title: Does antiretroviral therapy reduce HIV-associated tuberculosis incidence to background rates? A national observational cohort study from England, Wales, and Northern Ireland.
abstract: BACKGROUND
  Whether the incidence of tuberculosis in HIV-positive people receiving long-term antiretroviral therapy (ART) remains above background population rates is unclear. We compared tuberculosis incidence in people receiving ART with background rates in England, Wales, and Northern Ireland.
  
  
  METHODS
  We analysed a national cohort of HIV-positive individuals linked to the national tuberculosis register. Tuberculosis incidence in the HIV-positive cohort (2007-11) was stratified by ethnic origin and time on ART and compared with background rates (2009). Ethnic groups were defined as follows: the black African group included all individuals of black African origin, including those born in the UK and overseas; the white ethnic group included all white individuals born in the UK and overseas; the south Asian group included those of Indian, Pakistani, and Bangladeshi origin, born in the UK and overseas; and the other ethnic group included all other ethnic origins, including black Afro-Caribbeans.
  
  
  RESULTS
  The HIV-positive cohort comprised 79 919 individuals, in whom there were 1550 incident cases in 231 664 person-years of observation (incidence 6·7 cases per 1000 person-years). Incidence of tuberculosis in the HIV-positive cohort was 13·6 per 1000 person-years in black Africans and 1·7 per 1000 person-years in white individuals. Incidence of tuberculosis during long-term ART (≥5 years) in black Africans with HIV was 2·4 per 1000 person-years, similar to background rates of 1·9 per 1000 person-years in this group (rate ratio 1·2, 95% CI 0·96-1·6; p=0·083); but in white individuals with HIV on long-term ART the incidence of 0·5 per 1000 person-years was higher than the background rate of 0·04 per 1000 person-years (rate ratio 14·5, 9·4-21·3; p<0·0001). The increased incidence relative to background in white HIV-positive individuals persisted when analysis was restricted to person-time accrued on ART with CD4 counts of at least 500 cells per μL and when white HIV-positive individuals born abroad were excluded.
  
  
  CONCLUSIONS
  Tuberculosis incidence is unacceptably high irrespective of HIV status in black Africans. In white individuals with HIV, tuberculosis incidence is significantly higher than background rates in white people despite long-term ART. Expanded testing and treatment for latent tuberculosis infection to all HIV-infected adults, irrespective of ART status and CD4 cell count, might be warranted.
  
  
  BACKGROUND
  Public Health England.
authors.affiliation: Division of Medicine, University College London, London, UK; HIV/STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK. Electronic address: rishi.gupta@doctors.org.uk.
authors.forename: Rishi K
authors.initials: RK
authors.lastname: Gupta
authors.affiliation: HIV/STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Rice
authors.affiliation: HIV/STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Brown
authors.affiliation: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
authors.forename: H Lucy
authors.initials: HL
authors.lastname: Thomas
authors.affiliation: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK; Centre for Infectious Disease Epidemiology, University College London, London, UK.
authors.forename: Dominik
authors.initials: D
authors.lastname: Zenner
authors.affiliation: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Anderson
authors.affiliation: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Debora
authors.initials: D
authors.lastname: Pedrazzoli
authors.affiliation: Chelsea & Westminster Hospitals NHS Foundation Trust, London, UK.
authors.forename: Anton
authors.initials: A
authors.lastname: Pozniak
authors.affiliation: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK; MRC Clinical Trials Unit and Centre for Infectious Disease Epidemiology, University College London, London, UK.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Abubakar
authors.affiliation: HIV/STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Delpech
authors.affiliation: Division of Medicine, University College London, London, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Lipman
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004739:England / Q000453:epidemiology / Q000208:ethnology; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland / Q000453:epidemiology / Q000208:ethnology; D014376:Tuberculosis / Q000453:epidemiology* / Q000208:ethnology / Q000209:etiology; D014852:Wales / Q000453:epidemiology / Q000208:ethnology
chemical_list: D019380:Anti-HIV Agents