1423 Pharmacogenomics (2014) 15(11), 1423–1435 ISSN 1462-2416 part of Pharmacogenomics Research Article 10.2217/PGS.14.73 © 2014 Future Medicine Ltd Aim: We investigated the effects of rifampicin-based anti-TB treatment on plasma efavirenz exposure and the implications of CYP2B6 genotype. Patients & methods: Antiretroviral therapy-naive Ugandan HIV patients without (n = 157) or with TB coinfection (n = 106) were enrolled and treated with efavirenz-based highly active antiretroviral therapy alone or with rifampicin-based anti-TB therapy, respectively. Efavirenz plasma concentration was determined on day 3 and weeks 1, 2, 8, 12, 16, 20, 24, 28 and 32. Results: Rifampicin-based anti-TB cotreatment reduced plasma efavirenz exposure during the first 2 weeks (p < 0.05), but no significant effect was observed afterwards. Although not significant, rifampicin-based anti-TB cotreatment inconsistently increased efavirenz exposure over time, which was reduced immediately after completing anti-TB therapy. CYP2B6*6, *11 and ABCB1 c.4036A>G genotypes were significant predictors of efavirenz plasma exposure. Conclusion: Plasma efavirenz exposure is mainly influenced by CYP2B6 genotype, but not by rifampicin cotreatment. Therefore, no efavirenz dosage adjustment during rifampicin cotreatment is required in Ugandans. Original submitted 3 March 2014; Revision submitted 7 May 2014 Keywords: ABCB1฀•฀CYP2B6฀•฀efavirenz฀•฀HIV฀•฀induction฀•฀inhibition฀•฀isoniazid฀ •฀pharmacokinetics฀•฀rifampicin฀•฀Ugandans TB remains the most frequently encoun- tered comorbidity among HIV-infected patients, particularly in sub-Saharan Africa. Currently, rifamycins constitute a corner- stone of anti-TB therapy [1] . Efavirenz is the recommended first choice non-nucleoside reverse transcriptase inhibitor for TB–HIV patients cotreated with rifampicin [2] . How- ever, the use of rifamycins in patients who are cotreated with antiretroviral therapy (ART) is marred by drug–drug inter- actions [3] , which are caused by induction and/or inhibition of the activity of the CYP enzymes and the transporter protein, P-gp. Among the rifamycins, rifampicin is the most potent inducer of both CYP enzymes and P-gp; data from Lopez-Cortes et al. in 2002 revealed a reduction in the efavirenz maximum concentration and area under the concentration–time curve of approximately 25% [4] . Using pharmacokinetic simula- tion of nonclinical data in order to predict human efavirenz exposure in healthy vol- unteers, another study suggested increasing the dose of efavirenz during concomitant rifampicin treatment [5] . By contrast, studies from diverse populations – mainly black and Asian populations – reported an insignifi- cant effect of rifampicin on efavirenz plasma concentration, or even increased plasma efavirenz concentrations during rifampicin cotreatment [6–13] . Such varying reports from different efa- virenz–rifampicin interaction pharmaco- kinetics studies resulted in inconsistent recommendations from different TB–HIV treatment guidelines. The International Anti- viral Society-USA panel and the British HIV CYP2B6 genotype, but not rifampicin-based anti-TB cotreatments, explains variability in long-term efavirenz plasma exposure Jackson K Mukonzo 1,2 , Sarah Nanzigu 1,2 , Paul Waako 1 , Jasper Ogwal-Okeng 1 , Lars L Gustafson 1 & Eleni Aklillu* ,1 1 Division฀of฀Clinical฀Pharmacology,฀ Department฀of฀Laboratory฀Medicine,฀ Karolinska฀Institutet,฀Karolinska฀ University฀Hospital฀Huddinge,฀C-168฀ SE-141฀86฀Stockholm,฀Sweden 2 Department฀of฀Pharmacology฀&฀ Therapeutics,฀College฀of฀Health฀Sciences,฀ Makerere฀University,฀Uganda *Author฀for฀correspondence:฀ Tel.:฀+46฀8฀5858฀7882฀ Fax:฀+46฀8฀5858฀1070฀ eleni.aklillu@ki.se For reprint orders, please contact: reprints@futuremedicine.com