{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T08:17:01Z","timestamp":1762157821147,"version":"3.41.2"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,3,27]],"date-time":"2020-03-27T00:00:00Z","timestamp":1585267200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["101113\/Z\/13\/Z","203077\/Z\/16\/Z"],"award-info":[{"award-number":["101113\/Z\/13\/Z","203077\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern AIDS Soc"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Many HIV\u2010positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced\u2010prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 &lt;100\u00a0cells\/mm<jats:sup>3<\/jats:sup>. We investigated the cost\u2010effectiveness of this enhanced\u2010prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 &lt;200\u00a0cells\/mm<jats:sup>3<\/jats:sup>or &lt;100\u00a0cells\/mm<jats:sup>3<\/jats:sup>at ART initiation and all individuals regardless of CD4 count.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The REALITY trial enrolled from June 2013 to April 2015. A decision\u2010analytic model was developed to estimate the cost\u2010effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard\u2010prophylaxis, enhanced\u2010prophylaxis, standard\u2010prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced\u2010prophylaxis (CrAg\u2010positive) or standard\u2010prophylaxis (CrAg\u2010negative), the second to enhanced\u2010prophylaxis (CrAg\u2010positive) or enhanced\u2010prophylaxis without fluconazole (CrAg\u2010negative) and the third to standard\u2010prophylaxis with fluconazole (CrAg\u2010positive) or without fluconazole (CrAg\u2010negative). The model estimated costs, life\u2010years and quality\u2010adjusted life\u2010years (QALY) over 48\u00a0weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Enhanced\u2010prophylaxis was cost\u2010effective at cost\u2010effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost\u2010effectiveness ratio (ICER) of US$157 per QALY in the CD4 &lt;200\u00a0cells\/mm<jats:sup>3<\/jats:sup>population providing enhanced\u2010prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 &lt;100\u00a0cells\/mm<jats:sup>3<\/jats:sup>population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced\u2010prophylaxis components. Enhanced\u2010prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced\u2010prophylaxis still conveyed health gains in CrAg\u2010negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost\u2010effective unless the price of CrAg testing fell below US$2.30.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The REALITY enhanced\u2010prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost\u2010effective. Efforts should continue to ensure that components are accessed at lowest available prices.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25469","type":"journal-article","created":{"date-parts":[[2020,3,27]],"date-time":"2020-03-27T08:04:49Z","timestamp":1585296289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The cost\u2010effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-3691","authenticated-orcid":false,"given":"Simon M","family":"Walker","sequence":"first","affiliation":[{"name":"Centre for Health Economics University of York York UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Cox","sequence":"additional","affiliation":[{"name":"Centre for Health Economics University of York York UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Revill","sequence":"additional","affiliation":[{"name":"Centre for Health Economics University of York York UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Musiime","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre Kampala Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutsa","family":"Bwakura\u2010Dangarembizi","sequence":"additional","affiliation":[{"name":"University of Zimbabwe Clinical Research Centre Harare Zimbabwe"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Mallewa","sequence":"additional","affiliation":[{"name":"College of Medicine University of Malawi and Malawi\u2010Liverpool\u2010Wellcome Trust Clinical Research Programme Blantyre Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscilla","family":"Cheruiyot","sequence":"additional","affiliation":[{"name":"Moi University School of Medicine Eldoret Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Maitland","sequence":"additional","affiliation":[{"name":"KEMRI Wellcome Trust Research Programme Kilifi Kenya"},{"name":"Department of Infectious Diseases Imperial College London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1482-3967","authenticated-orcid":false,"given":"Nathan","family":"Ford","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Department and Global Hepatitis Programme World Health Organization Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana M","family":"Gibb","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit UCL London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Sarah","family":"Walker","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit UCL London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Soares","sequence":"additional","affiliation":[{"name":"Centre for Health Economics University of York York UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the REALITY trial team","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy045"},{"issue":"1","key":"e_1_2_9_3_1","first-page":"1","article-title":"Immunodeficiency at the start of combination antiretroviral therapy in low\u2010, middle\u2010 and high\u2010income countries","volume":"65","author":"Egger M","year":"2013","journal-title":"JAIDS J Acquir Immune Defic Syndr"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix915"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(15)00137-X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028691"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.7448\/IAS.19.1.20714"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000802"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-10-67"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615822"},{"key":"e_1_2_9_12_1","unstructured":"WHO.Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy.WHO[Internet].2017[cited 2017 Sep 27]. 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