Int J Tuberc Lung Dis. 2014 Feb;18(2):180-7. doi: 10.5588/ijtld.13.0276.

Low prevalence of positive interferon-gamma tests in HIV-positive long-term immigrants in Norway.

Pullar ND1, Steinum H2, Tonby K3, Heggelund L4, Leiva RA5, Ofstad R6, Bruun JN1, Dyrhol-Riise AM7.

  • 1Department of Internal Medicine, Section for Infectious Diseases, University Hospital of Northern Norway, Tromsø, Norway;      Department of Clinical Medicine, Faculty of Health Sciences, University of  Tromsø, Tromsø, Norway.
  • 2Department of Infectious Diseases, Trondheim University Hospital, Trondheim, Norway.
  • 3Department of Infectious Diseases, Oslo University Hospital (Ullevål), Nydalen, Oslo, Norway; Institute of Clinical Medicine,      Faculty of Medicine, University of Oslo, Oslo, Norway.
  • 4Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Section for Clinical Immunology and      Infectious Diseases, Oslo University Hospital (Rikshospitalet), Nydalen, Oslo, Norway; Department of Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway.
  • 5Department of Medicine, Haukeland University Hospital, Bergen, Norway.
  • 6Department of Internal Medicine, Haugesund Hospital, Haugesund, Norway.
  • 7Department of Infectious Diseases, Oslo University Hospital (Ullevål), Nydalen, Oslo, Norway; Institute of Clinical Medicine,      Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway; and Department of Clinical Science, University of Bergen, Bergen, Norway.

 

Abstract

OBJECTIVE: To determine the prevalence and predictors of positive interferon-gamma release assays (IGRAs) and tuberculin skin tests (TSTs) in human immunodeficiency virus (HIV) infected patients in Norway, a low tuberculosis (TB) endemic country.

DESIGN: Multicentre cross-sectional study of 298 HIV patients tested with QuantiFERON®-TB Gold In-Tube (QFT-GIT), T-SPOT®.TB (T-SPOT) and TST.

RESULTS: A total of 77/298 (26%) QFT-GIT, 29/117 (25%) T-SPOT and 52/217 (24%) TSTs (≥ 5 mm) were positive. The median CD4 count was 427 cells/l. Three QFT-GIT results but no T-SPOT results were indeterminate. Of 52 TST-positive patients, 34 (65%) were QFT-GIT-positive (median interferon-gamma [IFN-] 4.38 international units [IU]/ml), compared to 16% of the TST-negative patients (median INF- 0.81 IU/ml, P < 0.001). Origin from a TB-endemic country, previous active TB and TB exposure were associated with a positive QFT-GIT (P 0.01). Patients from TB-endemic countries living in Norway for ≥ 10 years had lower odds of a positive QFT-GIT (12%; OR 0.17, 95%CI 0.060.53, P 0.002) than patients with 03 years’ residence (49%).

CONCLUSION: The prevalence of positive IGRAs in HIV-infected patients was high in this low TB endemic setting. Lower QFT-GIT positivity in long-term residents from TB-endemic countries may reflect a waning of TB-specific immune responses.

PMID: 24429310

 

SUPPLEMENT

This is the first study, to our knowledge, reporting a lower prevalence of positive interferon-gamma release assays in HIV patients from tuberculosis (TB) high-endemic countries who had lived for ≥10 years in a TB low-endemic country compared to those with shorter stay. This finding could indicate a waning of M. tuberculosis-specific immune responses in HIV positive immigrants after prolonged stay in a TB low-endemic setting and may have relevant policy implications for TB-prophylactic treatment in TB low-endemic countries.

This study is also the first of its kind in Norway, a TB low-endemic country. The last few years, Norway has had an increase in active TB incidence due to immigration from TB high-endemic countries, which accounts for 80-90% of new TB cases and 70% of new HIV cases. There is however no surveillance data of HIV/TB co-infections in Norway.

Our manuscript presents cross-sectional data from a cohort of HIV-positive patients recruited from 7 out-patient clinics in Norway in whom IGRA and tuberculin skin test (TST) were performed. IGRAs performed were QuantiFERON-TB Gold In-Tube® assay (QFT) and TB-SPOT.TB®) (TSPOT). Our goal was to determine the prevalence of positive IGRA, evaluate discordant IGRA and TST, and study risk factors associated with positive tests in a TB low-endemic setting.

 

Important findings in our study:

1)      We found a higher prevalence of positive IGRA than earlier reported from Scandinavian countries. The prevalence of positive IGRA was 25% (TSPOT) and 26% (QFT) for the entire HIV positive cohort, whereas the prevalence of positive IGRA in HIV positive patients from TB high-endemic countries was 35% (TSPOT) and 33% (QFT).

2)      We found a lower prevalence of positive IGRA in HIV patients from TB high-endemic countries who had lived ≥10 years in Norway compared to those living 0-3 years (12% vs. 49%). The odds ratios for a positive QFT was significantly lower in the latter group also after adjusting for CD4 count at enrolment and antiretroviral therapy. This decline could not be explained by previous latent TB treatment and could indicate waning of TB specific immune responses over time in settings of low infectious pressure. However, longitudinal studies of longer duration are necessary to further examine the dynamics of TB-specific immune responses and prognosis in HIV-patients living in TB low burden areas.

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