title: CD4 cell levels during treatment for tuberculosis (TB) in Ethiopian adults and clinical markers associated with CD4 lymphocytopenia.
abstract: BACKGROUND
  The clinical correlations and significance of subnormal CD4 levels in HIV-negative patients with TB are unclear. We have determined CD4 cell levels longitudinally during anti-tuberculosis treatment (ATT) in patients, with and without HIV co-infection, and their associations with clinical variables.
  
  
  METHODS
  Adults diagnosed with TB (maximum duration of ATT for 2 weeks, and with no history of antiretroviral therapy (ART) in HIV-positive subjects) were included consecutively in eight out-patient clinics in Ethiopia. Healthy individuals were recruited for comparison at one of the study health centers. Data on patient characteristics and physical findings were collected by trained nurses following a structured questionnaire at inclusion and on follow-up visits at 2 and 6 months. In parallel, peripheral blood CD4 cell levels were determined. The evolution of CD4 cell levels during ATT was assessed, and the association between clinical characteristics and low CD4 cell levels at baseline was investigated using regression analysis.
  
  
  RESULTS
  In total, 1116 TB patients were included (307 HIV-infected). Among 809 HIV-negative patients, 200 (25%) had subnormal CD4 cell counts (<500 cells/mm(3)), with <350 cells/mm(3) in 82 (10%) individuals. CD4 cell levels increased significantly during the course of ATT in both HIV+ and HIV- TB-patients, but did not reach the levels in healthy subjects (median 896 cells/mm(3)). Sputum smear status, signs of wasting (low mid upper arm circumference (MUAC)), and bedridden state were significantly associated with low CD4 cell counts.
  
  
  CONCLUSIONS
  A high proportion of Ethiopian TB patients have subnormal CD4 cell counts before starting treatment. Low CD4 cell levels are associated with smear positive disease and signs of wasting. The continuous increase of CD4 cell counts during the course of ATT suggest a reversible impact of active TB on CD4 cell homeostasis, which may be considered in interpretation of CD4 cell counts in HIV/TB co-infected subjects.
authors.affiliation: Infectious Diseases Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Malmö, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Skogmar
authors.affiliation: Department of Medical Microbiology, Faculty of Health Sciences, Linköping University, Linköping, Sweden ; Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schön
authors.affiliation: Infectious Diseases Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Malmö, Sweden ; Ministry of Health, Addis Ababa, Ethiopia.
authors.forename: Taye Tolera
authors.initials: TT
authors.lastname: Balcha
authors.affiliation: Oromia Regional Health Bureau, Addis Ababa, Ethiopia.
authors.forename: Zelalem Habtamu
authors.initials: ZH
authors.lastname: Jemal
authors.affiliation: Columbia University Mailman School of Public Health, International Center for AIDS Care and Treatment Programs- Ethiopia, Addis Ababa, Ethiopia.
authors.forename: Gudeta
authors.initials: G
authors.lastname: Tibesso
authors.affiliation: Research and Development Unit, Skåne University Hospital, Lund, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Björk
authors.affiliation: Infectious Diseases Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Malmö, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Björkman
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D015331:Cohort Studies; D060085:Coinfection; D005002:Ethiopia; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D008231:Lymphopenia / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers