Published ahead of print on August 18, 2005, doi:10.1164/rccm.200503-417OC
Am. J. Respir. Crit. Care Med., Volume 173, Number 3, February 2006, 350-356
A more recent version of this article appeared on February 1, 2006
Submitted on March 16, 2005
Accepted on August 18, 2005
Acquired Rifamycin-resistance with Twice-weekly Treatment of HIV-related Tuberculosis
William Burman1*, Debra Benator2, Andrew Vernon3, Awal Khan3, Brenda Jones4, Claudia Silva4, Chris Lahart5, Stephen Weis6, Barbara King6, Bonita Mangura7, Marc Weiner8, and Wafaa El-Sadr9
1 Denver Public Health, Denver, CO, USA; University of Colorado Health Sciences Center, Denver, CO, USA,
2 Veterans Affairs Medical Center, Washington, DC, USA; George Washington University Medical Center, Washington, DC, USA,
3 Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA,
4 Los Angeles County - University of Southern California Medical Center, Los Angeles, CA, USA,
5 Baylor College of Medicine, Houston, TX, USA,
6 Tarrant County Public Health Department, Fort Worth, TX, USA; University of North Texas Health Sciences Center, Fort Worth, TX, USA,
7 University of Medicine and Dentistry of New Jersey-New Jersey Medical School National Tuberculosis Center, Newark, NJ, USA,
8 University of Texas Health Science Center, San Antonio, TX, USA; South Texas Veterans Health Care System, San Antonio, TX, USA,
9 Harlem Hospital Center, New York, NY, USA; Columbia University College of Physicians and Surgeons, New York, NY, USA
* To whom correspondence should be addressed. E-mail: BBurman{at}dhha.org.
Rationale Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis 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 tuberculosis were treated under direct supervision with 2 months of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly or twice-weekly per the local tuberculosis control program), followed by 4 months of twice-weekly rifabutin plus isoniazid.
Measurements Culture-positive treatment failure or relapse.
Main results 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 9 (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 vs. 0% (0/65, 95% confidence interval, 0.0 - 4.5%) among those with higher CD4 lymphocyte counts (p<0.01). 137 (81%) patients received antiretroviral therapy during tuberculosis treatment. Adverse events were common, but only 2 patients (1%) permanently discontinued study drugs.
Conclusions Intermittent rifabutin-based therapy for HIV-related tuberculosis 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: HIV, tuberculosis, rifabutin, rifamycin-resistance, antiretroviral therapy
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