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We report the pharmacokinetics of rifampin, isoniazid, and pyrazinamide in a cohort of patients being treated for active tuberculosis, the majority of whom were coinfected with HIV-1 and had commenced antiretroviral therapy within 2 months of starting antituberculosis treatment. We also examined the association between antituberculosis drug concentrations and reported drug side effects at the 2-month clinical review. One hundred patients with pulmonary tuberculosis (65% coinfected with HIV-1) were intensively sampled to determine rifampin, isoniazid, and pyrazinamide plasma concentrations after 7 to 8 weeks of a daily quadruple-therapy regimen dosed according to World Health Organization (WHO) weight bands. Pharmacokinetic parameters were determined for each patient by using nonlinear mixed-effects models. HIV-1-coinfected patients had lower clearance rates for rifampin (21% decrease) and isoniazid (23% decrease) than HIV-1-uninfected patients, with resulting higher areas under the concentration-time curve from 0 to 24 h (AUC<jats:sub>0\u201324<\/jats:sub>) and maximum concentrations of drug in serum (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>). Antiretroviral therapy (ART) that included double-standard-dose lopinavir\/ritonavir further lowered rifampin clearance, by 46%, and increased the AUC<jats:sub>0\u201324<\/jats:sub>. The current uniform dosing (per kilogram of body weight) across WHO weight bands was associated with a trend of decreased pharmacokinetic exposures for the lowest weight band. Use of fat-free mass as opposed to total body weight for allometric scaling of clearance significantly improved the model. Ambulant HIV-1-coinfected patients, the majority of whom were coprescribed ART, did not have reduced antituberculosis drug concentrations compared to HIV-1-uninfected patients.<\/jats:p>","DOI":"10.1128\/aac.00480-16","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T03:04:34Z","timestamp":1470107074000},"page":"6050-6059","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["HIV-1 Coinfection Does Not Reduce Exposure to Rifampin, Isoniazid, and Pyrazinamide in South African Tuberculosis Outpatients"],"prefix":"10.1128","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7830-1394","authenticated-orcid":false,"given":"Neesha","family":"Rockwood","sequence":"first","affiliation":[{"name":"Department of Medicine, Imperial College, London, United Kingdom"},{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme","family":"Meintjes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Imperial College, London, United Kingdom"},{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxwell","family":"Chirehwa","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lubbe","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"McIlleron","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Imperial College, London, United Kingdom"},{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Francis Crick Institute Mill Hill Laboratory, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Global tuberculosis report 2015","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 2015. 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