Acquired Rifamycin Resistance with Twice-Weekly Treatment of HIV-related Tuberculosis

Burman, William; Benator, Debra; Vernon, Andrew; Khan, Awal; Jones, Brenda; Silva, Claudia; Lahart, Chris; Weis, Stephen; King, Barbara; Mangura, Bonita; Weiner, Marc; El-Sadr, Wafaa Mahmoud; Tuberculosis Trials Consortium

Rationale: Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study.

Objective: To evaluate the activity of intermittent rifabutin-based therapy.

Methods: Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid.

Measurements: Culture-positive treatment failure or relapse.

Main Results: A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 (interquartile range, 35–175) and 5.3 log10 copies/ml (interquartile range, 4.8–5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5–22.0%) among patients with CD4 < 100 cells/mm3 versus 0% (0/65; 95% confidence interval, 0.0–4.5%) among those with higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs.


Also Published In

American Journal of Respiratory and Critical Care Medicine

More About This Work

Academic Units
American Thoracic Society
Published Here
October 16, 2015