title: Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Culture-positive treatment failure or relapse.
  
  
  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.
authors.affiliation: Denver Public Health, Denver, CO 80204, USA. bburman@dhha.org
authors.forename: William
authors.initials: W
authors.lastname: Burman
authors.forename: Debra
authors.initials: D
authors.lastname: Benator
authors.forename: Andrew
authors.initials: A
authors.lastname: Vernon
authors.forename: Awal
authors.initials: A
authors.lastname: Khan
authors.forename: Brenda
authors.initials: B
authors.lastname: Jones
authors.forename: Claudia
authors.initials: C
authors.lastname: Silva
authors.forename: Chris
authors.initials: C
authors.lastname: Lahart
authors.forename: Stephen
authors.initials: S
authors.lastname: Weis
authors.forename: Barbara
authors.initials: B
authors.lastname: King
authors.forename: Bonita
authors.initials: B
authors.lastname: Mangura
authors.forename: Marc
authors.initials: M
authors.lastname: Weiner
authors.forename: Wafaa
authors.initials: W
authors.lastname: El-Sadr
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017828:Rifabutin / Q000008:administration & dosage*; D017211:Treatment Failure; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D044966:Anti-Retroviral Agents; D000904:Antibiotics, Antitubercular; D017828:Rifabutin