title: Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study.
abstract: BACKGROUND
  Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study.
  
  
  METHODS
  Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models.
  
  
  RESULTS
  Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p<0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p<0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p<0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p<0·0001).
  
  
  CONCLUSIONS
  Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe.
  
  
  BACKGROUND
  EU Seventh Framework Programme.
authors.affiliation: CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: daria.podlekareva@regionh.dk.
authors.forename: Daria N
authors.initials: DN
authors.lastname: Podlekareva
authors.affiliation: CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne Marie W
authors.initials: AM
authors.lastname: Efsen
authors.affiliation: Department of Infection and Population Health, University College London Medical School, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Schultze
authors.affiliation: Department of Sexual Health, King's College Hospital, London, UK.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Post
authors.affiliation: Republican Research and Practical Centre for Pulmonology and TB, Minsk, Belarus.
authors.forename: Alena M
authors.initials: AM
authors.lastname: Skrahina
authors.affiliation: Department of HIV/TB, TB Hospital 2, St Petersburg, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Panteleev
authors.affiliation: Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.affiliation: Centre for Sexual Health and HIV Research, University College London, London, UK.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Miller
authors.affiliation: Department of Immunocompromised, Hospital J M Ramos Mejia, Buenos Aires, Argentina.
authors.forename: Marcelo H
authors.initials: MH
authors.lastname: Losso
authors.affiliation: Department of Immunocompromised, Hospital J M Ramos Mejia, Buenos Aires, Argentina.
authors.forename: Javier
authors.initials: J
authors.lastname: Toibaro
authors.affiliation: Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miro
authors.affiliation: Belarusian State Medical University, Minsk, Belarus; Department of Infectious Diseases, City Clinical Hospital of infectious Diseases, Minsk, Belarus.
authors.forename: Anna
authors.initials: A
authors.lastname: Vassilenko
authors.affiliation: Department of Infectious Diseases INMI "L. Spallanzani", Ospedale L Spallanzani, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.affiliation: INSERM, ISPED, Centre Inserm U897-Epidemiologie-Biostatistique, Bordeaux, France.
authors.forename: Mathias
authors.initials: M
authors.lastname: Bruyand
authors.affiliation: Department of Infectious Diseases, Finsencentret, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.affiliation: CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.affiliation: Department of Infection and Population Health, University College London Medical School, London, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.affiliation: CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use; D015331:Cohort Studies; D058872:Epidemics; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007843:Latin America / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality*; D018088:Tuberculosis, Multidrug-Resistant / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents