{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:21:14Z","timestamp":1790968874311,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"national institute of mental health","doi-asserted-by":"publisher","award":["P30-MH43520"],"award-info":[{"award-number":["P30-MH43520"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"eunice kennedy shriver national institute of child health and human development","doi-asserted-by":"publisher","award":["4UH3HD096926"],"award-info":[{"award-number":["4UH3HD096926"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Adolescents and youth living with HIV (AYAHIV) have worse HIV outcomes than other age groups, particularly in sub-Saharan Africa (SSA). AYAHIV in SSA face formidable health system, interpersonal- and individual-level barriers to retention in HIV care, uptake of ART, and achievement of viral suppression (VS), underscoring an urgent need for multi-component interventions to address these challenges. This cluster-randomized control trial (cRCT) aims to evaluate the effectiveness and monitor implementation of a community-informed multi-component intervention (\u201cCombinADO strategy\u201d) addressing individual-, facility-, and community-level factors to improve health outcomes for AYAHIV.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This trial will be conducted in 12 clinics in Nampula Province, Northern Mozambique. All clinics will implement an optimized standard of care (control) including (1) billboards\/posters and radio shows, (2) healthcare worker (HCW) training, (3) one-stop adolescent and youth-friendly services, (4) information\/motivation walls, (5) pill containers, and (6) tools to be used by HCW during clinical visits. The CombinADO strategy (intervention) will be superadded to control conditions at 6 randomly selected clinics. It will include five additional components: (1) peer support, (2) informational\/motivational video, (3) support groups for AYAHIV caregivers, (4) AYAHIV support groups, and (5) mental health screening and linkage to adolescent-focused mental health support. The study conditions will be in place for 12\u2009months; all AYAHIV (ages 10\u201324\u2009years, on ART) seeking care in the participating sites will be exposed to either the control or intervention condition based on the clinic they attend. The primary outcome is VS (viral load &lt;\u200950 copies\/mL) at 12\u2009months among AYAHIV attending participating clinics. Secondary outcomes include ART adherence (self-reported and TDF levels) and retention in care (engagement in the preceding 90\u2009days). Uptake, feasibility, acceptability, and fidelity of the CombinADO strategy during implementation will be measured. Trial outcomes will be assessed in AYAHIV, caregivers, healthcare workers, and key informants. Statistical analyses will be conducted and reported in line with CONSORT guidelines for cRCTs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>The CombinADO study will provide evidence on effectiveness and inform implementation of a novel community-informed multi-component intervention to improve retention, adherence, and VS among AYAHIV. If found effective, results will strengthen the rationale for scale up in SSA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04930367\">ClinicalTrials.gov NCT04930367<\/jats:ext-link>. Registered on 18 June 2021<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-021-05943-w","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T11:05:55Z","timestamp":1640603155000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The CombinADO study to assess the impact of a combination intervention strategy on viral suppression, antiretroviral therapy adherence, and retention in HIV care among adolescents and young people living with HIV: protocol for a cluster-randomized controlled trial"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0721-5576","authenticated-orcid":false,"given":"Phepo","family":"Mogoba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maia","family":"Lesosky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Zerbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Falcao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude Ann","family":"Mellins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Desmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Arnaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill","family":"Kapogiannis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Landon","family":"Myer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine J.","family":"Abrams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"key":"5943_CR1","unstructured":"UNICEF. Children & AIDS: ALL IN to #EndAdolescentAIDS. Available from: https:\/\/childrenandaids.org\/all-in-to-end-adolescent-AIDS. Accessed 20 June 2020."},{"key":"5943_CR2","unstructured":"UNAIDS. UNAIDS data 2019. 2019. Available from: https:\/\/www.unaids.org\/en\/resources\/documents\/2019\/2019-UNAIDS-data."},{"key":"5943_CR3","unstructured":"Avert. Young people, HIV and AIDS. Available from: https:\/\/www.avert.org\/professionals\/hiv-social-issues\/key-affected-populations\/young-people. Accessed 15 Aug 2020."},{"key":"5943_CR4","unstructured":"ICAP at Columbia University. PHIA Project. Available from: http:\/\/phia.icap.columbia.edu."},{"issue":"1","key":"5943_CR5","doi-asserted-by":"publisher","first-page":"21437","DOI":"10.7448\/IAS.20.1.21437","volume":"20","author":"MH Kim","year":"2017","unstructured":"Kim MH, Mazenga AC, Yu X, Ahmed S, Paul ME, Kazembe PN, et al. High self-reported non-adherence to antiretroviral therapy amongst adolescents living with HIV in Malawi: barriers and associated factors. J Int AIDS Soc. 2017;20(1):21437.","journal-title":"J Int AIDS Soc"},{"issue":"7","key":"5943_CR6","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1080\/09540121.2011.644234","volume":"24","author":"J Kamau","year":"2012","unstructured":"Kamau J, Kuria W, Mathai M, Atwoli L, Kangethe R. Psychiatric morbidity among HIV-infected children and adolescents in a resource-poor Kenyan urban community. AIDS Care. 2012;24(7):836\u201342. https:\/\/doi.org\/10.1080\/09540121.2011.644234.","journal-title":"AIDS Care."},{"key":"5943_CR7","unstructured":"Dow MD D, Shayo A, Sullivan K, Cunningham C, McKellar Dr. M, O\u2019Donnell K. Establishing mental health needs among HIV-positive children in Tanzania. Paper presented at: 20th International AIDS Conference; 2014 July 20-25; Melbourne, Australia."},{"key":"5943_CR8","unstructured":"Statistics of South Africa. Millennium Development Goals, Country Report 2013. Country Report Statistics South Africa. Pretoria: Statistics South Africa; 2013. Available from: https:\/\/www.gov.za\/documents\/millennium-development-goals-country-report-2013. Accessed 11 Sept 2020."},{"issue":"2","key":"5943_CR9","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1080\/09540121.2017.1344349","volume":"30","author":"CD Fair","year":"2018","unstructured":"Fair CD, Berk M. Provider perceptions of stigma and discrimination experienced by adolescents and young adults with pHiV while accessing sexual and reproductive health care. AIDS Care. 2018;30(2):178\u201381. https:\/\/doi.org\/10.1080\/09540121.2017.1344349.","journal-title":"AIDS Care."},{"issue":"6","key":"5943_CR10","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1080\/09540121.2017.1391986","volume":"30","author":"MW Gichane","year":"2018","unstructured":"Gichane MW, Sullivan KA, Shayo AM, Mmbaga BT, O\u2019Donnell K, Cunningham CK, et al. Caregiver role in HIV medication adherence among HIV-infected orphans in Tanzania. AIDS Care. 2018;30(6):701\u20135. https:\/\/doi.org\/10.1080\/09540121.2017.1391986.","journal-title":"AIDS Care."},{"issue":"1","key":"5943_CR11","doi-asserted-by":"publisher","first-page":"18839","DOI":"10.7448\/IAS.17.1.18839","volume":"17","author":"J Busza","year":"2014","unstructured":"Busza J, Dauya E, Bandason T, Mujuru H, Ferrand RA. \u201cI don\u2019t want financial support but verbal support.\u201d How do caregivers manage children\u2019s access to and retention in HIV care in urban Zimbabwe? J Int AIDS Soc. 2014;17(1):18839.","journal-title":"J Int AIDS Soc"},{"issue":"4","key":"5943_CR12","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1371\/journal.pone.0250218","volume":"16","author":"CA Teasdale","year":"2021","unstructured":"Teasdale CA, Brittain K, Zerbe A, Mellins CA, Falcao J, Couto A, et al. Characteristics of adolescents aged 15-19 years living with vertically and horizontally acquired HIV in Nampula. Mozambique. PLoS One. 2021;16(4):16\u20139. https:\/\/doi.org\/10.1371\/journal.pone.0250218.","journal-title":"Mozambique. PLoS One."},{"key":"5943_CR13","first-page":"73","volume":"8","author":"J Falcao","year":"2020","unstructured":"Falcao J, Zerbe A, Kapogiannis B, Simione B, Pimentel De Gusmao E, Brittain K, et al. The secret life of young adolescents living with HIV in northern Mozambique-a mixed method study. Rev Antivir Ther Infect Dis. 2020;8:73.","journal-title":"Rev Antivir Ther Infect Dis"},{"key":"5943_CR14","unstructured":"Carey S, Kolada B, Olmedo B, Shadwick C, Singhal H, Falcao J, et al. Designing for hope: addressing adherence by looking beyond the pill. A co-creation approach to addressing multidimensional factors that impact ART adherence and retention among adolescents living with HIV in Mozambique. Paper presented at: 23rd International AIDS Conference; 2020 July 6-10; San Francisco, CA, US."},{"issue":"3","key":"5943_CR15","doi-asserted-by":"publisher","first-page":"e25028","DOI":"10.1002\/jia2.25028","volume":"20","author":"RK MacKenzie","year":"2017","unstructured":"MacKenzie RK, van Lettow M, Gondwe C, Nyirongo J, Singano V, Banda V, et al. Greater retention in care among adolescents on antiretroviral treatment accessing \u201cTeen Club\u201d an adolescent-centred differentiated care model compared with standard of care: a nested case-control study at a tertiary referral hospital in Malawi. J Int AIDS Soc. 2017;20(3):e25028. https:\/\/doi.org\/10.1002\/jia2.25028.","journal-title":"J Int AIDS Soc."},{"issue":"2","key":"5943_CR16","doi-asserted-by":"publisher","first-page":"e264","DOI":"10.1016\/S2214-109X(19)30526-1","volume":"8","author":"W Mavhu","year":"2020","unstructured":"Mavhu W, Willis N, Mufuka J, Bernays S, Tshuma M, Mangenah C, et al. Effect of a differentiated service delivery model on virological failure in adolescents with HIV in Zimbabwe (Zvandiri): a cluster-randomised controlled trial. Lancet Glob Heal. 2020;8(2):e264\u201375. https:\/\/doi.org\/10.1016\/S2214-109X(19)30526-1.","journal-title":"Lancet Glob Heal."},{"issue":"8","key":"5943_CR17","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1111\/tmi.12517","volume":"20","author":"P MacPherson","year":"2015","unstructured":"MacPherson P, Munthali C, Ferguson J, Armstrong A, Kranzer K, Ferrand RA, et al. Service delivery interventions to improve adolescents\u2019 linkage, retention and adherence to antiretroviral therapy and HIV care. Trop Med Int Heal. 2015;20(8):1015\u201332. https:\/\/doi.org\/10.1111\/tmi.12517.","journal-title":"Trop Med Int Heal."},{"key":"5943_CR18","unstructured":"UNAIDS. UNAIDS Data 2017. Geneva: UNAIDS Joint United National Programme on HIV\/AIDS. 2017. Available from: https:\/\/www.unaids.org\/en\/resources\/documents\/2017\/2017_data_book."},{"key":"5943_CR19","unstructured":"National Institute of Statistics. Mozambique National Institute of Statistics, 2017.. 2017. Available from: http:\/\/ghdx.healthdata.org\/organizations\/national-institute-statistics-ine-mozambique."},{"key":"5943_CR20","unstructured":"MISAU. Relat\u00f3rio Semestral 2020. In: Relat\u00f3rio Semestral das Actividades Relacionadas ao HIV\/SIDA . MISAU program data; 2020 June."},{"key":"5943_CR21","unstructured":"UNAIDS. Country factsheets. Available from: https:\/\/www.unaids.org\/en\/regionscountries\/countries\/mozambique . Accessed 29 July 2020."},{"key":"5943_CR22","unstructured":"PEPFAR Mozambique. Mozambique Quarter I POART COP20\/FY21 Presentation. Slides presented: 2021 March18; 21 slides."},{"key":"5943_CR23","unstructured":"MISAU. Relat\u00f3rio Nonestral das actividades realizadas pelo Programa de Saude Escolar do Adolescente e Jovem, de Janeiro a Setembro (9 meses); 2021. 19 p. Report: Outubro de 2021."},{"key":"5943_CR24","unstructured":"CIPHER. Global research agendas for paediatric and adolescent HIV. Available from: https:\/\/www.iasociety.org\/HIV-Programmes\/Programmes\/Paediatrics-CIPHER\/Setting-global-research-priorities-for-children-and-adolescents-living-with-HIV. Accessed 30 Oct 2020."},{"key":"5943_CR25","unstructured":"PATCH3H. Available from: https:\/\/www.patc3h.org\/SitePages\/Home.aspx. Accessed 18 February 2021."},{"issue":"11","key":"5943_CR26","doi-asserted-by":"publisher","first-page":"2700","DOI":"10.1007\/s10461-016-1406-x","volume":"20","author":"IB Wilson","year":"2016","unstructured":"Wilson IB, Lee Y, Michaud J, Fowler FJ, Rogers WH. Validation of a new three-item self-report measure for medication adherence. AIDS and behavior. 2016;20(11):2700\u20138. https:\/\/doi.org\/10.1007\/s10461-016-1406-x.","journal-title":"AIDS and behavior."},{"issue":"12","key":"5943_CR27","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1007\/s10461-013-0610-1","volume":"18","author":"IB Wilson","year":"2014","unstructured":"Wilson IB, Fowler FJ, Cosenza CA, Michaud J, Bentkover J, Rana A, et al. Cognitive and field testing of a new set of medication adherence self-report items for HIV care. AIDS and behavior. 2014;18(12):2349\u201358. https:\/\/doi.org\/10.1007\/s10461-013-0610-1.","journal-title":"AIDS and behavior."}],"updated-by":[{"DOI":"10.1186\/s13063-022-06008-2","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000}}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-021-05943-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-021-05943-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-021-05943-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T11:06:22Z","timestamp":1642417582000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-021-05943-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["5943"],"URL":"https:\/\/doi.org\/10.1186\/s13063-021-05943-w","relation":{"correction":[{"id-type":"doi","id":"10.1186\/s13063-022-06008-2","asserted-by":"object"}]},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"8 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2022","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s13063-022-06008-2","URL":"https:\/\/doi.org\/10.1186\/s13063-022-06008-2","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Columbia University Irving Medical Center Institutional Review Board (CU-IRB) and the Comite Naticional De Bioetica Para A Saude (CNBS). All participants in this study will undergo written informed consenting procedures.","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 that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"956"}}