title: Effectiveness of the standard WHO recommended retreatment regimen (category II) for tuberculosis in Kampala, Uganda: a prospective cohort study.
abstract: BACKGROUND
  Each year, 10%-20% of patients with tuberculosis (TB) in low- and middle-income countries present with previously treated TB and are empirically started on a World Health Organization (WHO)-recommended standardized retreatment regimen. The effectiveness of this retreatment regimen has not been systematically evaluated.
  
  
  RESULTS
  From July 2003 to January 2007, we enrolled smear-positive, pulmonary TB patients into a prospective cohort to study treatment outcomes and mortality during and after treatment with the standardized retreatment regimen. Median time of follow-up was 21 months (interquartile range 12-33 months). A total of 29/148 (20%) HIV-uninfected and 37/140 (26%) HIV-infected patients had an unsuccessful treatment outcome. In a multiple logistic regression analysis to adjust for confounding, factors associated with an unsuccessful treatment outcome were poor adherence (adjusted odds ratio [aOR] associated with missing half or more of scheduled doses 2.39; 95% confidence interval (CI) 1.10-5.22), HIV infection (2.16; 1.01-4.61), age (aOR for 10-year increase 1.59; 1.13-2.25), and duration of TB symptoms (aOR for 1-month increase 1.12; 1.04-1.20). All patients with multidrug-resistant TB had an unsuccessful treatment outcome. HIV-infected individuals were more likely to die than HIV-uninfected individuals (p<0.0001). Multidrug-resistant TB at enrollment was the only common risk factor for death during follow-up for both HIV-infected (adjusted hazard ratio [aHR] 17.9; 6.0-53.4) and HIV-uninfected (14.7; 4.1-52.2) individuals. Other risk factors for death during follow-up among HIV-infected patients were CD4<50 cells/ml and no antiretroviral treatment (aHR 7.4, compared to patients with CD4≥200; 3.0-18.8) and Karnofsky score <70 (2.1; 1.1-4.1); and among HIV-uninfected patients were poor adherence (missing half or more of doses) (3.5; 1.1-10.6) and duration of TB symptoms (aHR for a 1-month increase 1.9; 1.0-3.5).
  
  
  CONCLUSIONS
  The recommended regimen for retreatment TB in Uganda yields an unacceptable proportion of unsuccessful outcomes. There is a need to evaluate new treatment strategies in these patients.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston University Medical School, Boston, Massachusetts, USA. edward.jones@bmc.org
authors.forename: Edward C
authors.initials: EC
authors.lastname: Jones-López
authors.forename: Irene
authors.initials: I
authors.lastname: Ayakaka
authors.forename: Jonathan
authors.initials: J
authors.lastname: Levin
authors.forename: Nancy
authors.initials: N
authors.lastname: Reilly
authors.forename: Francis
authors.initials: F
authors.lastname: Mumbowa
authors.forename: Scott
authors.initials: S
authors.lastname: Dryden-Peterson
authors.forename: Grace
authors.initials: G
authors.lastname: Nyakoojo
authors.forename: Kevin
authors.initials: K
authors.lastname: Fennelly
authors.forename: Beth
authors.initials: B
authors.lastname: Temple
authors.forename: Susan
authors.initials: S
authors.lastname: Nakubulwa
authors.forename: Moses L
authors.initials: ML
authors.lastname: Joloba
authors.forename: Alphonse
authors.initials: A
authors.lastname: Okwera
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Eisenach
authors.forename: Ruth
authors.initials: R
authors.lastname: McNerney
authors.forename: Alison M
authors.initials: AM
authors.lastname: Elliott
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
authors.forename: Peter G
authors.initials: PG
authors.lastname: Smith
authors.forename: Roy D
authors.initials: RD
authors.lastname: Mugerwa
mesh_terms: D000328:Adult; D000367:Age Factors; D000995:Antitubercular Agents / Q000592:standards* / Q000627:therapeutic use*; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology; D006801:Humans; D016015:Logistic Models; D008297:Male; D017410:Practice Guidelines as Topic; D015995:Prevalence; D011446:Prospective Studies; D019233:Retreatment / Q000941:ethics; D017211:Treatment Failure; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000401:mortality*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000401:mortality*; D014454:Uganda / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents