{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:39:44Z","timestamp":1791725984297,"version":"4.3.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2009,11,1]],"date-time":"2009-11-01T00:00:00Z","timestamp":1257033600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:p>Coadministration of antitubercular and antiretroviral therapy is common in high-burden countries where tuberculosis is the commonest opportunistic infection. Concomitant use of rifampicin and many antiretroviral drugs is complicated by drug\u2013drug interactions caused by the potent induction by rifampicin of genes involved in drug metabolism and transport, which could result in sub-therapeutic antiretroviral drug concentrations. This review focuses on drug\u2013drug interactions involving antiretrovirals used in resource-limited settings: the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz or nevirapine, and ritonavir-boosted protease inhibitors. The reduction of nevirapine concentrations with concomitant rifampicin is greater than with efavirenz, particularly during the lead-in dose period when subtherapeutic concentrations occur in the majority of patients. There is reassuring data on the effectiveness of standard doses of efavirenz with concomitant rifampicin, but the largest cohort study found a higher risk of virological failure with nevirapine. The drug\u2013drug interaction between rifampicin and ritonavir-boosted protease inhibitors is more marked than with the NNRTIs, and therapeutic concentrations have only been achieved with adjusted doses of lopinavir\/ ritonavir or with saquinavir\/ritonavir (400\/400 mg every 12 h). The major barrier to using adjusted dose protease inhibitors with rifampicin is the high rates of hepatotoxicity seen in healthy volunteers. The alternative strategy followed in resource-rich settings is to replace rifampicin with rifabutin, but even if the price of rifabutin were to be dramatically reduced it would be difficult to implement in high-burden countries where standardized antitubercular regimens with fixed-dose combinations are used.<\/jats:p>","DOI":"10.3851\/imp1455","type":"journal-article","created":{"date-parts":[[2009,12,3]],"date-time":"2009-12-03T10:01:14Z","timestamp":1259834474000},"page":"1039-1043","source":"Crossref","is-referenced-by-count":47,"title":["Effectiveness and Safety of Antiretrovirals with Rifampicin: Crucial Issues for High-Burden Countries"],"prefix":"10.1177","volume":"14","author":[{"given":"Gary","family":"Maartens","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Decloedt","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2009,11,1]]},"reference":[{"key":"bibr1-IMP1455","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68383-9"},{"key":"bibr2-IMP1455","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342090-00003"},{"key":"bibr3-IMP1455","unstructured":"World Health Organization. Scaling up antiretroviral therapy in resource-limited settings: treatment guidelines for a public health approach. 2006 Revision. Geneva: World Health Organization 2006."},{"key":"bibr4-IMP1455","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.382-392.2001"},{"key":"bibr5-IMP1455","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0022-3565(24)29202-8","volume":"299","author":"Rae J.M.","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"bibr6-IMP1455","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm484"},{"key":"bibr7-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-200112150-00007"},{"key":"bibr8-IMP1455","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1177\/135965350501000809","volume":"10","author":"Autar R.S.","year":"2005","journal-title":"Antivir Ther"},{"key":"bibr9-IMP1455","doi-asserted-by":"publisher","DOI":"10.1086\/510078"},{"key":"bibr10-IMP1455","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-008-0481-y"},{"key":"bibr11-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000214808.75594.73"},{"key":"bibr12-IMP1455","first-page":"4","volume":"3","author":"La Porte C.J.","year":"2006","journal-title":"Reviews in Antiviral Therapy"},{"key":"bibr13-IMP1455","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1177\/135965350701200406","volume":"12","author":"van Oosterhout J.J.","year":"2007","journal-title":"Antivir Ther"},{"key":"bibr14-IMP1455","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1177\/135965350801300414","volume":"13","author":"Avihingsanon A.","year":"2008","journal-title":"Antivir Ther"},{"key":"bibr15-IMP1455","unstructured":"Sustiva\n                      \u00ae\n                      (efavirenz). Package insert 2009. Bristol\u2013Myers Squibb Princeton, NJ, USA."},{"key":"bibr16-IMP1455","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1177\/135965350801300507","volume":"13","author":"Stohr W.","year":"2008","journal-title":"Antivir Ther"},{"key":"bibr17-IMP1455","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241090-00004"},{"key":"bibr18-IMP1455","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1177\/135965350901400502","volume":"14","author":"Cohen K.","year":"2009","journal-title":"Antivir Ther"},{"key":"bibr19-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31819c33a3"},{"key":"bibr20-IMP1455","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00899-08"},{"key":"bibr21-IMP1455","unstructured":"Centers for Disease Control and Prevention. Managing drug interactions in the treatment of HIV-related tuberculosis. 2007. (Updated December 2007. Accessed 25 March 2009.) Available from http:\/\/www.cdc.gov\/tb\/TB_HIV_DRugs\/default.htm."},{"key":"bibr22-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000183630.27665.30"},{"key":"bibr23-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31817c1ed0"},{"key":"bibr24-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/01213011-200512000-00004"},{"key":"bibr25-IMP1455","first-page":"360","volume":"13","author":"Shipton L.K.","year":"2009","journal-title":"Int J Tuberc Lung Dis"},{"key":"bibr26-IMP1455","doi-asserted-by":"publisher","DOI":"10.1001\/jama.300.5.530"},{"key":"bibr27-IMP1455","doi-asserted-by":"publisher","DOI":"10.1086\/506362"},{"key":"bibr28-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3281532b31"},{"key":"bibr29-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328310407e"},{"key":"bibr30-IMP1455","doi-asserted-by":"publisher","DOI":"10.1086\/599114"},{"key":"bibr31-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32814e6b08"},{"key":"bibr32-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000279711.54922.f0"},{"key":"bibr33-IMP1455","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1293.2008.00597.x"},{"key":"bibr34-IMP1455","first-page":"24","volume":"58","author":"Centers for Disease Control and Prevention.","year":"2009","journal-title":"MMWR"},{"key":"bibr35-IMP1455","first-page":"CD005159","volume":"4","author":"Davies G.","year":"2007","journal-title":"Cochrane Database Syst Rev"},{"key":"bibr36-IMP1455","doi-asserted-by":"publisher","DOI":"10.1086\/313548"},{"key":"bibr37-IMP1455","doi-asserted-by":"publisher","DOI":"10.2165\/00044011-200626080-00005"},{"key":"bibr38-IMP1455","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1553-1560.2004"},{"key":"bibr39-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181642257"},{"key":"bibr40-IMP1455","doi-asserted-by":"crossref","unstructured":"McIlleron H., Ren Y., Nuttall J. Double-dose lopinavir\/ ritonavir provides insufficient lopinavir exposure in children receiving rifampicin-based anti-TB treatment.\n                      16th Conference on Retroviruses and Opportunistic Infections\n                      . 8\u201311 February 2009, Montreal, QC, Canada. Abstract 98.","DOI":"10.3851\/IMP1757"},{"key":"bibr41-IMP1455","unstructured":"Grange S., Schutz M., Riek M. Gaudeul-Ehrhart. Unexpected hepatotoxicity observed in a healthy volunteer study on the effects of multiple dose rifampicin on the steady-state pharmacokinetics of ritonavir-boosted sequinavir and vice versa.\n                      6th International Workshop on Clinical Pharmacology of HIV therapy.\n                      28\u201330 April 2005, Montreal, QC, Canada. Abstract 35."},{"key":"bibr42-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282faa71e"},{"key":"bibr43-IMP1455","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e318189a7df"},{"key":"bibr44-IMP1455","doi-asserted-by":"publisher","DOI":"10.1086\/422724"},{"key":"bibr45-IMP1455","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-137-8-200210150-00007"},{"key":"bibr46-IMP1455","first-page":"276","volume":"9","author":"Tortajada C.","year":"2005","journal-title":"Int J Tuberc Lung Dis"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1455","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1455","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:49:12Z","timestamp":1777380552000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP1455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2009,11]]}},"alternative-id":["10.3851\/IMP1455"],"URL":"https:\/\/doi.org\/10.3851\/imp1455","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11]]}}}