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Despite widespread calls to combine structural, behavioural and biomedical HIV prevention interventions, this has not been delivered at scale. In this commentary, we reflect on the two\u2010year rollout of DREAMS in a high HIV incidence, rural and poor community in northern KwaZulu\u2010Natal, South Africa to critically appraise the capacity for a centrally co\u2010ordinated and AGYW\u2010focused approach to combination HIV prevention to support sustainable development for adolescents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>DREAMS employed a directed target\u2010focused approach in which local implementing partners were resourced to deliver defined packages to AGYW in selected geographical areas over two years. We argue that this approach, with high\u2010level oversight by government and funders, enabled the rapid roll\u2010out of ambitious multi\u2010sectoral HIV prevention for AGYW. It was most successful at delivering multiple interventions for AGYW when it built on existing infrastructure and competencies, and\/or allocated resources to address existing youth development concerns of the community. The approach would have been strengthened if it had included a mechanism to solicit and then respond to the concerns of young women, for example gender\u2010related norms and how young women experience their sexuality, and if this listening was supported by versatility to adapt to the social context. In a context of high HIV vulnerability across all adolescents and youth, an over\u2010emphasis on targeting specific groups, whether geographically or by risk profile, may have hampered acceptability and reach of the intervention. Absence of meaningful engagement of AGYW in the development, delivery and leadership of the intervention was a lost opportunity to achieve sustainable development goals among young people and shift gender\u2010norms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Centrally directed and target\u2010focused scale\u2010up of defined packages of HIV prevention across sectors was largely successful in reaching AGYW in this rural South African setting rapidly. However, to achieve sustainable and successful long\u2010term youth development and transformation of gender\u2010norms there is a need for greater adaptability, economic empowerment and meaningful engagement of AGYW in the development and delivery of interventions. Achieving this will require sustained commitment from government and funders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25575","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T06:16:31Z","timestamp":1598940991000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Directed and target focused multi\u2010sectoral adolescent HIV prevention: Insights from implementation of the \u2018DREAMS Partnership\u2019 in rural South Africa"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3125-978X","authenticated-orcid":false,"given":"Natsayi","family":"Chimbindi","sequence":"first","affiliation":[{"name":"Africa Health Research Institute Mtubatuba South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5742-6588","authenticated-orcid":false,"given":"Isolde","family":"Birdthistle","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Floyd","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6604-491X","authenticated-orcid":false,"given":"Guy","family":"Harling","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute Mtubatuba South Africa"},{"name":"Institute for Global Health University College London London United Kingdom"},{"name":"Harvard University Boston MA USA"},{"name":"University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nondumiso","family":"Mthiyane","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute Mtubatuba South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thembelihle","family":"Zuma","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute Mtubatuba South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3509-3572","authenticated-orcid":false,"given":"James R","family":"Hargreaves","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-5272","authenticated-orcid":false,"given":"Janet","family":"Seeley","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute Mtubatuba South Africa"},{"name":"London School of Hygiene and Tropical Medicine London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7129-8535","authenticated-orcid":false,"given":"Maryam","family":"Shahmanesh","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute Mtubatuba South Africa"},{"name":"Institute for Global Health University College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"UNAIDS.HIV prevention among adolescent girls and young women: Putting HIV prevention among adolescent girls and young women on the Fast\u2010Track and engaging men and boys UNAIDS.2016."},{"key":"e_1_2_7_3_1","unstructured":"Human Sciences Research Council (HSRC).The Fifth South African National HIV Prevalence Incidence Behaviour and Communication Survey 2017: HIV Impact Assessment Summary Report. 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