Effectiveness of the standard WHO recommended retreatment regimen (Category II) for tuberculosis in Kampala, Uganda: A prospective cohort study

Edward C. Jones-López, Irene Ayakaka, Jonathan Levin, Nancy Reilly, Francis Mumbowa, Scott Dryden-Peterson, Grace Nyakoojo, Kevin Fennelly, Beth Temple, Susan Nakubulwa, Moses L. Joloba, Alphonse Okwera, Kathleen D. Eisenach, Ruth McNerney, Alison M. Elliott, Jerrold J. Ellner, Peter G. Smith, Roy D. Mugerwa

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    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.

    Methods and Findings: 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 enrolment 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.

    Original languageEnglish
    Article numbere1000427
    Pages (from-to)1-11
    Number of pages11
    JournalPLoS Medicine
    Volume8
    Issue number3
    DOIs
    Publication statusPublished - 15 Mar 2011

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