{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:24:10Z","timestamp":1791329050730,"version":"4.3.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership-2","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["TMA2016CDF-1580"],"award-info":[{"award-number":["TMA2016CDF-1580"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000360","name":"Scottish Funding Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000360","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000740","name":"University of St. Andrews","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000740","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Higher doses of rifampicin may improve treatment outcomes and reduce the duration of tuberculosis (TB) therapy. However, drug\u2013drug interactions with antiretroviral therapy (ART) and safety in people with human immunodeficiency virus (HIV) have not been evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a randomized, open-label trial where newly diagnosed TB patients were randomized to higher (35 mg\/kg) or standard (10 mg\/kg) daily-dose rifampicin. ART treatment\u2013naive patients were randomized to dolutegravir- or efavirenz-based ART. At week 6, trough dolutegravir or mid-dose efavirenz plasma concentrations were assayed. HIV viral load was measured at week 24.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 128 patients randomized, the median CD4 count was 191 cells\/mm3. The geometric mean ratio (GMR) for trough dolutegravir concentrations on higher- vs standard-dose rifampicin was 0.57 (95% confidence interval [CI], .34\u2013.97; P = .039) and the GMR for mid-dose efavirenz was 0.63 (95% CI, .38\u20131.07; P = .083). There was no significant difference in attainment of targets for dolutegravir trough or efavirenz mid-dose concentrations between rifampicin doses. The incidence of HIV treatment failure at week 24 was similar between rifampicin doses (14.9% vs 14.0%, P = .901), as was the incidence of drug-related grade 3\u20134 adverse events (9.8% vs 6%). At week 8, fewer patients remained sputum culture positive on higher-dose rifampicin (18.6% vs 37.0%, P = .063).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Compared with standard-dose rifampicin, high-dose rifampicin reduced dolutegravir and efavirenz exposures, but HIV suppression was similar across treatment arms. Higher-dose rifampicin was well tolerated among people with HIV and associated with a trend toward faster sputum culture conversion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT03982277.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac585","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T11:39:58Z","timestamp":1658403598000},"page":"e910-e919","source":"Crossref","is-referenced-by-count":24,"title":["Decreased Dolutegravir and Efavirenz Concentrations With Preserved Virological Suppression in Patients With Tuberculosis and Human Immunodeficiency Virus Receiving High-Dose Rifampicin"],"prefix":"10.1093","volume":"76","author":[{"given":"Christine","family":"Sekaggya-Wiltshire","sequence":"first","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"},{"name":"Department of Medicine, Mulago National Referral Hospital , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Nabisere","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Musaazi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Otaalo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Aber","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Alinaitwe","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliet","family":"Nampala","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letisha","family":"Najjemba","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Buzibye","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Omali","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamunkhwala","family":"Gausi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Clinical Pharmacology, University of Cape Town , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Kengo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Clinical Pharmacology, University of Cape Town , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Lamorde","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences , Kampala , 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