title: Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study.
abstract: BACKGROUND
  Data from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes.
  
  
  METHODS
  In a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes-mortality and culture conversion.
  
  
  RESULTS
  195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0.13). Treatment with moxifloxacin (hazard ratio 0.11, 95% CI 0.01-0.82; p=0.03), previous culture-proven multidrug-resistant tuberculosis (5.21, 1.93-14.1; p=0.001), and number of drugs used in a regimen (0.59, 0.45-0.78, p<0.0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0.38, 0.18-0.80; p=0.01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment.
  
  
  CONCLUSIONS
  In South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity.
  
  
  BACKGROUND
  South African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership.
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, Cape Town, South Africa. keertan.dheda@uct.ac.za
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
authors.forename: Karen
authors.initials: K
authors.lastname: Shean
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.forename: Motasim
authors.initials: M
authors.lastname: Badri
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Streicher
authors.forename: Liesl
authors.initials: L
authors.lastname: Page-Shipp
authors.forename: Paul
authors.initials: P
authors.lastname: Willcox
authors.forename: Melanie-Anne
authors.initials: MA
authors.lastname: John
authors.forename: Gary
authors.initials: G
authors.lastname: Reubenson
authors.forename: Darshini
authors.initials: D
authors.lastname: Govindasamy
authors.forename: Michelle
authors.initials: M
authors.lastname: Wong
authors.forename: Xavier
authors.initials: X
authors.lastname: Padanilam
authors.forename: Alicia
authors.initials: A
authors.lastname: Dziwiecki
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Sweetness
authors.initials: S
authors.lastname: Siwendu
authors.forename: Julie
authors.initials: J
authors.lastname: Jarand
authors.forename: Colin N
authors.initials: CN
authors.lastname: Menezes
authors.forename: Avril
authors.initials: A
authors.lastname: Burns
authors.forename: Thomas
authors.initials: T
authors.lastname: Victor
authors.forename: Robin
authors.initials: R
authors.lastname: Warren
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.forename: Martie
authors.initials: M
authors.lastname: van der Walt
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kvasnovsky
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054908:Extensively Drug-Resistant Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D013019:South Africa; D015996:Survival Rate; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents