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In a longitudinal cohort study, we evaluated the effects of efavirenz\/rifampicin co\u2010treatment and time of ART initiation on CYP3A induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Treatment\u2010na\u00efve TB\u2010HIV co\u2010infected patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a0102) were randomized to efavirenz\u2010based\u2010ART after 4 (<jats:italic>n<\/jats:italic>\u00a0=\u00a069) or 8\u00a0weeks (<jats:italic>n<\/jats:italic>\u00a0=\u00a033) of commencing rifampicin\u2010based anti\u2010TB therapy. HIV patients without TB (<jats:italic>n<\/jats:italic>\u00a0=\u00a094) receiving efavirenz\u2010based\u2010ART only were enrolled as control. Plasma 4\u03b2\u2010hydroxycholesterol\/cholesterol (4\u03b2\u2010OHC\/Chol) ratio, an endogenous biomarker for CYP3A activity, was determined at baseline, at 4 and 16\u00a0weeks of ART.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In patients treated with efavirenz only, median 4\u03b2\u2010OHC\/Chol ratios increased from baseline by 269% and 275% after 4 and 16\u00a0weeks of ART, respectively. In TB\u2010HIV patients, rifampicin only therapy for 4 and 8 weeks increased median 4\u03b2\u2010OHC\/Chol ratios from baseline by 378% and 576% respectively. After efavirenz\/rifampicin co\u2010treatment, 4\u03b2\u2010OHC\/Chol ratios increased by 560% of baseline (4 weeks) and 456% of baseline (16 weeks). Neither time of ART initiation, sex, genotype nor efavirenz plasma concentration were significant predictors of 4\u03b2\u2010OHC\/Chol ratios after 4 weeks of efavirenz\/rifampicin co\u2010treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Rifampicin induced CYP3A more potently than efavirenz, with maximum induction occurring within the first 4\u00a0weeks of rifampicin therapy. We provide pharmacological evidence that early (4\u00a0weeks) or deferred (8\u00a0weeks) ART initiation during anti\u2010TB therapy has no significant effect on CYP3A induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v178.16\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v178.16\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15309","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T12:49:12Z","timestamp":1604666952000},"page":"3294-3308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Early or deferred initiation of efavirenz during rifampicin\u2010based TB therapy has no significant effect on CYP3A induction in TB\u2010HIV infected patients"],"prefix":"10.1111","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9788-0790","authenticated-orcid":false,"given":"Eleni","family":"Aklillu","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, 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