Published ahead of print on August 18, 2005, doi:10.1164/rccm.200503-417OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200503-417OC
Acquired Rifamycin Resistance with Twice-Weekly Treatment of HIV-related TuberculosisDenver Public Health; University of Colorado Health Sciences Center, Denver, Colorado; Veterans Affairs Medical Center of Washington, DC; George Washington University Medical Center, Washington, DC; Centers for Disease Control and Prevention, Atlanta, Georgia; Los Angeles County–University of Southern California Medical Center, Los Angeles, California; Baylor College of Medicine, Houston; Tarrant County Public Health Department; University of North Texas Health Sciences Center, Fort Worth; University of Texas Health Science Center; South Texas Veterans Health Care System, San Antonio, Texas; University of Medicine and Dentistry of New Jersey–New Jersey Medical School National Tuberculosis Center, Newark, New Jersey; Harlem Hospital Center; and Columbia University College of Physicians and Surgeons, New York, New York Correspondence and requests for reprints should be addressed to William Burman, M.D., Denver Public Health, 605 Bannock Street, Denver, CO 80204. E-mail: bburman{at}dhha.org 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. Conclusions: Intermittent rifabutin-based therapy for HIV-related TB was well tolerated, but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts.
Key Words: antiretroviral therapy • HIV • rifabutin • rifamycin resistance • tuberculosis This article has been cited by other articles:
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