Delayed Sputum Culture Conversion in Tuberculosis-Human Immunodeficiency Virus-Coinfected Patients with Low Isoniazid and Rifampicin Concentrations

Christine Sekaggya-Wiltshire, Amrei Von Braun, Mohammed Lamorde, Bruno Ledergerber, Allan Buzibye, Lars Henning, Joseph Musaazi, Ursula Gutteck, Paolo Denti, Mini De Kock, Alexander Jetter, Pauline Byakika-Kibwika, Nadia Eberhard, Joshua Matovu, Moses Joloba, Daniel Muller, Yukari C. Manabe, Moses R. Kamya, Natascia Corti, Andrew KambuguBarbara Castelnuovo, Jan S. Fehr

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)708-716
Number of pages9
JournalClinical Infectious Diseases
Volume67
Issue number5
DOIs
StatePublished - Aug 16 2018

Keywords

  • Tuberculosis
  • anti-tuberculosis drugs.
  • outcomes
  • pharmacokinetics

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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