{"key":"11639_CR23","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1038\/s41591-023-02763-0","volume":"30","author":"J Fokam","year":"2024","unstructured":"Fokam J, Inzaule S, Colizzi V, Perno C-F, Kaseya J, Ndembi N. HIV drug resistance to integrase inhibitors in low-and middle-income countries. Nat Med. 2024;30:618\u20139. https:\/\/doi.org\/10.1038\/s41591-023-02763-0.","journal-title":"Nat Med"},{"key":"11639_CR24","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.3390\/v15091932","volume":"15","author":"K Tao","year":"2023","unstructured":"Tao K, Rhee S-Y, Chu C, Avalos A, Ahluwalia AK, Gupta RK, et al. Treatment emergent dolutegravir resistance mutations in individuals naive to HIV-1 integrase inhibitors: a rapid scoping review. Viruses. 2023;15:1932. https:\/\/doi.org\/10.3390\/v15091932.","journal-title":"Viruses"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-025-11639-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-025-11639-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-025-11639-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T19:23:46Z","timestamp":1759173826000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-025-11639-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,29]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["11639"],"URL":"https:\/\/doi.org\/10.1186\/s12879-025-11639-2","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,29]]},"assertion":[{"value":"22 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the National Bioethics Committee for Health of Mozambique (Ref: 430\/CNBS\/24, July 19, 2024). Given the retrospective nature of the study and the use of routinely collected anonymized data, the requirement for informed consent was waived.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1210"}}