title: Treatment of drug-resistant tuberculosis with bedaquiline in a high HIV prevalence setting: an interim cohort analysis.
abstract: BACKGROUND
  South Africa has a large burden of extensively drug-resistant tuberculosis (XDR-TB); only 15% of XDR-TB patients have successful outcomes.
  
  
  OBJECTIVE
  To describe the safety and effectiveness of bedaquiline (BDQ) in the South African BDQ Clinical Access Programme.
  
  
  METHODS
  An interim cohort analysis.
  
  
  RESULTS
  Of the first 91 patients enrolled between March 2013 and July 2014 (with follow-up until August 2014), 54 (59%) were human immunodeficiency virus (HIV) infected. The median CD4 count was 239 cells/μl, and all patients were on antiretroviral therapy (ART) at initiation of BDQ; 33 had XDR-TB, 41 were pre-XDR-TB with fluoroquinolone resistance and 17 were pre-XDR-TB with resistance to an injectable. Of the 91 patients, 58 (64%) had completed 24 weeks of BDQ, 28 were still on BDQ, 3 were lost to follow-up, 1 had died and 1 had BDQ withdrawn following atrial fibrillation. Of the 63 patients with 6 months follow-up, 48 (76%) had either culture-converted or remained culture-negative after initiation of BDQ. QTcF was monitored monthly and exceeded 500 ms in three participants; this resolved in all three.
  
  
  CONCLUSIONS
  Interim safety and culture conversion outcomes for patients accessing BDQ in South Africa, including HIV-infected patients on ART and patients with pre-XDR- and XDR-TB, suggest that BDQ may be both efficacious and safe.
authors.affiliation: National Department of Health, Pretoria, South Africa.
authors.forename: N
authors.initials: N
authors.lastname: Ndjeka
authors.affiliation: Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Right to Care, Johannesburg, South Africa.
authors.forename: F
authors.initials: F
authors.lastname: Conradie
authors.affiliation: Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Right to Care, Johannesburg, South Africa.
authors.forename: K
authors.initials: K
authors.lastname: Schnippel
authors.affiliation: Médecins sans Frontières, Khayelitsha, Cape Town, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: Hughes
authors.affiliation: TB/HIV Investigative Network of Kwazulu-Natal, Durban, South Africa.
authors.forename: N
authors.initials: N
authors.lastname: Bantubani
authors.affiliation: Klerksdorp Tshepong Hospital Complex, Klerksdorp, South Africa.
authors.forename: H
authors.initials: H
authors.lastname: Ferreira
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: G
authors.initials: G
authors.lastname: Maartens
authors.affiliation: National Department of Health, Pretoria, South Africa.
authors.forename: D
authors.initials: D
authors.lastname: Mametja
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: G
authors.initials: G
authors.lastname: Meintjes
authors.affiliation: Sizwe Tropical Disease Hospital, Johannesburg, South Africa.
authors.forename: X
authors.initials: X
authors.lastname: Padanilam
authors.affiliation: Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Klerksdorp Tshepong Hospital Complex, Klerksdorp, South Africa.
authors.forename: E
authors.initials: E
authors.lastname: Variava
authors.affiliation: Kwazulu-Natal Research Institute for TB and HIV, Durban, South Africa.
authors.forename: A
authors.initials: A
authors.lastname: Pym
authors.affiliation: National Department of Health, Pretoria, South Africa.
authors.forename: Y
authors.initials: Y
authors.lastname: Pillay
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D064687:Diarylquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D064687:Diarylquinolines; D024841:Fluoroquinolones; C493870:bedaquiline