title: The predictive value of current haemoglobin levels for incident tuberculosis and/or mortality during long-term antiretroviral therapy in South Africa: a cohort study.
abstract: BACKGROUND
  Low haemoglobin concentrations may be predictive of incident tuberculosis (TB) and death in HIV-infected patients receiving antiretroviral therapy (ART), but data are limited and inconsistent. We examined these relationships retrospectively in a long-term South African ART cohort with multiple time-updated haemoglobin measurements.
  
  
  METHODS
  Prospectively collected clinical data on patients receiving ART for up to 8 years in a community-based cohort were analysed. Time-updated haemoglobin concentrations, CD4 counts and HIV viral loads were recorded, and TB diagnoses and deaths from all causes were ascertained. Anaemia severity was classified using World Health Organization criteria. TB incidence and mortality rates were calculated and Poisson regression models were used to identify independent predictors of incident TB and mortality, respectively.
  
  
  RESULTS
  During a median follow-up of 5.0 years (IQR, 2.5-5.8) of 1,521 patients, 476 cases of incident TB and 192 deaths occurred during 6,459 person-years (PYs) of follow-up. TB incidence rates were strongly associated with time-updated anaemia severity; those without anaemia had a rate of 4.4 (95%CI, 3.8-5.1) cases/100 PYs compared to 10.0 (95%CI, 8.3-12.1), 26.6 (95%CI, 22.5-31.7) and 87.8 (95%CI, 57.0-138.2) cases/100 PYs in those with mild, moderate and severe anaemia, respectively. Similarly, mortality rates in those with no anaemia or mild, moderate and severe time-updated anaemia were 1.1 (95%CI, 0.8-1.5), 3.5 (95%CI, 2.7-4.8), 11.8 (95%CI, 9.5-14.8) and 28.2 (95%CI, 16.5-51.5) cases/100 PYs, respectively. Moderate and severe anaemia (time-updated) during ART were the strongest independent predictors for incident TB (adjusted IRR = 3.8 [95%CI, 3.0-4.8] and 8.2 [95%CI, 5.3-12.7], respectively) and for mortality (adjusted IRR = 6.0 [95%CI, 3.9-9.2] and adjusted IRR = 8.0 [95%CI, 3.9-16.4], respectively).
  
  
  CONCLUSIONS
  Increasing severity of anaemia was associated with exceptionally high rates of both incident TB and mortality during long-term ART. Patients receiving ART who have moderate or severe anaemia should be prioritized for TB screening using microbiological assays and may require adjunctive clinical interventions.
authors.affiliation: George Washington University School of Medicine and Health Sciences, 2300 Eye St, NW, Washington, DC, 20037, USA. andrewkerkhoff@gmail.com.|Department of Global Health, Academic Medical Center, Amsterdam Institute for Global Health and Development, University of Amsterdam, Amsterdam, the Netherlands. andrewkerkhoff@gmail.com.|The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. andrewkerkhoff@gmail.com.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kerkhoff
authors.affiliation: The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Robin.Wood@hiv-research.org.za.|Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. Robin.Wood@hiv-research.org.za.
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.affiliation: Department of Global Health, Academic Medical Center, Amsterdam Institute for Global Health and Development, University of Amsterdam, Amsterdam, the Netherlands. frank.cobelens@kncvtbc.org.|KNCV Tuberculosis Foundation, The Hague, the Netherlands. frank.cobelens@kncvtbc.org.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Cobelens
authors.affiliation: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. ankurgupta@doctors.org.uk.
authors.forename: Ankur
authors.initials: A
authors.lastname: Gupta-Wright
authors.affiliation: The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Linda-Gail.Bekker@hiv-research.org.za.
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.affiliation: The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Stephen.Lawn@lshtm.ac.uk.|Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. Stephen.Lawn@lshtm.ac.uk.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
mesh_terms: D000328:Adult; D000740:Anemia / Q000097:blood / Q000175:diagnosis; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D015994:Incidence; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D012189:Retrospective Studies; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000097:blood* / Q000453:epidemiology*
chemical_list: D006454:Hemoglobins