title: Clofazimine in the treatment of extensively drug-resistant tuberculosis with HIV coinfection in South Africa: a retrospective cohort study.
abstract: BACKGROUND
  Extensively drug-resistant (XDR) tuberculosis (TB) and HIV coinfection is associated with low cure rates and high mortality. Clofazimine has shown activity in vitro against Mycobacterium tuberculosis, but clinical experience with clofazimine in XDR-TB and HIV coinfection is limited.
  
  
  METHODS
  This was a retrospective cohort study of adult XDR-TB patients in KwaZulu-Natal, South Africa, treated with either a clofazimine- or non-clofazimine-containing XDR-TB treatment regimen. The primary outcome measure was TB culture conversion at 6 months. Survival analysis and multivariate logistic regression compared time to event in different strata and identified risk factors for TB culture conversion.
  
  
  RESULTS
  Between August 2009 and July 2011, eligible XDR-TB patients (n = 85) were initiated on treatment for XDR-TB. Most patients (86%) were HIV-infected and receiving antiretroviral therapy (90%). Patients receiving a clofazimine-containing regimen (n = 50) had a higher percentage of culture conversion (40%) compared with patients (n = 35) receiving a non-clofazimine regimen (28.6%). On multivariate analysis, there was a 2-fold increase in TB culture conversion at 6 months (hazard rate ratio 2.54, 95% CI 0.99-6.52, P = 0.05) in the group receiving a clofazimine-containing regimen. Adverse effects due to clofazimine were minor and rarely life-threatening.
  
  
  CONCLUSIONS
  Clofazimine was associated with improved culture conversion in the treatment of XDR-TB/HIV. Adverse effects were minor and non-life-threatening. Based on these preliminary data, further study of clofazimine in XDR-TB/HIV treatment is warranted. Given the present low rates of culture conversion in XDR-TB treatment, we recommend empirical inclusion of clofazimine in treatment regimens for XDR-TB.
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, 4013, South Africa padayatchin@ukzn.ac.za.
authors.forename: N
authors.initials: N
authors.lastname: Padayatchi
authors.affiliation: Gulf Coast Pulmonary Medicine, Port Charlotte, FL 33952, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gopal
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, 4013, South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Naidoo
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, 4013, South Africa.
authors.forename: L
authors.initials: L
authors.lastname: Werner
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, 4013, South Africa.
authors.forename: K
authors.initials: K
authors.lastname: Naidoo
authors.affiliation: King Dinuzulu Hospital, PO Box Dormerton 4015, South Africa.
authors.forename: I
authors.initials: I
authors.lastname: Master
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, 4013, South Africa Division of Pulmonary Medicine, Department of Internal Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: O'Donnell
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D002991:Clofazimine / Q000627:therapeutic use*; D015331:Cohort Studies; D060085:Coinfection; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000995:Antitubercular Agents; D002991:Clofazimine
keywords: XDR-TB; culture conversion; repurposed drugs