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This analysis projects the impact of expanding PrEP coverage with CAB\u2010LA in South Africa between 2022 and 2042.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three independently calibrated models of HIV transmission in South Africa (Synthesis, EMOD\u2010HIV, Thembisa) projected HIV acquisitions and effective coverage (average PrEP coverage across exposure groups, weighted by HIV incidence in the absence of PrEP in each group) over 20 years under multiple scenarios of PrEP expansion compared to no PrEP expansion. PrEP expansion scenarios differed in targeted overall coverage, speed of expansion, coverage of high\u2010exposure groups, and relative coverage of women and men.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Achieving 5% PrEP coverage with CAB\u2010LA by 2032 prioritizing high\u2010exposure groups resulted in 49% (Synthesis), 18% (EMOD\u2010HIV), and 8% (Thembisa) effective coverage and averted a median of 43%, 29% and 10% of new HIV acquisitions, respectively. Similar expansion with TDF\/FTC resulted in lower impact by 19 percentage points (pp), 18pp and 3pp, respectively. Increasing CAB\u2010LA coverage to 15% led to an additional 7pp, 12pp and 16pp, respectively, of HIV acquisitions averted. Achieving 5% CAB\u2010LA coverage expanding to women only resulted in a lower impact by 16pp (Synthesis) and 13pp (EMOD\u2010HIV), and a higher impact by 2pp (Thembisa). Scenarios with similar effective coverage resulted in comparable impact estimates across models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Offering CAB\u2010LA in South Africa may substantially impact the HIV epidemic based on these projections. Effective coverage proved to be a good predictor of intervention effectiveness.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.26453","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:30:03Z","timestamp":1751441403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Estimated impact of long\u2010acting injectable PrEP in South Africa: a model comparison analysis"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3251-8501","authenticated-orcid":false,"given":"Sarah E.","family":"Stansfield","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5055-7075","authenticated-orcid":false,"given":"Mia","family":"Moore","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center  Seattle Washington 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