{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:28:25Z","timestamp":1786609705631,"version":"build-2736575974"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203905\/Z\/16\/Z"],"award-info":[{"award-number":["203905\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Trust Fellowship","award":["300088\/Z\/23\/Z"],"award-info":[{"award-number":["300088\/Z\/23\/Z"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K24AI184270"],"award-info":[{"award-number":["K24AI184270"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute for Health and Care Research (NIHR) through 2 Global Health Research Professorships","award":["RP-2017\u201308-ST2-012"],"award-info":[{"award-number":["RP-2017\u201308-ST2-012"]}]},{"name":"National Institute for Health and Care Research (NIHR) through 2 Global Health Research Professorships","award":["NIHR304266"],"award-info":[{"award-number":["NIHR304266"]}]},{"name":"UK government to support global health research"},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["D43TW009771"],"award-info":[{"award-number":["D43TW009771"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HIV and co-infections in Uganda","award":["D43TW012266"],"award-info":[{"award-number":["D43TW012266"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>One month of daily isoniazid and rifapentine (1HP) is an efficacious, well-tolerated, and safe tuberculosis-preventive therapy regimen. Its implementation has been slow due to concern about drug-drug interactions with rifapentine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-arm pharmacokinetic study included 15 adults with advanced human immunodeficiency virus (HIV) disease receiving once-daily 50-mg dolutegravir-based antiretroviral therapy during 1HP therapy, alongside once-daily 800-mg fluconazole for treatment of cryptococcal meningitis. Participants underwent intensive pharmacokinetic sampling on days 1, 5, and 14 of 1HP therapy; sampling was conducted before and 2, 4, 8, and 24 hours after dosing. Dolutegravir, rifapentine, and fluconazole plasma concentrations were measured by means of high-performance liquid chromatography mass spectrometry, and bioequivalence was assessed with standard 90% confidence intervals (CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifteen participants were enrolled, of whom 9 (60%) were female. The median age (interquartile range) was 37 (27\u201341) years, and the median CD4 cell count was 11\/\u03bcL (10\u201325\/\u03bcL). Overall, 14 of 15 participants completed sampling on days 5 and 14. The day 14 geometric mean (GM) dolutegravir trough concentration (95% CI) was 0.61 (.32\u20131.16) mg\/L, while the median (interquartile range) was 0.63 (0.34\u20130.87) mg\/L, with 100% of samples above the dolutegravir protein\u2013adjusted 90% inhibitory concentration of 0.064\u2005mg\/L, with a GM ratio of 0.76 (90% CI, .4\u20131.46) compared with day 1. The day 14 maximum plasma concentration and area under the concentration-time curve from 0 to 24\u2005hours for fluconazole were reduced compared with day 1, with GM ratios of 0.73 (90% CI, .57\u2013.94) and 0.77 (.64\u2013.93), respectively. Of 14 participants alive at 12 weeks after 1HP initiation, 11 (78%) had an HIV viral load (VL) &amp;lt;200 copies\/mL. No cases of cryptococcal meningitis relapse occurred during the 18-week follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Standard once-daily 50-mg dolutegravir and 800-mg fluconazole dosing may be a safe and effective option for patients receiving 1HP tuberculosis-preventive therapy. These findings support further evaluation in larger studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofag415","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:41:24Z","timestamp":1783424484000},"source":"Crossref","is-referenced-by-count":0,"title":["Once-Daily Dolutegravir\u2013Based Antiretroviral Therapy Among Adults With Advanced HIV Disease Receiving 1 Month of Daily Rifapentine and Isoniazid for Tuberculosis-Preventive Therapy and Fluconazole for Treatment of Cryptococcal Meningitis: Results of a Pharmacokinetic Study"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7009-9144","authenticated-orcid":false,"given":"Jayne","family":"Ellis","sequence":"first","affiliation":[{"name":"Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]},{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2705-108X","authenticated-orcid":false,"given":"Gila","family":"Hale","sequence":"additional","affiliation":[{"name":"Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]},{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5874-3219","authenticated-orcid":false,"given":"Allan","family":"Buzibye","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Omali","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8839-1012","authenticated-orcid":false,"given":"Sandra","family":"Naluyima","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5824-1072","authenticated-orcid":false,"given":"Nathan","family":"Ntenkaire","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J","family":"Nsangi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane Frances","family":"Ndyetukira","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisat","family":"Sadiq","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Ahimbisibwe","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifah","family":"Nabbaale","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1444-8389","authenticated-orcid":false,"given":"Asmus","family":"Tukundane","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9092-9522","authenticated-orcid":false,"given":"Wilber","family":"Bakka","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-4887","authenticated-orcid":false,"given":"Jane","family":"Gakuru","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida N","family":"Kawuma","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona V","family":"Cresswell","sequence":"additional","affiliation":[{"name":"Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]},{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]},{"name":"Global Health and Infection, Brighton and Sussex Medical School , Brighton ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A J","family":"Moore","sequence":"additional","affiliation":[{"name":"Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B","family":"Meya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]},{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]},{"name":"School of Medicine, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Boulware","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0134-5855","authenticated-orcid":false,"given":"Catriona","family":"Waitt","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]},{"name":"Department of Women\u2019s and Children\u2019s Health, Faculty of Health and Life Sciences, University of Liverpool , Liverpool ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph N","family":"Jarvis","sequence":"additional","affiliation":[{"name":"Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]},{"name":"Botswana Harvard Health Partnership , Gaborone ,","place":["Botswana"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5513-5509","authenticated-orcid":false,"given":"Melanie R","family":"Nicol","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"2026081303413205500_ofag415-B1","author":"2020 WHO Global TB report. World Health Organization"},{"key":"2026081303413205500_ofag415-B2","author":"World Health Organization"},{"key":"2026081303413205500_ofag415-B3","article-title":"Treatment of latent tuberculosis infection in HIV infected persons","volume":"2010","author":"Akolo","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"2026081303413205500_ofag415-B4","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1056\/NEJMoa1806808","article-title":"One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis","volume":"380","author":"Swindells","year":"2019","journal-title":"N Engl J Med"},{"key":"2026081303413205500_ofag415-B5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s40262-016-0424-1","article-title":"Comparative clinical pharmacokinetics and pharmacodynamics of HIV-1 integrase strand transfer inhibitors","volume":"56","author":"Podany","year":"2017","journal-title":"Clin Pharmacokinet"},{"key":"2026081303413205500_ofag415-B6","author":"Avihingsanon"},{"key":"2026081303413205500_ofag415-B7","doi-asserted-by":"crossref","first-page":"e422","DOI":"10.1016\/S2352-3018(23)00115-7","article-title":"Dolutegravir once daily with rifampicin for HIV and tuberculosis","volume":"10","author":"Naidoo","year":"2023","journal-title":"Lancet HIV"},{"key":"2026081303413205500_ofag415-B8","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1093\/cid\/ciad730","article-title":"Treatment responses to integrase strand-transfer inhibitor-containing antiretroviral regimens in combination with short-course rifapentine-based regimens for latent tuberculosis infection among people with HIV","volume":"78","author":"Lin","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2026081303413205500_ofag415-B9","doi-asserted-by":"crossref","first-page":"e401","DOI":"10.1016\/S2352-3018(20)30032-1","article-title":"Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients with HIV taking dolutegravir-based antiretroviral therapy: a phase 1\/2 trial","volume":"7","author":"Dooley","year":"2020","journal-title":"Lancet HIV"},{"key":"2026081303413205500_ofag415-B10","first-page":"983","article-title":"Twice-daily dolutegravir-based antiretroviral therapy with 1 month of daily rifapentine and isoniazid for tuberculosis prevention","volume":"79","author":"Podany","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2026081303413205500_ofag415-B11"},{"key":"2026081303413205500_ofag415-B12","author":"M\u00e9decins\u202fSans\u202fFronti\u00e8res"},{"key":"2026081303413205500_ofag415-B13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.12688\/wellcomeopenres.19324.1","article-title":"Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease: a randomised strategy trial","volume":"9","author":"Ellis","year":"2024","journal-title":"Wellcome Open Res"},{"key":"2026081303413205500_ofag415-B14","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1016\/S2352-3018(25)00246-2","article-title":"Inpatient initiation of tuberculosis preventive therapy with 1 month of isoniazid and rifapentine for adults with advanced HIV disease and cryptococcal meningitis (IMPROVE): a non-inferiority, randomised controlled trial","volume":"13","author":"Ellis","year":"2026","journal-title":"Lancet HIV"},{"key":"2026081303413205500_ofag415-B15","author":"Global HIV Prevention Coalition"},{"key":"2026081303413205500_ofag415-B16","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1097\/FTD.0b013e3181b20b40","article-title":"A rapid and sensitive LC-MS\/MS method for determination of fluconazole in human plasma and its application in infants with Candida infections","volume":"31","author":"Wu","year":"2009","journal-title":"Ther Drug Monit"},{"key":"2026081303413205500_ofag415-B17","article-title":"Dolutegravir pharmacokinetics in Ugandan patients with TB and HIV receiving standard- versus high-dose rifampicin","volume":"67","author":"Kengo","year":"2023","journal-title":"Antimicrob. Agents Chemother"},{"key":"2026081303413205500_ofag415-B18","article-title":"Minimum inhibitory concentration distribution of fluconazole against Cryptococcus species and the fluconazole exposure prediction model","volume":"6","author":"Chesdachai","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2026081303413205500_ofag415-B19","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1128\/AAC.00216-13","article-title":"Pharmacokinetics and pharmacodynamics of fluconazole for cryptococcal meningoencephalitis: implications for antifungal therapy and in vitro susceptibility breakpoints","volume":"57","author":"Sudan","year":"2013","journal-title":"Antimicrob. Agents Chemother"},{"key":"2026081303413205500_ofag415-B20","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1093\/jac\/dkad043","article-title":"Population pharmacokinetics of unbound and total dolutegravir concentrations in children aged 12 years and older: a PK substudy of the SMILE trial","volume":"78","author":"Abdalla","year":"2023","journal-title":"J Antimicrob Chemother"},{"key":"2026081303413205500_ofag415-B21","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/FPC.0000000000000562","article-title":"Pharmacogenetics of plasma dolutegravir exposure during 1-month rifapentine\/isoniazid treatment of latent tuberculosis","volume":"35","author":"Covington","year":"2025","journal-title":"Pharmacogenet Genomics"},{"key":"2026081303413205500_ofag415-B22","first-page":"983","article-title":"Twice-daily dolutegravir\u2013based antiretroviral therapy with 1 month of daily rifapentine and isoniazid for tuberculosis prevention","volume":"79","author":"Podany","year":"2024","journal-title":"Clin Infect Dis"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofag415\/68719791\/ofag415.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/13\/8\/ofag415\/68719791\/ofag415.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/13\/8\/ofag415\/68719791\/ofag415.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T07:41:43Z","timestamp":1786606903000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofag415\/8728422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":22,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofag415","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,7,8]]},"article-number":"ofag415"}}