title: Incomplete restoration of Mycobacterium tuberculosis-specific-CD4 T cell responses despite antiretroviral therapy.
abstract: OBJECTIVE
  Despite antiretroviral therapy (ART), HIV-infected persons have increased risk of active tuberculosis (TB). PPD and combined ESAT-6 and CFP-10-specific-CD4 (EC-Sp-CD4) responses were examined over 96 weeks.
  
  
  METHODS
  HIV-infected, ART-naive Thai adults with CD4 T cell count ≤350 cells/μL starting ART were assessed at baseline, wk4, 8, 12, 24, 48 and 96. PPD and EC-Sp-CD4 T cells were detected by CD25/CD134 co-expression after stimulation with antigens.
  
  
  RESULTS
  Fifty subjects were enrolled, 39 were male, median age 32 yrs, median baseline CD4 T cell count 186 cells/μL and plasma HIV-viral-load 4.9log10 copies/mL. Seventeen were TB-sensitised. At baseline, 25 had positive PPD and 15 had positive EC-Sp-CD4 response. CD4 T cell count <100 cells/μL was less (P = 0.005) and TB-sensitisation was more likely (P = 0.013) to be associated with positive baseline PPD-Sp-CD4 response. At wk4, the number of subjects with positive PPD-Sp-CD4 response rose to 35 (P = 0.021). Mean PPD-Sp-CD4 T cells increased at wk4 (P = 0.017) in patients not classified as TB-sensitised. The number of subjects with positive EC-Sp-CD4 response did not change significantly post ART. In TB-sensitised patients, mean EC-Sp-CD4 T cells declined to below baseline from wk12 (P = 0.010) onwards. EC-Sp-CD4 responses were undetectable in 3 out of 17 TB-sensitised patients.
  
  
  CONCLUSIONS
  Restoration of responses to TB-antigens was incomplete and inconsistent under the employed experimental conditions and may account for persistent increased risk of TB despite ART.
authors: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia; HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Electronic address: d.hsu@amr.org.au.
authors: Denise C
authors: DC
authors: Hsu
authors: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia; HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors: Stephen J
authors: SJ
authors: Kerr
authors: HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors: Parawee
authors: P
authors: Thongpaeng
authors: HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors: Thatri
authors: T
authors: Iampornsin
authors: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia; St Vincent's Centre for Applied Medical Research, Sydney, Australia; UCL Research Department of Infection and Population Health, UCL, London, United Kingdom.
authors: Sarah L
authors: SL
authors: Pett
authors: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia; St Vincent's Centre for Applied Medical Research, Sydney, Australia.
authors: John J
authors: JJ
authors: Zaunders
authors: HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors: Anchalee
authors: A
authors: Avihingsanon
authors: HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors: Sasiwimol
authors: S
authors: Ubolyam
authors: HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors: Jintanat
authors: J
authors: Ananworanich
authors: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia; St Vincent's Centre for Applied Medical Research, Sydney, Australia.
authors: Anthony D
authors: AD
authors: Kelleher
authors: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia; St Vincent's Centre for Applied Medical Research, Sydney, Australia.
authors: David A
authors: DA
authors: Cooper
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001426:Bacterial Proteins / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013785:Thailand; D014373:Tuberculin / Q000276:immunology; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D014373:Tuberculin
keywords: Antiretroviral therapy; HIV infection; Immune restoration; MTB-specific-CD4 T cells; Tuberculosis