***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: RATIONALE Although interferon (IFN)-gamma release assays are approved for the diagnosis of latent tuberculosis infection ( LTBI ) , limited data exist regarding their performance in HIV infection . OBJECTIVES To compare tuberculin skin test ( TST ) results to the commercial IFN-gamma release assay QuantiFERON-TB Gold In-Tube ( QFT ) for the diagnosis of LTBI in HIV-infected adults . METHODS A total of 294 HIV-infected subjects sample d from two San Francisco cohorts underwent TST , using 5 TU of purified protein derivative , and QFT , measuring IFN-gamma response to Mycobacterium tuberculosis-specific RD-1 antigens . MAIN RESULTS Of 294 participants , 205 ( 70 % ) returned for an evaluable TST .  Concordance between QFT and TST was 89.3 % ( kappa=0.37 , p=0.007 ) . However , in subjects with positive test results by either TST or QFT , only 28 % ( 8/29 ) had positive test results by both modalities . TST-positive/QFT-negative discordant results were found in 5.1 % of subjects and TST-negative/QFT-positive discordance in 5.6 % . Indeterminate QFT results occurred in 5.1 % , all due to a failure to respond to the phytohemagglutinin-positive control . Subjects with a CD4(+ ) count of less than 100 cells/mm(3 ) had a relative risk of an indeterminate result of 4.24 ( 95 % confidence interval , 1.55 - 11.61 ; p=0.003 ) compared with those with a CD4(+ ) count of 100 or more . CONCLUSIONS Overall concordance between QFT and TST in HIV infection was high , but agreement among subjects with positive tests by either modality was low We evaluated the performance of T-SPOT.TB ( a commercial interferon gamma release assay ) and its accuracy for the diagnosis of active tuberculosis ( TB ) among HIV-infected subjects with advanced immunodeficiency . In a clinical prospect i ve study , we assessed the performance of T-SPOT.TB for the diagnosis of active TB in HIV-infected patients with CD4 cell counts below 350 cells/mm(3 ) who were naive to antiretroviral and anti-TB therapies . Results were available from 147 patients , of whom 38 ( 25.9 % ) had active TB . The majority ( 85 % ) of the participants were male , with a median age of 40 years and a median CD4 cell count of 77 cells/mm(3 ) .  T-SPOT.TB yielded 15 ( 10.2 % ) indeterminate results . The indeterminate results were not associated with CD4 cell counts . However , younger patients were more likely to have an indeterminate result ( OR = 0.91 per unit increase in age , p = 0.007 ) . After excluding the indeterminate results , the sensitivity of T-SPOT.TB for the diagnosis of active TB was 37.1 % and the specificity was 88.7 % . The sensitivity of the T-SPOT.TB was independent of the CD4 cell count . However , its specificity was higher when used for patients with CD4 cell counts < 100 cells/mm(3 ) when compared to patients with CD4 cell counts ≥100 cells/mm(3 ) ( 97.9 % vs. 79.6 % , p = 0.008 ) . T-SPOT.TB could not be used as a routine tool to screen for active TB  among HIV-infected patients with advanced immunodeficiency because of its poor performance and low sensitivity . However , it may be used as an adjunctive tool to diagnose active TB in this population due to its high specificity Objective : To evaluate the interferon-γ-releasing assays QuantiFERON-tuberculosis ( TB ) Gold and T-SPOT.TB in addition to tuberculin skin test ( TST ) for diagnosis of latent tuberculosis infection in HIV patients . Design , setting and participants : Prospect i ve cross-sectional study for asymptomatic HIV-infected out patients from a large University hospital . Intervention : Simultaneous performance of QuantiFERON-TB Gold , T-SPOT.TB and TST . Main outcome measures : Incidence and risk factors for a positive test reaction and the concordance ( κ ) between the tests were investigated . Results : Of 286 enrolled patients , 81 % were men ; median age was 44 years , the median CD4 cell count 408/μl ( range 7–1510 ) with a median nadir of 126/μl ( range 0–749 ) . A number of patients ( 63.8 % ) had undetectable HIV RNA ( < 50 copies/ml ) . Both T-SPOT.TB and QuantiFERON-TB showed more positive test results than TST : 25.2 and 20.0 % ( P = 0.133 ) compared with 12.8 % ( P < 0.001 and P = 0.008 , respectively ) . Agreement between T-SPOT.TB and TST ( κ = 0.201 ) respectively QuantiFERON-TB and TST ( κ = 0.335 ) was fair , but only poor between the serological assays ( κ = 0.146 ) . T-SPOT.TB provided more indeterminate results than QuantiFERON-TB ( 8 vs. 1/256 , P < 0.01 ) . Patients with a positive QuantiFERON-TB result had higher median CD4 cell counts ( 457 vs. 405 cells/μl for patients with negative result , P = 0.044 ) ; the amount of released interferon-γ correlated with CD4 cell counts ( ρ = 0.199 ; P < 0.002 ) . T-SPOT.TB results were independent from CD4 cell counts . Conclusion : In HIV-infected patients from a low prevalence TB country , both interferon-γ assays are more sensitive than TST , but seem to be less sensitive than in immunocompetent patients . The blood tests show poor agreement and differ in their dependence on the CD4 cell count BACKGROUND Immunocompromised persons infected with Mycobacterium tuberculosis ( MTB ) have increased risk of tuberculosis ( TB ) reactivation , but their management is hampered by the occurrence of false-negative results of the tuberculin skin test ( TST ) . The T-cell interferon (IFN)-gamma release blood assays T-SPOT.TB ( TS.TB ) [ Oxford Immunotec ; Abingdon , UK ] and QuantiFERON-TB Gold In-Tube ( QFT-IT ) [ Cellestis Ltd ; Carnegie , VIC , Australia ] might improve diagnostic accuracy for latent TB infection ( LTBI ) in high-risk persons , although their performance in different groups of immunocompromised patients is largely unknown . METHODS AND RESULTS Over a 1-year period , we prospect ively enrolled patients in three different immunosuppressed groups , as follows : 120 liver transplantation c and i date s ( LTCs ) ; 116 chronically HIV-infected persons ; and 95 patients with hematologic malignancies ( HMs ) .  TST , TS.TB , and QFT-IT were simultaneously performed , their results were compared , and intertest agreement was evaluated . Overall , TST provided fewer positive results ( 10.9 % ) than TS.TB ( 18.4 % ; p < 0.001 ) and QFT-IT ( 15.1 % ; p = 0.033 ) . Significantly fewer  HIV-infected individuals had at least one positive test ( 9.5 % ) compared with LTCs ( 35.8 % ; p < 0.001 ) and patients with HMs ( 29.5 % ; p < 0.001 ) . Diagnostic agreement between tests was moderate ( kappa = 0.40 to 0.65 ) and decreased in the HIV-infected group when the results of the TS.TB were compared with either TST ( kappa = 0.16 ) or QFT-IT ( kappa = 0.19 ) . Indeterminate blood test results due to low positive control values were significantly more frequent with QFT-IT ( 7.2 % ) than with TS.TB ( 0.6 % ; p < 0.001 ) . CONCLUSIONS Blood tests identified significantly more patients as being infected with MTB than TST , although diagnostic agreement varied across groups . Based on these results , we recommend tailoring application of the new blood IFN-gamma assays for LTBI in different high-risk groups and advise caution in their current use in immunosuppressed patients RATIONALE Two forms of the  IFN-gamma release assay  ( IFNGRA ) to detect tuberculosis infection are available , but neither has been evaluated in comparable HIV-infected and uninfected persons in a high tuberculosis incidence environment . OBJECTIVE To compare the ability of the T-SPOT.TB ( Oxford Immunotec , Abingdon , UK ) , QuantiFERON-TB Gold ( Cellestis , Melbourne , Australia ) , and Mantoux tests to identify latent tuberculosis in HIV-infected and uninfected persons . METHODS A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counseling and testing center for HIV infection in Khayelitsha , a deprived urban South African community with an HIV antenatal seroprevalence of 33 % and a tuberculosis incidence of 1,612 per 100,000 . MEASUREMENTS AND MAIN RESULTS One hundred and sixty ( 74 HIV(+ ) and 86 HIV(- ) ) persons were enrolled . A lower proportion of Mantoux results was positive in HIV-infected subjects compared with HIV-uninfected subjects ( p < 0.01 ) . By contrast , the proportion of positive IFNGRAs was not significantly different in HIV-infected persons for the T-SPOT.TB test ( 52 vs. 59 % ; p = 0.41 ) or the QuantiFERON-TB Gold test ( 43 and 46 % ; p = 0.89 ) . Fair agreement between the Mantoux test ( 5- and 10-mm cutoffs ) and the IFNGRA was seen in HIV-infected people ( kappa = 0.52 - 0.6 ) . By contrast , poor agreement between the Mantoux and QuantiFERON-TB Gold tests was observed in the HIV-uninfected group ( kappa = 0.07 - 0.30 , depending on the Mantoux cutoff ) . The pattern was similar for T-SPOT.TB ( kappa = 0.18 - 0.24 ) . INTERPRETATION IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection . However , agreement between the tests and with the Mantoux test varied from poor to fair . This highlights the need for prospect i ve studies to determine which test may predict the subsequent risk of tuberculosis There are limited data on the efficacy of T cell‐based assays to detect tuberculosis ( TB ) antigen‐specific responses in immune‐deficient human immunodeficiency virus ( HIV ) patients . The aim of this study is to determine whether TB antigen‐specific immune responses can be detected in patients with HIV‐1 infection , especially in those with advanced disease ( CD4 T cell count < 300 cells/µl ) . An enzyme‐linked immunospot ( ELISPOT ) assay , which detects interferon (IFN)‐γ secreted by T cells exposed to TB antigens , was used to assess specific immune responses in a prospect i ve study of 201 HIV‐1‐infected patients with risk factors for TB infection , attending a single HIV unit . The performance of the ELISPOT assay to detect TB antigen‐specific immune responses is independent of CD4 T cell counts in HIV‐1 patients . The sensitivity and specificity of this assay for the diagnosis of active tuberculosis does not differ significantly from values obtained in immunocompetent subjects . The negative predictive value of the TB ELISPOT test is 98·2 % . A positive predictive value of 86 % for the diagnosis of active tuberculosis was found when the combined number of early secretory antigen target‐6 ( ESAT‐6 ) and culture filtrate protein‐10 ( CFP‐10 ) IFN‐γ spots to CD4 T cell count ratio was > 1·5 . TB antigen‐specific immune responses can be detected in HIV patients with low CD4 T cell counts using ELISPOT technology in a routine diagnostic laboratory and is a useful test to exclude TB infection in immune‐deficient HIV‐1 patients . A combination of TB antigen‐specific IFN‐γ responses and CD4 T cell counts has the potential to distinguish active tuberculosis from latent infection BACKGROUND The sensitivity of whole-blood interferon-gamma release assays to detect or predict active tuberculosis in individuals infected with human immunodeficiency virus type 1 ( HIV-1 ) has as yet not been determined . Methods . In this prospect i ve , longitudinal , single-center study , 830 HIV-1-infected patients underwent testing with the QuantiFERON-TB Gold In-Tube ( QFT-GIT ) assay . Clinical screening for active tuberculosis was performed at least every 3 months for a median follow-up time of 19 months . RESULTS At baseline , the QFT-GIT assay yielded positive or indeterminate results in 44 ( 5.3 % ) and 47 ( 5.7 % 
    Output:
    
/ SIGNIFICANCE IGRAs have suboptimal accuracy for confirming or ruling out active tuberculosis disease in HIV-infected adults .
While their predictive value for incident active tuberculosis is modest , a negative QFT-GIT implies a very low short- to medium-term risk .