Daria N Podlekareva1, Anne Marie W Efsen2, Anna Schultze3, Frank A Post4, Alena M Skrahina5, Alexander Panteleev6, Hansjakob Furrer7, Robert F Miller8, Marcelo H Losso9, Javier Toibaro9, Jose M Miro10, Anna Vassilenko11, Enrico Girardi12, Mathias Bruyand13, Niels Obel14, Jens D Lundgren2, Amanda Mocroft3, Ole Kirk2. 1. CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: daria.podlekareva@regionh.dk. 2. CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 3. Department of Infection and Population Health, University College London Medical School, London, UK. 4. Department of Sexual Health, King's College Hospital, London, UK. 5. Republican Research and Practical Centre for Pulmonology and TB, Minsk, Belarus. 6. Department of HIV/TB, TB Hospital 2, St Petersburg, Russia. 7. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland. 8. Centre for Sexual Health and HIV Research, University College London, London, UK. 9. Department of Immunocompromised, Hospital J M Ramos Mejia, Buenos Aires, Argentina. 10. Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain. 11. Belarusian State Medical University, Minsk, Belarus; Department of Infectious Diseases, City Clinical Hospital of infectious Diseases, Minsk, Belarus. 12. Department of Infectious Diseases INMI "L. Spallanzani", Ospedale L Spallanzani, Rome, Italy. 13. INSERM, ISPED, Centre Inserm U897-Epidemiologie-Biostatistique, Bordeaux, France. 14. Department of Infectious Diseases, Finsencentret, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: EU Seventh Framework Programme.
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. FINDINGS: 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). INTERPRETATION: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. FUNDING: EU Seventh Framework Programme.
Authors: A M W Efsen; A Schultze; R F Miller; A Panteleev; A Skrahin; D N Podlekareva; J M Miro; E Girardi; H Furrer; M H Losso; J Toibaro; J A Caylà; A Mocroft; J D Lundgren; F A Post; O Kirk Journal: J Infect Date: 2017-10-20 Impact factor: 6.072
Authors: Yanink Caro-Vega; Anna Schultze; Anne Marie W Efsen; Frank A Post; Alexander Panteleev; Aliaksandr Skrahin; Jose M Miro; Enrico Girardi; Daria N Podlekareva; Jens D Lundgren; Juan Sierra-Madero; Javier Toibaro; Jaime Andrade-Villanueva; Simona Tetradov; Jan Fehr; Joan Caylà; Marcelo H Losso; Robert F Miller; Amanda Mocroft; Ole Kirk; Brenda Crabtree-Ramírez Journal: BMC Infect Dis Date: 2018-04-23 Impact factor: 3.090
Authors: Francine Teixeira; Sonia M Raboni; Clea El Ribeiro; João Cb França; Anne C Broska; Nathalia Ls Souza Journal: Microbiol Insights Date: 2018-11-27