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Treatment with long-acting (LA), injection-based ART administered by healthcare professionals (directly observed therapy (DOT)) eliminates the need for adherence to daily dosing and may improve clinical outcomes. This study reports the cost-effectiveness of the cabotegravir plus rilpivirine LA regimen (CAB+RPV LA) and models the potential impact of LA DOT therapies.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>Parameterisation was performed using pooled data from recent CAB+RPV LA Phase III trials. The analysis was conducted using a cohort-level hybrid decision-tree and state-transition model, with states defined by viral load and CD4 cell count. The efficacy of oral cART was adjusted to reflect adherence to daily regimens from published data. A Canadian health service perspective was adopted.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>CAB+RPV LA is predicted to be the dominant intervention when compared to oral cART, generating, per 1,000 patients treated, lifetime cost-savings of $1.5 million, QALY and life-year gains of 107 and 138 respectively with three new HIV cases averted.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>Economic evaluations of LA DOTs need to account for the impact of adherence and HIV transmission. This study adds to the existing literature by incorporating transmission and using clinical data from the first LA DOT regimen. Providing PLWH and healthcare providers with novel modes of ART administration, enhancing individualisation of treatment, may facilitate the achievement of UNAIDS 95-95-95 objectives.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0245955","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T19:07:26Z","timestamp":1612292846000},"page":"e0245955","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":29,"title":["Cost-effectiveness of the long-acting regimen cabotegravir plus rilpivirine for the treatment of HIV-1 and its potential impact on adherence and viral transmission: A modelling study"],"prefix":"10.1371","volume":"16","author":[{"given":"Ben","family":"Parker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9944-5450","authenticated-orcid":true,"given":"Olivia","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Arthurs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah-Jane","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Chounta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Van de Velde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"issue":"13","key":"pone.0245955.ref001","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1097\/QAD.0b013e328362ba67","article-title":"The burden of HIV: insights from the Global Burden of Disease Study 2010","volume":"27","author":"KF Ortblad","year":"2013","journal-title":"AIDS (London, England)"},{"key":"pone.0245955.ref002","unstructured":"UNAIDS. 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