{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T19:22:39Z","timestamp":1772306559834,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>People living with HIV (PLHIV) who fail first-line ART have a higher risk of failing subsequent ART. We examined viral suppression (VS) among adolescents and youths (AY) failing PI ART in Tanzania.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a retrospective study nested within a national third-line cohort of PLHIV. We analysed data of 147 AY (aged 10\u201324\u2005years) with failure of PI-based ART between 2020 and 2022 who were followed for 12\u2005months to assess for VS. Descriptive statistics were summarized by demographics and clinical characteristics, and we used logistic regression to assess factors associated with virological failure (VF) and drug resistance mutations (DRMs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>More than 40% of 147 participants had HIV subtype A, 52% (76\/147) harboured major PI DRMs and 35% had NRTI mutations. A PI regimen at ART initiation was associated with a major PI DRM adjusted relative risk (aRR) of 1.66 (95% CI: 1.13\u20132.44; P\u200a=\u200a0.010). Among participants with major PI DRMs, 12.2% had intermediate to high levels of resistance to lopinavir and atazanavir, and 2.1% to darunavir, respectively. V82A was the most frequent PI DRM; NRTI mutations included thymidine analogue mutations and absent K65R. VS occurred in 65% of AY who had PI DRMs compared with 45% of those without DRMs; this difference was not statistically significant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>More than half of AY who had PI DRMs had a higher proportion of early VS (65%) compared with those without DRMs (45%). Optimal viral load monitoring, adherence intensification and routine drug resistance testing are key strategies to improve VS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaf125","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T09:05:09Z","timestamp":1746176709000},"page":"1694-1701","source":"Crossref","is-referenced-by-count":1,"title":["Viral suppression after failure of PI-based ART among adolescents and youths with and without drug resistance mutations: a longitudinal analysis in Tanzania"],"prefix":"10.1093","volume":"80","author":[{"given":"Joan","family":"Rugemalila","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences , Dar es Salaam ,","place":["Tanzania"]},{"name":"Department of Internal Medicine, Muhimbili National Hospital , Dar es Salaam ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Ndege","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Ifakara Health Institute , Morogoro ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Kunambi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Muhimbili University of Health and Allied Sciences , Dar es Salaam ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siraji","family":"Shabani","sequence":"additional","affiliation":[{"name":"Department of Strategic Information, National AIDs Control Program , Dodoma ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veryeh","family":"Sambu","sequence":"additional","affiliation":[{"name":"Department of Strategic Information, National AIDs Control Program , Dodoma ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anath","family":"Rwebemberwa","sequence":"additional","affiliation":[{"name":"Department of Strategic Information, National AIDs Control Program , Dodoma ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Kalluvya","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Catholic University of Health and Allied Sciences , Mwanza ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Sunguya","sequence":"additional","affiliation":[{"name":"Department of Community Health, Muhimbili University of Health and Allied Sciences , Dar es Salaam ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tumaini","family":"Nagu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Muhimbili University of Health and Allied Sciences , Dar es Salaam ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Said","family":"Aboud","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences , Dar es Salaam ,","place":["Tanzania"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"2025060219523023600_dkaf125-B1","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/S0140-6736(13)61998-4","article-title":"Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?","volume":"382","author":"Cohen","year":"2013","journal-title":"Lancet"},{"key":"2025060219523023600_dkaf125-B2","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/j.jiph.2022.08.012","article-title":"Systematic review of interventions aimed at improving HIV adherence to care in low- and middle-income countries in sub-Saharan Africa","volume":"15","author":"Pugh","year":"2022","journal-title":"J Infect Public Health"},{"key":"2025060219523023600_dkaf125-B3","doi-asserted-by":"publisher","first-page":"e0272405","DOI":"10.1371\/journal.pone.0272405","article-title":"Achieving the 95 95 95 targets for all: a pathway to ending AIDS","volume":"17","author":"Frescura","year":"2022","journal-title":"PLoS One"},{"key":"2025060219523023600_dkaf125-B4","doi-asserted-by":"publisher","first-page":"e0284767","DOI":"10.1371\/journal.pone.0284767","article-title":"High acceptability and viral suppression rate for first-line patients on a dolutegravir-based regimen: an early adopter study in Nigeria","volume":"18","author":"Abudiore","year":"2023","journal-title":"PLoS One"},{"key":"2025060219523023600_dkaf125-B5","doi-asserted-by":"publisher","first-page":"e33737","DOI":"10.1097\/MD.0000000000033737","article-title":"Viral suppression in the era of transition to dolutegravir-based therapy in Cameroon: children at high risk of virological failure due to the lowly transition in pediatrics","volume":"102","author":"Fokam","year":"2023","journal-title":"Medicine (Baltimore)"},{"key":"2025060219523023600_dkaf125-B6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12981-021-00338-y","article-title":"Predictors of failure on second-line antiretroviral therapy with protease inhibitor mutations in Uganda","volume":"18","author":"Musana","year":"2021","journal-title":"AIDS Res Ther"},{"key":"2025060219523023600_dkaf125-B7","author":"Program NAC"},{"key":"2025060219523023600_dkaf125-B8","volume-title":"Paediatric DTG Implementation Considerations for National Programmes","author":"WHO","year":"2022"},{"key":"2025060219523023600_dkaf125-B9","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1186\/s12879-018-3372-6","article-title":"Virological failure among adolescents on ART, Harare City, 2017\u2014a case-control study","volume":"18","author":"Sithole","year":"2018","journal-title":"BMC Infect Dis"},{"key":"2025060219523023600_dkaf125-B10","doi-asserted-by":"publisher","first-page":"877","DOI":"10.2147\/HIV.S323445","article-title":"Rate of viral re-suppression and retention to care among PLHIV on second-line antiretroviral therapy at Dessie Comprehensive Specialized Hospital, Northeast Ethiopia: a retrospective cohort study","volume":"13","author":"Wedajo","year":"2021","journal-title":"HIV AIDS (Auckl)"},{"key":"2025060219523023600_dkaf125-B11","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1186\/s12879-024-09161-y","article-title":"HIV viral suppression and risk of viral rebound in patients on antiretroviral therapy: a two- year retrospective cohort study in Northern Tanzania","volume":"24","author":"Kahabuka","year":"2024","journal-title":"BMC Infect Dis"},{"key":"2025060219523023600_dkaf125-B12","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12981-021-00391-7","article-title":"Determinants of viral suppression among adolescents on antiretroviral treatment in Ehlanzeni district, South Africa: a cross-sectional analysis","volume":"18","author":"Okonji","year":"2021","journal-title":"AIDS Res Ther"},{"key":"2025060219523023600_dkaf125-B13","doi-asserted-by":"publisher","first-page":"1309740","DOI":"10.3389\/frph.2024.1309740","article-title":"Trend and factors associated with non-suppression of viral load among adolescents on ART in Tanzania: 2018\u20132021","volume":"6","author":"Quaker","year":"2024","journal-title":"Front Reprod Health"},{"key":"2025060219523023600_dkaf125-B14","doi-asserted-by":"publisher","first-page":"769627","DOI":"10.1155\/2011\/769627","article-title":"Protease inhibitor resistance is uncommon in HIV-1 subtype C infected patients on failing second-line lopinavir\/r-containing antiretroviral therapy in South Africa","volume":"2011","author":"Wallis","year":"2011","journal-title":"AIDS Res Treat"},{"key":"2025060219523023600_dkaf125-B15","doi-asserted-by":"publisher","first-page":"e32144","DOI":"10.1371\/journal.pone.0032144","article-title":"Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa","volume":"7","author":"Levison","year":"2012","journal-title":"PLoS One"},{"key":"2025060219523023600_dkaf125-B16","doi-asserted-by":"publisher","first-page":"38","DOI":"10.7448\/IAS.15.5.18438","article-title":"High levels of drug resistance after failure of first-line antiretroviral therapy in rural South Africa: impact on standardised second-line regimens","volume":"15","author":"Manasa","year":"2012","journal-title":"J Int AIDS Soc"},{"key":"2025060219523023600_dkaf125-B17","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1097\/QAI.0000000000001923","article-title":"A clinical prediction rule for protease inhibitor resistance in patients failing second-line antiretroviral therapy","volume":"80","author":"Cohen","year":"2019","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2025060219523023600_dkaf125-B18","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s12879-021-05905-2","article-title":"Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa","volume":"21","author":"Obasa","year":"2021","journal-title":"BMC Infect Dis"},{"key":"2025060219523023600_dkaf125-B19","doi-asserted-by":"publisher","first-page":"e0227600","DOI":"10.1371\/journal.pone.0227600","article-title":"High failure rates of protease inhibitor-based antiretroviral treatment in rural Tanzania\u2014a prospective cohort study","volume":"15","author":"Bircher","year":"2020","journal-title":"PLoS One"},{"key":"2025060219523023600_dkaf125-B20","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s12981-021-00393-5","article-title":"Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa","volume":"18","author":"Chimukangara","year":"2021","journal-title":"AIDS Res Ther"},{"key":"2025060219523023600_dkaf125-B21","doi-asserted-by":"publisher","first-page":"e0228601","DOI":"10.1371\/journal.pone.0228601","article-title":"Zimbabwe's national third-line antiretroviral therapy program: cohort description and treatment outcomes","volume":"15","author":"Chimbetete","year":"2020","journal-title":"PLoS One"},{"key":"2025060219523023600_dkaf125-B22","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1093\/infdis\/jiw219","article-title":"Protease inhibitor resistance in the first 3 years of second-line antiretroviral therapy for HIV-1 in Sub-Saharan Africa","volume":"214","author":"Boender","year":"2016","journal-title":"J Infect Dis"},{"key":"2025060219523023600_dkaf125-B23","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1093\/cid\/cix1108","article-title":"Effectiveness of protease inhibitor\/nucleos(t)ide reverse transcriptase inhibitor-based second-line antiretroviral therapy for the treatment of human immunodeficiency virus type 1 infection in Sub-Saharan Africa: a systematic review and meta-analysis","volume":"66","author":"Stockdale","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2025060219523023600_dkaf125-B24","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.bjid.2017.02.001","article-title":"Virological suppression in children and adolescents is not influenced by genotyping, but depends on optimal adherence to antiretroviral therapy","volume":"21","author":"Abreu","year":"2017","journal-title":"Braz J Infect Dis"},{"key":"2025060219523023600_dkaf125-B25","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.4102\/sajhivmed.v20i1.1002","article-title":"Challenges to HIV treatment adherence amongst adolescents in a low socio-economic setting in Cape Town","volume":"20","author":"van Wyk","year":"2019","journal-title":"South Afr J HIV Med"},{"key":"2025060219523023600_dkaf125-B26","doi-asserted-by":"publisher","first-page":"23259582211062754","DOI":"10.1177\/23259582211062754","article-title":"Adolescents and young adults knowledge, adherence and experiences while on antiretroviral therapy in a tertiary hospital in Lagos, Nigeria: a mixed-method study","volume":"20","author":"Aderemi-Williams","year":"2021","journal-title":"J Int Assoc Provid AIDS Care"},{"key":"2025060219523023600_dkaf125-B27","doi-asserted-by":"publisher","first-page":"594","DOI":"10.3390\/v13040594","article-title":"HIV-1 subtype C drug resistance mutations in heavily treated patients failing integrase strand transfer inhibitor-based regimens in Botswana","volume":"13","author":"Seatla","year":"2021","journal-title":"Viruses"},{"key":"2025060219523023600_dkaf125-B28","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1007\/s13337-021-00725-z","article-title":"Drug resistance mutations in protease gene of HIV-1 subtype C infected patient population","volume":"32","author":"Misbah","year":"2021","journal-title":"Virusdisease"},{"key":"2025060219523023600_dkaf125-B29","doi-asserted-by":"publisher","first-page":"e10562","DOI":"10.1097\/MD.0000000000010562","article-title":"Viral suppression and viral rebound among young adults living with HIV in Canada","volume":"97","author":"Palmer","year":"2018","journal-title":"Medicine (Baltimore)"},{"key":"2025060219523023600_dkaf125-B30","doi-asserted-by":"publisher","first-page":"2049936120920177","DOI":"10.1177\/2049936120920177","article-title":"Antiretroviral adherence for adolescents growing up with HIV: understanding real life, drug delivery and forgiveness","volume":"7","author":"Foster","year":"2020","journal-title":"Ther Adv Infect Dis"},{"key":"2025060219523023600_dkaf125-B31","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1093\/infdis\/jit411","article-title":"Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch","volume":"209","author":"Johnston","year":"2014","journal-title":"J Infect Dis"},{"key":"2025060219523023600_dkaf125-B32","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1111\/hiv.13006","article-title":"Virological failure and HIV drug resistance among adults living with HIV on second-line antiretroviral therapy in the Asia-Pacific","volume":"22","author":"Ross","year":"2021","journal-title":"HIV Med"},{"issue":"Suppl 2","key":"2025060219523023600_dkaf125-B33","doi-asserted-by":"publisher","first-page":"S49","DOI":"10.1093\/infdis\/jit107","article-title":"Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings","volume":"207","author":"Hosseinipour","year":"2013","journal-title":"J Infect Dis"},{"key":"2025060219523023600_dkaf125-B34","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1186\/s12879-024-09156-9","article-title":"HIV protease resistance mutations in patients receiving second-line antiretroviral therapy in Libreville, Gabon","volume":"24","author":"Nzengui-Nzengui","year":"2024","journal-title":"BMC Infect Dis"},{"key":"2025060219523023600_dkaf125-B35","doi-asserted-by":"publisher","first-page":"e0223210","DOI":"10.1371\/journal.pone.0223210","article-title":"Major drug resistance mutations to HIV-1 protease inhibitors (PI) among patients exposed to PI class failing antiretroviral therapy in S\u00e3o Paulo state, Brazil","volume":"14","author":"Soldi","year":"2019","journal-title":"PLoS One"},{"key":"2025060219523023600_dkaf125-B36","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.eclinm.2019.03.006","article-title":"Trends in pretreatment HIV-1 drug resistance in antiretroviral therapy-naive adults in South Africa, 2000\u20132016: a pooled sequence analysis","volume":"9","author":"Chimukangara","year":"2019","journal-title":"EClinicalMedicine"},{"key":"2025060219523023600_dkaf125-B37","doi-asserted-by":"publisher","first-page":"136","DOI":"10.24875\/AIDSRev.23000002","article-title":"The impact of the M184V resistance mutation on treatment outcomes in patients with HIV infection: a systematic review and meta-analysis","volume":"26","author":"Kandeel","year":"2023","journal-title":"AIDS Rev"},{"key":"2025060219523023600_dkaf125-B38","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1093\/jac\/dkw039","article-title":"Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk","volume":"71","author":"Inzaule","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2025060219523023600_dkaf125-B39","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1086\/505711","article-title":"Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level","volume":"194","author":"Parikh","year":"2006","journal-title":"J Infect Dis"},{"key":"2025060219523023600_dkaf125-B40","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1186\/s12879-017-2709-x","article-title":"Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: implications for the activity of next-line regimens from a longitudinal study in Mozambique","volume":"17","author":"De Luca","year":"2017","journal-title":"BMC Infect Dis"},{"key":"2025060219523023600_dkaf125-B41","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1111\/hiv.12400","article-title":"HIV drug resistance levels in adults failing first-line antiretroviral therapy in an urban and a rural setting in South Africa","volume":"18","author":"Rossouw","year":"2017","journal-title":"HIV Med"},{"key":"2025060219523023600_dkaf125-B42","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12981-018-0206-y","article-title":"Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay","volume":"15","author":"Silver","year":"2018","journal-title":"AIDS Res Ther"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/6\/1694\/63042469\/dkaf125.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/6\/1694\/63042469\/dkaf125.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T23:52:37Z","timestamp":1748908357000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/80\/6\/1694\/8123790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,2]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,5,2]]},"published-print":{"date-parts":[[2025,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkaf125","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,5,2]]}}}