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Adolescent girls and young women (AGYW) have been prioritised for PrEP delivery in South Africa. A combination HIV prevention intervention providing integrated biomedical, behavioural and structural interventions for AGYW aged 15\u201324 in twelve districts in South Africa characterised by high HIV prevalence, was implemented 2019\u20132022. We conducted qualitative interviews to explore PrEP implementation experiences with 38 individuals involved in the implementation of the combination HIV prevention programme, including programme managers and project coordinators, health care providers \/ nurses, social workers, counsellors, peer group trainers and outreach workers. Narratives included various challenges associated with PrEP uptake, adherence and acceptability experienced by implementers. Barriers to PrEP acceptability included AGYW fears of side effects and preference for injectable versus daily oral PrEP; resistance towards PrEP from AGYW, communities and parents due to a lack of accurate information; PrEP stigma linked to associations with antiretrovirals and assumptions of promiscuity; and issues pertaining to parental consent. Additionally, implementers faced logistical challenges related to procurement, stockouts, and supply of PrEP. Findings highlighted the critical role of parental and community acceptability of PrEP for successful implementation. Overall, PrEP was perceived by implementers as a valuable HIV prevention tool. In order to ensure the accessibility of PrEP for AGYW in South Africa, efforts to reduce stigma and foster social support for PrEP use, campaigns to raise awareness, ensure positive framing of PrEP, and build community acceptability of PrEP, are needed.<\/jats:p>","DOI":"10.1007\/s10461-022-03750-1","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T11:03:42Z","timestamp":1657105422000},"page":"134-149","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["\u201cThese Girls Have a Chance to be the Future Generation of HIV Negative\u201d: Experiences of Implementing a PrEP Programme for Adolescent Girls and Young Women in South Africa"],"prefix":"10.1007","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7615-8152","authenticated-orcid":false,"given":"Zoe","family":"Duby","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Bunce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Jonas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Bergh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshini","family":"Govindasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Mathews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"issue":"10","key":"3750_CR1","doi-asserted-by":"publisher","first-page":"e25626","DOI":"10.1002\/jia2.25626","volume":"23","author":"K Gill","year":"2020","unstructured":"Gill K, Happel A-U, Pidwell T, Mendelsohn A, Duyver M, Johnson L, Meyer L, Slack C, Strode A, Mendel E, Fynn L, Wallace M, Spiegel H, Jaspan H, Passmore J-A, Hosek S, Smit D, Rinehart A, Bekker LG. 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