Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis

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

Research output: Contribution to journalArticleResearchpeer-review

123 Citations (Scopus)

Abstract

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 HIVRNA 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/mm 3 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.

Original languageEnglish
Pages (from-to)350-356
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume173
Issue number3
DOIs
StatePublished - 1 Feb 2006

Fingerprint

Rifabutin
Tuberculosis
HIV
CD4 Lymphocyte Count
Treatment Failure
Recurrence
Isoniazid
Therapeutics
Confidence Intervals
Pyrazinamide
Ethambutol
Rifampin
rifamycin SV
Prospective Studies
Pharmaceutical Preparations

Keywords

  • Antiretroviral therapy
  • HIV
  • Rifabutin
  • Rifamycin resistance
  • Tuberculosis

Cite this

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. / Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis. In: American Journal of Respiratory and Critical Care Medicine. 2006 ; Vol. 173, No. 3. pp. 350-356.
@article{22f1f6a6510e4a8da4d0eaf0ad98524e,
title = "Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis",
abstract = "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 HIVRNA 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/mm 3 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.",
keywords = "Antiretroviral therapy, HIV, Rifabutin, Rifamycin resistance, Tuberculosis",
author = "William Burman and Debra Benator and Andrew Vernon and Awal Khan and Brenda Jones and Claudia Silva and Chris Lahart and Stephen Weis and Barbara King and Bonita Mangura and Marc Weiner and Wafaa El-Sadr",
year = "2006",
month = "2",
day = "1",
doi = "10.1164/rccm.200503-417OC",
language = "English",
volume = "173",
pages = "350--356",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "3",

}

Burman, W, Benator, D, Vernon, A, Khan, A, Jones, B, Silva, C, Lahart, C, Weis, S, King, B, Mangura, B, Weiner, M & El-Sadr, W 2006, 'Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis', American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 3, pp. 350-356. https://doi.org/10.1164/rccm.200503-417OC

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.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 173, No. 3, 01.02.2006, p. 350-356.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis

AU - Burman, William

AU - Benator, Debra

AU - Vernon, Andrew

AU - Khan, Awal

AU - Jones, Brenda

AU - Silva, Claudia

AU - Lahart, Chris

AU - Weis, Stephen

AU - King, Barbara

AU - Mangura, Bonita

AU - Weiner, Marc

AU - El-Sadr, Wafaa

PY - 2006/2/1

Y1 - 2006/2/1

N2 - 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 HIVRNA 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/mm 3 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.

AB - 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 HIVRNA 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/mm 3 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.

KW - Antiretroviral therapy

KW - HIV

KW - Rifabutin

KW - Rifamycin resistance

KW - Tuberculosis

UR - http://www.scopus.com/inward/record.url?scp=32144435415&partnerID=8YFLogxK

U2 - 10.1164/rccm.200503-417OC

DO - 10.1164/rccm.200503-417OC

M3 - Article

VL - 173

SP - 350

EP - 356

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 3

ER -