Delayed sputum culture conversion in tuberculosis-human immunodeficiency virus-coinfected patients with low isoniazid and rifampicin concentrations

Sekaggya-Wiltshire, Christine, von Braun, Amrei, Lamorde, Mohammed, Ledergerber, Bruno, Buzibye, Allan, Henning, Lars, Musaazi, Joseph, Gutteck, Ursula, Denti, Paolo, de Kock, Miné, Jetter, Alexander, Byakika-Kibwika, Pauline, Eberhard, Nadia, Matovu, Joshua, Joloba, Moses, Muller, Daniel, Manabe, Yukari C., Kamya, Moses R., Corti, Natascia, Kambugu, Andrew, Castelnuovo, Barbara, and Fehr, Jan S. (2018) Delayed sputum culture conversion in tuberculosis-human immunodeficiency virus-coinfected patients with low isoniazid and rifampicin concentrations. Clinical Infectious Diseases, 67 (5). pp. 708-716.

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Background. The relationship between concentrations of antituberculosis drugs, sputum culture conversion, and treatment outcome remains unclear. We sought to determine the association between antituberculosis drug concentrations and sputum conversion among patients coinfected with tuberculosis and human immunodeficiency virus (HIV) and receiving first-line antituberculosis drugs.

Methods. We enrolled HIV-infected Ugandans with pulmonary tuberculosis. Estimation of first-line antituberculosis drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of tuberculosis treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion.

Results. We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of tuberculosis treatment (hazard ratio, 0.54; 95% confidence interval, .37–.77; P = .001) or by the end of follow-up (0.61; .44–.85; P = .003). Patients in the highest quartile for area under the rifampicin and isoniazid concentration-time curves for were twice as likely to experience sputum conversion than those in the lowest quartile. Rifampicin and isoniazid concentrations below the thresholds and weight <55 kg were both risk factors for unfavorable tuberculosis treatment outcomes. Only 4.4% of the participants had treatment failure.

Conclusion. Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission.

Item ID: 55573
Item Type: Article (Research - C1)
ISSN: 1537-6591
Keywords: tuberculosis, outcomes, pharmacokinetics, anti-tuberculosis drugs
Copyright Information: © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Funders: Infectious Disease Institute (IDI), University of Zurich, Medical Education Partnership Initiative
Projects and Grants: Medical Education Partnership Initiative grant 5R24TW008886
Date Deposited: 12 Sep 2018 09:35
FoR Codes: 42 HEALTH SCIENCES > 4203 Health services and systems > 420399 Health services and systems not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920499 Public Health (excl. Specific Population Health) not elsewhere classified @ 100%
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