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

• DOI: 10.1164/rccm.200503-417oc
• Publication Date: 2005-08-19T00:45:00Z
• Authors: William Burman; Debra Benator; Andrew Vernon; Awal Khan; Brenda Jones; Claudia Silva; Chris Lahart; Stephen Weis; Barbara King; Bonita Mangura; Marc Weiner; Wafaa El-Sadr
• Keywords: Adult; Male; 0301 basic medicine; AIDS-Related Opportunistic Infections; Middle Aged; Drug Administration Schedule; 3. Good health; 03 medical and health sciences; Treatment Outcome; Anti-Retroviral Agents; Rifabutin; Drug Resistance, Bacterial; Humans; Drug Therapy, Combination; Female; Prospective Studies; Treatment Failure; Antibiotics, Antitubercular; Tuberculosis, Pulmonary

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.To evaluate the activity of intermittent rifabutin-based therapy.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.Culture-positive treatment failure or relapse.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.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.