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

Background The relationship between concentrations of anti-tuberculosis (TB) drugs, sputum conversion and treatment outcome remains unclear. We sought to determine the association between anti-TB drug concentrations and sputum conversion among TB-HIV co-infected patients on first-line anti-TB drugs. Method We enrolled HIV-infected Ugandans with pulmonary TB. Estimation of first-line anti-TB drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of TB 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 TB treatment or by the end of follow-up; Hazard ratio (HR) 0.54: 95% confidence interval (CI): 0.37-0.77, P=0.001 and HR: 0.61, 95% CI: 0.44-0.85, P=0.003, respectively. Patients in the highest AUC quartile for rifampicin and isoniazid were approximately two times more likely to experience sputum conversion. Rifampicin and isoniazid concentrations below the thresholds and being in a weight band <55kg were both risk factors for unfavorable TB treatment outcomes. Only 4.4% of the participants had treatment failure. Conclusion Although low anti-TB 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 on TB transmission.