The diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis is associated with CD4+ T-cell counts

The diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis is associated with CD4+ T-cell counts | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article The diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis is associated with CD4+ T-cell counts Mengyan Wang, Tongtong Chen, Xiaotian Dong, Zhongdong Zhang, Jinchuan Shi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.16261/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: To investigate the factors associated with the diagnostic performance of interferon-gamma release assay (IGRA) in HIV infected patients with active tuberculosis (TB). Methods: We retrospectively analyzed the data of HIV infected patients with active tuberculosis patients from 2016-2019 who conformed with the inclusion criteria and the exclusion criteria. All patients included were performed with TB-IGRA. For evaluating the diagnostic performance of TB-IGRA, patients were divided into positive TB-IGRA and negative TB-IGRA groups. And all statistical analysis was performed using SPSS Results: Performed by logistic regression analysis, we found that CD4 cell counts is independent risk factor for false negative of TB-IGRA(P<0.001). Additionally, false negative of TB-IGRA were 68.75%, 24.29% and 14.63%, respectively, in the three groups whose CD4+ T cell counts were 100/μL, with the highest frequency in subjects with CD4+ T cell counts <20/μL(P<0.001). And false negative of TB-IGRA were 68.75%, 27.77%, 20.58% and 14.63%, respectively, in the four groups 100/μL (n = 82). The group of CD4+ T cell counts <20/μL had the highest false negative (P100/μL (P=0.483, P=0.623, respectively). Conclusion: The low level of CD4+ T-cell counts increase false negative TB-IGRA in HIV infected patients with active tuberculosis. These data suggest IGRA assays may have unreliable diagnostic performance results among patients with advanced HIV especially CD4+ T cell counts were <20/μL. Infectious Diseases HIV active tuberculosis TB-IGRA CD4 cell counts Figures Figure 1 Introduction Global data in 2017 showed that tuberculosis (TB) caused 10.0 million cases and 1.3 million deaths, and 60% of notified TB patients had a documented human immunodeficiency virus (HIV) test result. Number of 464 633 TB cases among HIV-positive people were reported; of these, 84% were on antiretroviral therapy (ART) [ 1 ]. Advanced immunodeficiency of HIV-infected persons had a greater risk of active TB[ 2 ]. Moreover, tuberculosis is one of the most common diseases resulting in morbidity and mortality in the world[ 1 , 3 ]. The immunodiagnosis for Mycobacterium tuberculosis (MTB) infection diagnosis was a new adjuvant method, and the interferon-gamma release assay (IGRA) was one of the most important advances of immunodiagnosis which has been widely applied and accepted in the clinic[ 4 , 5 ]. Enzyme-linked immunosorbent spot (ELISPOT) assay and enzyme-linked immunosorbent assay (ELISA) to detect IFN-γ released into culture supernatants are two forms of the IGRAs, which using the immunogenic and specific MTB antigens including early secreted antigenic target (ESAT–6) and culture filtrate protein 10kDa (CFP–10) for immunodiagnosis[ 6 , 7 ]. A certain false negative rate had been found in IGRA among patients with tuberculosis especially in HIV infected individuals[ 8 ]. In addition, older age, non-Hispanic white race/ethnicity, being tested with T-SPOT.TB, albumin-globulin ratio, CD4+ and CD8+ had been think as the factors for TB-IGRA diagnosis in previous studies[ 8 , 9 ]. In HIV infected patients without active TB, TB-IGRA assay with MTB specific antigens were negatively correlated to numbers of circulating CD4+ T-cells, and was influenced by the degree of immunodeficiency[ 10 ]. However, the in-depth studies of the IGRA diagnosis in HIV infected patients with active tuberculosis has not been found. The determined diagnosis in HIV infected patients with active tuberculosis is important, and further research is needed. The objectives of this study were to investigate the factors associated with the diagnostic performance of IGRA in HIV infected patients with active tuberculosis. And to determine the impact that differenthierarchy CD4+ T-cell counts towards the performance of the IGRA assay among active tuberculosis patients. Methods Study population All patients (>16 years of age) diagnosed as HIV infected patients with naïve active tuberculosis in the infectious department of Xixi Hospital of Hangzhou in China, who were enrolled from January 1, 2016 to September 1, 2019, were retrospectively included into the study. HIV infection was confirmed in accordance with Centers for Disease Control and Prevention (CDC) definitions. History of AIDS diagnosis was determined according to the AIDS management guidelines[ 11 ]. The patients diagnosed with active TB was based on laboratory data (sputum smear microscopy and/or identification of M. tuberculosis in sputum/blood culture and/or GeneXpert for bronchial lavage). And the diagnosis of pulmonary TB with culture, smear and GeneXpert negativity was based on the combination of signs, symptoms, computed tomography (CT), good response to against TB treatment and the clinician’s opinion. In addition, the diagnosis of extra pulmonary TB with clinically suspected but negative sputum results and normal CT was based on Fine Needle Aspiration Cytology and Pathology. All patients received anti-tuberculosis treatment and had written informed consent. The exclusion criteria were as follows: (1) patients who did not undergo TB-IGRA examination; (2)history of administration of agents with activity against TB treatment; (3) evidence of nontuberculous mycobacteria infection; (4) patients with combined cirrhosis; (6) patients with other immune deficiencies (including malignancy, congenital immunodeficiency and treated with immunosuppressants); and (7) patients with immune reconstitution inflammatory syndrome (IRIS). Clinical biochemical parameters and TB-IGRA assay Laboratory data including white blood cell (WBC), neutrophil counts, lymphocyte counts, red blood cell counts (RBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin (ALB), CD4+cell counts, CD8 cell counts, CD4+ to CD8+ ratio, platelet counts(PLT), platelet distribution width(PDW), alanine transaminase (ALT) and aspartate transaminase (AST) were examined in a central laboratory in our hospital within 12 hours of patient admission. Mycobacterium tuberculosis IFN-γ release assay according to the manufacturer’s instructions using the Wantai quantitative diagnostic kit (WT-IGRA, Beijing Wantai Biological Pharmacy Corporation Ltd). First, BD (American BD company) heparin lithium anticoagulation blood collection tubes were used to extract more than 5 ml of venous blood, anticoagulant dissolved by immediately gently inverting and mixing more than 3 times. Whole blood was collected and dispensed into 3 different culture tubes. “T” was a test culture tube to which tuberculosis specific antigens ESAT–6 and CFP–10 are added; “N” was a bottom control culture tube; “P” was a positive control culture tube with non-specific stimulating antigen phytohemagglutinin (PHA). 1 ml of venous blood was dispensed to each culture tube and mixed it upside down for more than 3 times before dispensing. After the dispensing, the culture tube was gently inverted 5 times, and immediately cultured in a 37 ° C incubator (22 ± 2) h. After standing culture (22 ± 2) h, it was taken out, and the supernatant was collected by centrifugation. Secondly, the content of IFN–7 in the supernatant was quantitatively detected by double antibody sandwich method. Whether or not the positive of M. tuberculosis infection was determined based on the amount of IFN–7 specifically raised in the stimulation culture system. In theory, each subject can respond to the non-specific stimulating antigen PHA. Statistical analysis Discrete data were presented as counts (percentage), and continuous data were presented as the mean ± standard deviation for normally distributed, medians and interquartile ranges for non-normally distributed. The differences between continuous data were tested using the Mann-Whitney U-test (nonparametric) or the Student t test (normally distributed). The differences between categorical data were evaluated using the χ2 test with Continuity correction. P values were evaluated by Bonferroni correction. For predicting false negative rates, we performed univariate and multivariate analyses by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis was conducted to present a varying cut-off values of CD4+ T cell counts for positive TB-IGRA and negative TB-IGRA. All statistical analysis was performed using SPSS, version 19 (SPSS, Armonk, NY, USA), and P < 0.05 was considered statistically significant. Results Clinical data pertaining to HIV-infected patients with active TB between positive TB-IGRA and negative TB-IGRA 184 patients were divided into positive TB-IGRA (n = 133) and negative TB-IGRA (N = 51) groups. The sensitivity of the TB-IGRA was 72.28% among the 184 patients. And clinical characteristics and baseline demographics of the 184 patients between positive TB-IGRA and negative TB-IGRA groups are shown in Table 1. Analysis of positive and negative TB-IGRA performance results, we found that significant difference in CD4+ T-cell counts, CD8 cell counts, CD4+ to CD8+ ratio, ALB, ESR, Lymphocyte count and AST. (P ≤ 0.001; P = 0.001; P ≤ 0.001; P = 0.005; P = 0.047; P = 0.001; P = 0.004, respectively). Univariate and multivariate analyses of the diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis Performed by logistic regression analysis, we determined the value of CD4+ T-cell counts for the diagnostic performance of TB-IGRA. In univariate analysis, CD4 cell counts, CD8 cell counts, CD4+ to CD8+ ratio, ALB, ESR, Lymphocyte count and AST were found to be independent risk factors for false negative of TB-IGRA. In multivariate analysis, we analyzed the CD4 cell counts, CD8 cell counts, CD4+ to CD8+ ratio, ALB, ESR, Lymphocyte count and AST, we found that CD4 cell counts were independent risk factors for false negative of TB-IGRA (Table 2, P = 0.001). Hierarchy low CD4+ T-cell counts in HIV infected patients with active tuberculosis is associated with false negative of TB-IGRA We found the level of CD4+ T-cell counts was significantly lower in negative TB-IGRA group (Fig 1A, P<0.001). Additionally, we obtained an optimal cut-off value (28.5cells/mm3) of CD4+ T-cell counts after ROC analysis. For examining whether hierarchy declines of CD4+ T cells were associated with the diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis, we divided levels of CD4+ T-cell counts into three groups based on: 100/μL (n = 82). And false negative of TB-IGRA were 68.75%, 24.29% and 14.63%, respectively, in the three groups whose CD4+ T cell counts <20/μL had the highest false negative (Fig 1B, P50/μL (n = 116). False negative of TB-IGRA were were 47.05% and 16.38%, (Fig 1C, P<0.001). In addition, we divided levels of CD4+ T-cell counts into four groups based on: 100/μL (n = 82). And false negative of TB-IGRA were 68.75%, 27.77%, 20.58% and 14.63%, respectively, in the four groups whose CD4+ T cell counts <20/μL had the highest false negative (Fig 1D, P100/μL (P = 0.483, P = 0.623, respectively). Discussion Tuberculosis is the leading cause of death among patients co-infected with HIV. And due to a high frequency of smear-negative and high rates of extrapulmonary TB in HIV co-infected people, it is difficult for diagnosis of TB[ 12 ]. In the past two decades, the immune diagnosis of Mycobacterium tuberculosis infection provided rapid and accurate results than traditional laboratory techniques in the fight against TB. However, the diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis was not clear enough. In this study, the sensitivity of the TB-IGRA assay was 72.28% in HIV infected patients with active TB. The sensitivity of the TB-IGRA test in HIV–1 infected persons with active TB was higher than the reported in the studies of Prabhavathi et al[ 13 ], Sauzullo et al[ 14 ] and Takwoingi et al[ 15 ] (54.55%;66%; 67.3%, respectively), and lower than the reported in the studies of Danel et al[ 16 ] and Aichelburg et al[ 17 ] (88.0%; 90.9%, respectively). And we evaluate the sensitivity of IGRA test in HIV infected patients with active TB is approximately 60%–90% in studies using a large number of samples; it may be different in studies with a small number of samples. A similar results of the TB-IGRA was reported by Yu et al that TB-IGRA test were affected by the level of low CD4(+) cell counts[ 18 ]. However, hierarchy of CD4+ T-cell counts was not used for further explanation. In our study, CD4+ T-cell counts were divided into three groups of 100/μL. And we found that the groups of CD4+ T-cell counts <20/μL in HIV infected patients with active tuberculosis had a high false negative 68.75% of TB-IGRA. And there were significant differences compared with the groups whose CD4+ T cell counts were 20–100/μL and >100/μL; 20–50/μL, 51–100/μL and >100/μL. Moreover, there were no significant differences in groups of 20–100/μL and >100/μL; 20–50/μL, 51–100/μL and >100/μL. These data suggest that IGRA may have unreliable diagnostic performance results among advanced HIV patients with active tuberculosis whose CD4+ T cell counts were 20/μL. Dheda et al, Cattamanchi et al and Cai et al suggested that IGRA B positive rates was not affected by CD4+ T-cell depletion in HIV infection and active TB [ 19–21 ]. But they used an ELISPOT-based IGRA that was not same as our methods. The study of Ahamed et al suggested that no significant difference in CD4 count between QFT-G positive and negative subjects but they also suggested that the sensitivity of the assay was impaired when CD4 count <200 cells/µl in HIV patients with active TB [ 22 ]. Our results strongly support Leidl et al that showed QuantiFERON-TB Gold In-Tube (QFT-G-IT) positive rates are correlated with T-cell stratification in patients with HIV-infection and active TB whose CD4+ T-cells counts of >250, 100–250 and <100 /μL[ 10 ]. And we made more detailed in T-cell stratification. There are some limitations in our study. The diagnosis of active TB in patients including smear and culture negative results, was made only by clinical and radiology. However, the positive rate of smear and culture is low for diagnosis of active TB and we found good response to anti-TB treatment from enrolled patients by following up. Another limitation of our study is it did not report the specificity of TB-IGRA since we did not get the subjects of HIV positive TB negative individuals in our population. Conclusions The low level of CD4+ T-cell counts increase false negative TB-IGRA in HIV infected patients with active tuberculosis. These data suggest IGRA assays may have unreliable diagnostic performance results among advanced HIV patients with active TB whose CD4+ T cell counts were <20/μL. List of Abbreviations IGRA, interferon-gamma release assay; TB, tuberculosis; HIV, human immunodeficiency virus; ART, antiretroviral therapy; MTB, Mycobacterium tuberculosis; WBC, white blood cell; RBC, red blood cell counts; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ALB, albumin; PLT, platelet counts; PDW, platelet distribution width; ALT, alanine transaminase; AST, aspartate transaminase. Declarations Funding This work was supported by the Hangzhou Science and Technology Bureau [grant numbers20170533B81] and Zhejiang Medical Association Clinical Infection Research Project [grant numbers 2016ZYC-A42]. The funding body had no role in the design of the study and collection, analysis, interpretation of data or preparation of the manuscript. Availability of data and materials The datasets used and/or analysed during the current study are available from the first author on reasonable request. Authors’ contributions M. Y. W. designed research; performed research; analysed data and wrote the manuscript. J. T. C. collected the data and modified the manuscript. X. T.D cleaned and analysed the data. Z. D. Z. and J. H. Y. contributed to project conception, data analysis interpretation, and manuscript preparation. J. C. S. and J. Y. contributed to data analysis interpretation and manuscript preparation. Ethics approval and consent to participate All patients provided written informed consent and this study was approved by Ethics Committee of Xixi Hospital of Hangzhou in China. All procedures and methods were performed in accordance with the relevant international guidelines and regulations in order to reduce physical discomfort of the subjects. Consent for publication Not applicable Competing interests The authors declare that they have no competing interests. References 1.Organization WH. Global Tuberculosis Report 2018. 2018. 2.Antonucci G, Girardi E, Raviglione MC, Ippolito G. Risk factors for tuberculosis in HIV-infected persons. A prospective cohort study. The Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA). JAMA.1995; 274(2):143–148. 3.Wang L, Zhang H, Ruan Y, Chin DP, Xia Y, Cheng S, Chen M, Zhao Y, Jiang S, Du X, et al. Tuberculosis prevalence in China, 1990–2010; a longitudinal analysis of national survey data. 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Relationship between T-SPOT.TB responses and numbers of circulating CD4+ T-cells in HIV infected patients with active tuberculosis. Biosci Trends.2014; 8(3):163–168. 21.Dheda K, Lalvani A, Miller RF, Scott G, Booth H, Johnson MA, Zumla A, Rook GA. Performance of a T-cell-based diagnostic test for tuberculosis infection in HIV-infected individuals is independent of CD4 cell count. AIDS.2005; 19(17):2038–2041. 22.Syed Ahamed Kabeer B, Sikhamani R, Swaminathan S, Perumal V, Paramasivam P, Raja A. Role of interferon gamma release assay in active TB diagnosis among HIV infected individuals. PLoS One.2009; 4(5):e5718. Tables Table 1. Clinical data analyses in HIV-infected patients with active TB between positive TB-IGRA and negative TB-IGRA. Positive TB-IGRA Negative TB-IGRA p -value Subjects ( n ) 133 51 NA Male/female 119/14 45/6 0.809 Median Age, year 41(16-86) 39(23-74) 0.548 Median CD4+ T cell counts, / μ L 108(0-797) 25(0-700) <0.001 Median CD8+ T cell counts, / μ L 541(40-2078) 354(74-1805) 0.001 CD4+ to CD8+ ratio 0.33(0-3.92) 0.05(0-0.67) <0.001 CRP, mg/dl 46.00(0.40-209.80) 35.00(0.39-203.00) 0.532 ALB, g/l 31.6(14.8-50.5) 27.5(16.3-49.4) 0.005 ESR, mm/h 62.90±31.26 74.73±35.91 0.047 WBC,10^9/L 5.54(0-12.21) 5.66(1.80-33.00) 0.894 Neutrophil counts ,10^9/L 3.81(0.35-61.20) 4.07(1.12-29.60) 0.233 Lymphocyte counts ,10^9/L 1.02(0-2.99) 0.68(0.07-3.94) 0.001 RBC,10^12/L 3.65±0.82 3.54±0.79 0.391 PLT,10^9/L 242.50(7.90-266.00) 255.00(3.50-477.00) 0.628 PDW, fl 11.10(7.60-106.00) 11.10(7.20-21.60) 0.936 ALT, U/L 21(4-667) 22(7-190) 0.326 AST, U/L 27(8-542) 40(10-139) 0.004 Patients on HARRT, n (%) 62 22 0.671 HIV-1 viral load, copies/mL 0.282 ≥ 10 0 copies/mL 82 27 <100 copies/mL 51 24 TB disease Pulmonary 72 25 0.104 Extrapulmonary 15 12 Pulmonary and extrapulmonary 46 14 A cid -fast staining method (n) 38 13 0.840 Pathology(n) 11 2 0.520 Table 2 . Univariate and multivariate analyses of the diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis. Odds ratio 95% CI P value Univariate analysis CD4 cell count , / μ L 1.006 1.003-1.010 0.001 CD8 cell count, / μ L 1.002 1.001-1.003 0.004 CD4+ to CD8+ ratio 40.189 3.925-411.482 0.002 ALB , g/l 1.070 1.018-1.124 0.008 ESR, mm/h 0.989 0.979-0.999 0.031 Lymphocyte count , 10^9/L 2.379 1.271-4.452 0.007 AST, U/L 0.999 0.994-1.004 0.671 Multivariate analysis CD4 cell count, / μ L 1.006 1.003-1.010 0.001 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6907","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":191644,"identity":"09c3056f-5dea-4d72-adcc-901d216df9c5","order_by":1,"name":"Mengyan Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIie3RMWoDMRBA0TED2macbWVCqlxAsGAMDuQqEoZ1E1K7CERgUEq39jl8gVkEqRS2deHa9eYCJrKrVIrSBaLfDcxDQgIolf5gNSLzoM5YA+g4489k8iZMt11xNbG5RPV07ylwrfg6ZxDwBN3OHW+bnk8SVnNjqw9OitF6zPzpTs2UuZUQlsbSs04SxBsdT8HFtLOtHDlvrCSVJAJJ+bHD1/0aIjlnELoQCh6VuBCbQSQKHR+5RRlgMdPvy8bRU5o89t4Pg3rAehPMYXiZ322qkCbf76ivnyly92MV/2K5VCqV/lNfDftIDO+AoAkAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-8813-2555","institution":"Zhejiang University School of Medicine First Affiliated Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Mengyan","middleName":"","lastName":"Wang","suffix":""},{"id":191645,"identity":"ffba81fa-53cd-4500-aecc-a111bdb393b7","order_by":2,"name":"Tongtong Chen","email":"","orcid":"","institution":"Zhejiang Chinese Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tongtong","middleName":"","lastName":"Chen","suffix":""},{"id":191646,"identity":"37bc3bfb-67eb-4298-944d-c2b739801d25","order_by":3,"name":"Xiaotian Dong","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaotian","middleName":"","lastName":"Dong","suffix":""},{"id":191647,"identity":"77152c68-0a4f-4e21-a1a8-81b52a6d0976","order_by":4,"name":"Zhongdong Zhang","email":"","orcid":"","institution":"Xixi hospital of Hangzhou","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhongdong","middleName":"","lastName":"Zhang","suffix":""},{"id":191648,"identity":"611cc2da-257f-4a52-a7e2-c6445be3bac2","order_by":5,"name":"Jinchuan Shi","email":"","orcid":"","institution":"Xixi hospital of Hangzhou","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jinchuan","middleName":"","lastName":"Shi","suffix":""},{"id":191649,"identity":"828ba58f-98a7-4f27-9e8c-a4a44430c0e1","order_by":6,"name":"Jun Yan","email":"","orcid":"","institution":"Xixi hospital of Hangzhou","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Yan","suffix":""},{"id":191650,"identity":"8234b117-fbfc-49a0-b400-8aa0b77d5693","order_by":7,"name":"Jianhua Yu","email":"","orcid":"","institution":"Xixi hospital of Hangzhou","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianhua","middleName":"","lastName":"Yu","suffix":""}],"badges":[],"createdAt":"2019-10-16 13:02:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.2.16261/v1","doiUrl":"https://doi.org/10.21203/rs.2.16261/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":134728,"identity":"b20ecbd6-f9b3-45c6-877d-b8480197ce16","added_by":"auto","created_at":"2019-10-21 22:37:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":147831,"visible":true,"origin":"","legend":"","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/fcebc627-01b0-4810-960d-601b60348159/v1/Fig1.jpg"},{"id":13477464,"identity":"e6e85634-d944-4430-a11a-51f069d5ef02","added_by":"auto","created_at":"2021-09-16 21:31:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":416763,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6907/v1/c7a6994c-734e-4ac6-baee-146db6cd9fb2.pdf"}],"financialInterests":"","formattedTitle":"The diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis is associated with CD4+ T-cell counts","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlobal data in 2017 showed that tuberculosis (TB) caused 10.0 million cases and 1.3 million deaths, and 60% of notified TB patients had a documented human immunodeficiency virus (HIV) test result. Number of 464 633 TB cases among HIV-positive people were reported; of these, 84% were on antiretroviral therapy (ART) [\u003ca href=\"#_ENREF_1\"\u003e1\u003c/a\u003e]. Advanced immunodeficiency of HIV-infected persons had a greater risk of active TB[\u003ca href=\"#_ENREF_2\"\u003e2\u003c/a\u003e]. Moreover, tuberculosis is one of the most common diseases resulting in morbidity and mortality in the world[\u003ca href=\"#_ENREF_1\"\u003e1\u003c/a\u003e, \u003ca href=\"#_ENREF_3\"\u003e3\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eThe immunodiagnosis for Mycobacterium tuberculosis (MTB) infection diagnosis was a new adjuvant method, and the interferon-gamma release assay (IGRA) was one of the most important advances of immunodiagnosis which has been widely applied and accepted in the clinic[\u003ca href=\"#_ENREF_4\"\u003e4\u003c/a\u003e, \u003ca href=\"#_ENREF_5\"\u003e5\u003c/a\u003e]. Enzyme-linked immunosorbent spot (ELISPOT) assay and enzyme-linked immunosorbent assay (ELISA) to detect IFN-γ released into culture supernatants are two forms of the IGRAs, which using the immunogenic and specific MTB antigens including early secreted antigenic target (ESAT–6) and culture filtrate protein 10kDa (CFP–10) for immunodiagnosis[\u003ca href=\"#_ENREF_6\"\u003e6\u003c/a\u003e, \u003ca href=\"#_ENREF_7\"\u003e7\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eA certain false negative rate had been found in IGRA among patients with tuberculosis especially in HIV infected individuals[\u003ca href=\"#_ENREF_8\"\u003e8\u003c/a\u003e]. In addition, older age, non-Hispanic white race/ethnicity, being tested with T-SPOT.TB, albumin-globulin ratio, CD4+ and CD8+ had been think as the factors for TB-IGRA diagnosis in previous studies[\u003ca href=\"#_ENREF_8\"\u003e8\u003c/a\u003e, \u003ca href=\"#_ENREF_9\"\u003e9\u003c/a\u003e]. In HIV infected patients without active TB, TB-IGRA assay with MTB specific antigens were negatively correlated to numbers of circulating CD4+ T-cells, and was influenced by the degree of immunodeficiency[\u003ca href=\"#_ENREF_10\"\u003e10\u003c/a\u003e]. However, the in-depth studies of the IGRA diagnosis in HIV infected patients with active tuberculosis has not been found.\u003c/p\u003e\n\u003cp\u003eThe determined diagnosis in HIV infected patients with active tuberculosis is important, and further research is needed. The objectives of this study were to investigate the factors associated with the diagnostic performance of IGRA in HIV infected patients with active tuberculosis. And to determine the impact that differenthierarchy CD4+ T-cell counts towards the performance of the IGRA assay among active tuberculosis patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cp\u003eAll patients (\u0026gt;16 years of age) diagnosed as HIV infected patients with naïve active tuberculosis in the infectious department of Xixi Hospital of Hangzhou in China, who were enrolled from January 1, 2016 to September 1, 2019, were retrospectively included into the study. HIV infection was confirmed in accordance with Centers for Disease Control and Prevention (CDC) definitions. History of AIDS diagnosis was determined according to the AIDS management guidelines[\u003ca href=\"#_ENREF_11\"\u003e11\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eThe patients diagnosed with active TB was based on laboratory data (sputum smear microscopy and/or identification of M. tuberculosis in sputum/blood culture and/or GeneXpert for bronchial lavage). And the diagnosis of pulmonary TB with culture, smear and GeneXpert negativity was based on the combination of signs, symptoms, computed tomography (CT), good response to against TB treatment and the clinician’s opinion. In addition, the diagnosis of extra pulmonary TB with clinically suspected but negative sputum results and normal CT was based on Fine Needle Aspiration Cytology and Pathology. All patients received anti-tuberculosis treatment and had written informed consent.\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria were as follows: (1) patients who did not undergo TB-IGRA examination; (2)history of administration of agents with activity against TB treatment; (3) evidence of nontuberculous mycobacteria infection; (4) patients with combined cirrhosis; (6) patients with other immune deficiencies (including malignancy, congenital immunodeficiency and treated with immunosuppressants); and (7) patients with immune reconstitution inflammatory syndrome (IRIS).\u003c/p\u003e\n\u003ch3\u003eClinical biochemical parameters and TB-IGRA assay\u003c/h3\u003e\n\u003cp\u003eLaboratory data including white blood cell (WBC), neutrophil counts, lymphocyte counts, red blood cell counts (RBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin (ALB), CD4+cell counts, CD8 cell counts, CD4+ to CD8+ ratio, platelet counts(PLT), platelet distribution width(PDW), alanine transaminase (ALT) and aspartate transaminase (AST) were examined in a central laboratory in our hospital within 12 hours of patient admission.\u003c/p\u003e\n\u003cp\u003eMycobacterium tuberculosis IFN-γ release assay according to the manufacturer’s instructions using the Wantai quantitative diagnostic kit (WT-IGRA, Beijing Wantai Biological Pharmacy Corporation Ltd). First, BD (American BD company) heparin lithium anticoagulation blood collection tubes were used to extract more than 5 ml of venous blood, anticoagulant dissolved by immediately gently inverting and mixing more than 3 times. Whole blood was collected and dispensed into 3 different culture tubes. “T” was a test culture tube to which tuberculosis specific antigens ESAT–6 and CFP–10 are added; “N” was a bottom control culture tube; “P” was a positive control culture tube with non-specific stimulating antigen phytohemagglutinin (PHA). 1 ml of venous blood was dispensed to each culture tube and mixed it upside down for more than 3 times before dispensing. After the dispensing, the culture tube was gently inverted 5 times, and immediately cultured in a 37 ° C incubator (22 ± 2) h. After standing culture (22 ± 2) h, it was taken out, and the supernatant was collected by centrifugation. Secondly, the content of IFN–7 in the supernatant was quantitatively detected by double antibody sandwich method. Whether or not the positive of M. tuberculosis infection was determined based on the amount of IFN–7 specifically raised in the stimulation culture system. In theory, each subject can respond to the non-specific stimulating antigen PHA.\u003c/p\u003e\n\u003ch3\u003eStatistical analysis\u003c/h3\u003e\n\u003cp\u003eDiscrete data were presented as counts (percentage), and continuous data were presented as the mean ± standard deviation for normally distributed, medians and interquartile ranges for non-normally distributed. The differences between continuous data were tested using the Mann-Whitney U-test (nonparametric) or the Student t test (normally distributed). The differences between categorical data were evaluated using the χ2 test with Continuity correction. P values were evaluated by Bonferroni correction. For predicting false negative rates, we performed univariate and multivariate analyses by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis was conducted to present a varying cut-off values of CD4+ T cell counts for positive TB-IGRA and negative TB-IGRA. All statistical analysis was performed using SPSS, version 19 (SPSS, Armonk, NY, USA), and P \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003ch3\u003eClinical data pertaining to HIV-infected patients with active TB between positive TB-IGRA and negative TB-IGRA\u003c/h3\u003e\n\u003cp\u003e184 patients were divided into positive TB-IGRA (n = 133) and negative TB-IGRA (N = 51) groups. The sensitivity of the TB-IGRA was 72.28% among the 184 patients. And clinical characteristics and baseline demographics of the 184 patients between positive TB-IGRA and negative TB-IGRA groups are shown in Table 1. Analysis of positive and negative TB-IGRA performance results, we found that significant difference in CD4+ T-cell counts, CD8 cell counts, CD4+ to CD8+ ratio, ALB, ESR, Lymphocyte count and AST. (P ≤ 0.001; P = 0.001; P ≤ 0.001; P = 0.005; P = 0.047; P = 0.001; P = 0.004, respectively).\u003c/p\u003e\n\u003ch3\u003eUnivariate and multivariate analyses of the diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis\u003c/h3\u003e\n\u003cp\u003ePerformed by logistic regression analysis, we determined the value of CD4+ T-cell counts for the diagnostic performance of TB-IGRA. In univariate analysis, CD4 cell counts, CD8 cell counts, CD4+ to CD8+ ratio, ALB, ESR, Lymphocyte count and AST were found to be independent risk factors for false negative of TB-IGRA. In multivariate analysis, we analyzed the CD4 cell counts, CD8 cell counts, CD4+ to CD8+ ratio, ALB, ESR, Lymphocyte count and AST, we found that CD4 cell counts were independent risk factors for false negative of TB-IGRA (Table 2, P = 0.001).\u003c/p\u003e\n\u003ch3\u003eHierarchy low CD4+ T-cell counts in HIV infected patients with active tuberculosis is associated with false negative of TB-IGRA\u003c/h3\u003e\n\u003cp\u003eWe found the level of CD4+ T-cell counts was significantly lower in negative TB-IGRA group (Fig 1A, P\u0026lt;0.001). Additionally, we obtained an optimal cut-off value (28.5cells/mm3) of CD4+ T-cell counts after ROC analysis. For examining whether hierarchy declines of CD4+ T cells were associated with the diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis, we divided levels of CD4+ T-cell counts into three groups based on: \u0026lt;20/μL (n = 32), 20–100/μL (n = 70) and \u0026gt;100/μL (n = 82). And false negative of TB-IGRA were 68.75%, 24.29% and 14.63%, respectively, in the three groups whose CD4+ T cell counts \u0026lt;20/μL had the highest false negative (Fig 1B, P\u0026lt;0.001). And we divided levels of CD4+ T-cell counts into two groups based on: ≤50/μL (n = 68) and \u0026gt;50/μL (n = 116). False negative of TB-IGRA were were 47.05% and 16.38%, (Fig 1C, P\u0026lt;0.001). In addition, we divided levels of CD4+ T-cell counts into four groups based on: \u0026lt;20/μL (n = 32), 20–50/μL (n = 36), 51–100/μL (n = 34) and \u0026gt;100/μL (n = 82). And false negative of TB-IGRA were 68.75%, 27.77%, 20.58% and 14.63%, respectively, in the four groups whose CD4+ T cell counts \u0026lt;20/μL had the highest false negative (Fig 1D, P\u0026lt;0.001). There was no significant difference in the groups of 20–50/μL, 51–100/μL and \u0026gt;100/μL (P = 0.483, P = 0.623, respectively).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTuberculosis is the leading cause of death among patients co-infected with HIV. And due to a high frequency of smear-negative and high rates of extrapulmonary TB in HIV co-infected people, it is difficult for diagnosis of TB[\u003ca href=\"#_ENREF_12\"\u003e12\u003c/a\u003e]. In the past two decades, the immune diagnosis of Mycobacterium tuberculosis infection provided rapid and accurate results than traditional laboratory techniques in the fight against TB. However, the diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis was not clear enough.\u003c/p\u003e\n\u003cp\u003eIn this study, the sensitivity of the TB-IGRA assay was 72.28% in HIV infected patients with active TB. The sensitivity of the TB-IGRA test in HIV–1 infected persons with active TB was higher than the reported in the studies of Prabhavathi et al[\u003ca href=\"#_ENREF_13\"\u003e13\u003c/a\u003e], Sauzullo et al[\u003ca href=\"#_ENREF_14\"\u003e14\u003c/a\u003e] and Takwoingi et al[\u003ca href=\"#_ENREF_15\"\u003e15\u003c/a\u003e] (54.55%;66%; 67.3%, respectively), and lower than the reported in the studies of Danel et al[\u003ca href=\"#_ENREF_16\"\u003e16\u003c/a\u003e] and Aichelburg et al[\u003ca href=\"#_ENREF_17\"\u003e17\u003c/a\u003e] (88.0%; 90.9%, respectively). And we evaluate the sensitivity of IGRA test in HIV infected patients with active TB is approximately 60%–90% in studies using a large number of samples; it may be different in studies with a small number of samples.\u003c/p\u003e\n\u003cp\u003eA similar results of the TB-IGRA was reported by Yu et al that TB-IGRA test were affected by the level of low CD4(+) cell counts[\u003ca href=\"#_ENREF_18\"\u003e18\u003c/a\u003e]. However, hierarchy of CD4+ T-cell counts was not used for further explanation. In our study, CD4+ T-cell counts were divided into three groups of \u0026lt;20/μL, 20–100/μL and \u0026gt;100/μL. And we found that the groups of CD4+ T-cell counts \u0026lt;20/μL in HIV infected patients with active tuberculosis had a high false negative 68.75% of TB-IGRA. And there were significant differences compared with the groups whose CD4+ T cell counts were 20–100/μL and \u0026gt;100/μL; 20–50/μL, 51–100/μL and \u0026gt;100/μL. Moreover, there were no significant differences in groups of 20–100/μL and \u0026gt;100/μL; 20–50/μL, 51–100/μL and \u0026gt;100/μL. These data suggest that IGRA may have unreliable diagnostic performance results among advanced HIV patients with active tuberculosis whose CD4+ T cell counts were \u0026lt;20/μL. But IGRA may had the value of assisted diagnosis with advanced HIV patients with active tuberculosis whose CD4+ T cell counts were \u0026gt;20/μL.\u003c/p\u003e\n\u003cp\u003eDheda et al, Cattamanchi et al and Cai et al suggested that IGRA B positive rates was not affected by CD4+ T-cell depletion in HIV infection and active TB [\u003ca href=\"#_ENREF_19\"\u003e19–21\u003c/a\u003e]. But they used an ELISPOT-based IGRA that was not same as our methods. The study of Ahamed et al suggested that no significant difference in CD4 count between QFT-G positive and negative subjects but they also suggested that the sensitivity of the assay was impaired when CD4 count \u0026lt;200 cells/µl in HIV patients with active TB [\u003ca href=\"#_ENREF_22\"\u003e22\u003c/a\u003e]. Our results strongly support Leidl et al that showed QuantiFERON-TB Gold In-Tube (QFT-G-IT) positive rates are correlated with T-cell stratification in patients with HIV-infection and active TB whose CD4+ T-cells counts of \u0026gt;250, 100–250 and \u0026lt;100 /μL[\u003ca href=\"#_ENREF_10\"\u003e10\u003c/a\u003e]. And we made more detailed in T-cell stratification.\u003c/p\u003e\n\u003cp\u003eThere are some limitations in our study. The diagnosis of active TB in patients including smear and culture negative results, was made only by clinical and radiology. However, the positive rate of smear and culture is low for diagnosis of active TB and we found good response to anti-TB treatment from enrolled patients by following up. Another limitation of our study is it did not report the specificity of TB-IGRA since we did not get the subjects of HIV positive TB negative individuals in our population.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe low level of CD4+ T-cell counts increase false negative TB-IGRA in HIV infected patients with active tuberculosis. These data suggest IGRA assays may have unreliable diagnostic performance results among advanced HIV patients with active TB whose CD4+ T cell counts were \u0026lt;20/μL.\u003c/p\u003e\n"},{"header":"List of Abbreviations","content":"\u003cp\u003eIGRA, interferon-gamma release assay; TB, tuberculosis; HIV, human immunodeficiency virus; ART, antiretroviral therapy; MTB, Mycobacterium tuberculosis; WBC, white blood cell; RBC, red blood cell counts; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ALB, albumin; PLT, platelet counts; PDW, platelet distribution width; ALT, alanine transaminase; AST, aspartate transaminase.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis work was supported by the Hangzhou Science and Technology Bureau [grant numbers20170533B81] and Zhejiang Medical Association Clinical Infection Research Project [grant numbers 2016ZYC-A42]. The funding body had no role in the design of the study and collection, analysis, interpretation of data or preparation of the manuscript.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the first author on reasonable request.\u003c/p\u003e\n\u003ch2\u003eAuthors’ contributions\u003c/h2\u003e\n\u003cp\u003eM. Y. W. designed research; performed research; analysed data and wrote the manuscript. J. T. C. collected the data and modified the manuscript. X. T.D cleaned and analysed the data. Z. D. Z. and J. H. Y. contributed to project conception, data analysis interpretation, and manuscript preparation. J. C. S. and J. Y. contributed to data analysis interpretation and manuscript preparation.\u003c/p\u003e\n\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eAll patients provided written informed consent and this study was approved by Ethics Committee of Xixi Hospital of Hangzhou in China. All procedures and methods were performed in accordance with the relevant international guidelines and regulations in order to reduce physical discomfort of the subjects.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1.Organization WH. Global Tuberculosis Report 2018. 2018.\u003c/p\u003e\n\u003cp\u003e2.Antonucci G, Girardi E, Raviglione MC, Ippolito G. Risk factors for tuberculosis in HIV-infected persons. A prospective cohort study. The Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA). JAMA.1995; 274(2):143–148.\u003c/p\u003e\n\u003cp\u003e3.Wang L, Zhang H, Ruan Y, Chin DP, Xia Y, Cheng S, Chen M, Zhao Y, Jiang S, Du X, et al. Tuberculosis prevalence in China, 1990–2010; a longitudinal analysis of national survey data. Lancet.2014; 383(9934):2057–2064.\u003c/p\u003e\n\u003cp\u003e4.Doan TN, Eisen DP, Rose MT, Slack A, Stearnes G, McBryde ES. Interferon-gamma release assay for the diagnosis of latent tuberculosis infection: A latent-class analysis. PLoS One.2017; 12(11):e0188631.\u003c/p\u003e\n\u003cp\u003e5.Klautau GB, da Mota NVF, Salles MJC, Burattini MN, Rodrigues DS. Interferon-gamma release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study. BMC Infect Dis.2018; 18(1):585.\u003c/p\u003e\n\u003cp\u003e6.Connell TG, Rangaka MX, Curtis N, Wilkinson RJ. QuantiFERON-TB Gold: state of the art for the diagnosis of tuberculosis infection? Expert review of molecular diagnostics.2006; 6(5):663–677.\u003c/p\u003e\n\u003cp\u003e7.Whitworth HS, Scott M, Connell DW, Donges B, Lalvani A. IGRAs—the gateway to T cell based TB diagnosis. Methods.2013; 61(1):52–62.\u003c/p\u003e\n\u003cp\u003e8.Nguyen DT, Teeter LD, Graves J, Graviss EA. Characteristics Associated with Negative Interferon-gamma Release Assay Results in Culture-Confirmed Tuberculosis Patients, Texas, USA, 2013–2015. Emerg Infect Dis.2018; 24(3):534–540.\u003c/p\u003e\n\u003cp\u003e9.Li K, Yang C, Jiang Z, Liu S, Liu J, Fan C, Li T, Dong X. Quantitative investigation of factors relevant to the T cell spot test for tuberculosis infection in active tuberculosis. BMC Infect Dis.2019; 19(1):673.\u003c/p\u003e\n\u003cp\u003e10.Leidl L, Mayanja-Kizza H, Sotgiu G, Baseke J, Ernst M, Hirsch C, Goletti D, Toossi Z, Lange C. Relationship of immunodiagnostic assays for tuberculosis and numbers of circulating CD4+ T-cells in HIV infection. Eur Respir J.2010; 35(3):619–626.\u003c/p\u003e\n\u003cp\u003e11.[Chinese guidelines for diagnosis and treatment of HIV/AIDS (2018)]. Zhonghua Nei Ke Za Zhi.2018; 57(12):867–884.\u003c/p\u003e\n\u003cp\u003e12.Mendez-Samperio P. Diagnosis of Tuberculosis in HIV Co-infected Individuals: Current Status, Challenges and Opportunities for the Future. Scand J Immunol.2017; 86(2):76–82.\u003c/p\u003e\n\u003cp\u003e13.Prabhavathi M, Ahamed Kabeer BS, Deenadayalan A, Raja A. In vitro QuantiFERON-TB gold antigen specific interleukin–1beta to diagnose TB among HIV-positive subjects. Tuberculosis (Edinburgh, Scotland).2016; 96:27–30.\u003c/p\u003e\n\u003cp\u003e14.Sauzullo I, Mengoni F, Ermocida A, Massetti AP, D’Agostino C, Russo G, Salotti A, Falciano M, Vullo V, Mastroianni CM. Interferon-gamma release assay in HIV-infected patients with active tuberculosis: impact of antituberculous drugs on host immune response. New Microbiol.2014; 37(2):153–161.\u003c/p\u003e\n\u003cp\u003e15.Takwoingi Y, Whitworth H, Rees-Roberts M, Badhan A, Partlett C, Green N, Boakye A, Lambie H, Marongiu L, Jit M, et al. Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation. Health Technol Assess.2019; 23(23):1–152.\u003c/p\u003e\n\u003cp\u003e16.Danel C, Kabran M, Inwoley A, Badje A, Herrmann JL, Moh R, Lecarrou J, Gabillard D, Ntakpe JB, Deschamps N, et al. Quantiferon-TB Gold: performance for ruling out active tuberculosis in HIV-infected adults with high CD4 count in Cote d’Ivoire, West Africa. PLoS One.2014; 9(10):e107245.\u003c/p\u003e\n\u003cp\u003e17.Aichelburg MC, Rieger A, Breitenecker F, Pfistershammer K, Tittes J, Eltz S, Aichelburg AC, Stingl G, Makristathis A, Kohrgruber N. Detection and prediction of active tuberculosis disease by a whole-blood interferon-gamma release assay in HIV–1-infected individuals. Clin Infect Dis.2009; 48(7):954–962.\u003c/p\u003e\n\u003cp\u003e18.Yu L, Mo P, Wei Z, Fu R, Yang M, Ji B, Wang J, Li S, Strong AJ, Touzjian N, et al. Development and evaluation of a new interferon-gamma release assay for the diagnosis of tuberculosis infection in HIV-infected individuals in China. Infectious diseases (London, England).2015; 47(4):237–243.\u003c/p\u003e\n\u003cp\u003e19.Cattamanchi A, Ssewenyana I, Davis JL, Huang L, Worodria W, den Boon S, Yoo S, Andama A, Hopewell PC, Cao H. Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection. BMC Infect Dis.2010; 10:75.\u003c/p\u003e\n\u003cp\u003e20.Cai R, Chen J, Guan L, Sun M, Sun Y, Shen Y, Zhang R, Liu L, Lu H. Relationship between T-SPOT.TB responses and numbers of circulating CD4+ T-cells in HIV infected patients with active tuberculosis. Biosci Trends.2014; 8(3):163–168.\u003c/p\u003e\n\u003cp\u003e21.Dheda K, Lalvani A, Miller RF, Scott G, Booth H, Johnson MA, Zumla A, Rook GA. Performance of a T-cell-based diagnostic test for tuberculosis infection in HIV-infected individuals is independent of CD4 cell count. AIDS.2005; 19(17):2038–2041.\u003c/p\u003e\n\u003cp\u003e22.Syed Ahamed Kabeer B, Sikhamani R, Swaminathan S, Perumal V, Paramasivam P, Raja A. Role of interferon gamma release assay in active TB diagnosis among HIV infected individuals. PLoS One.2009; 4(5):e5718.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: white;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eTable 1. Clinical data analyses in HIV-infected patients with active TB between positive TB-IGRA and negative TB-IGRA.\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 425.25pt; border-collapse: collapse; border: none; margin-left: 6.75pt; margin-right: 6.75pt;\" width=\"567\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePositive \u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eTB-IGRA\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eNegative \u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eTB-IGRA\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ep\u003c/span\u003e\u003c/em\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e-value\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eSubjects (\u003cem\u003en\u003c/em\u003e)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e133\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e51\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eNA\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eMale/female\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e119/14\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e45/6\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.809\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eMedian Age, year\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e41(16-86)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e39(23-74)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.548\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eMedian CD4+ T cell counts, /\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026mu;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eL\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e108(0-797)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e25(0-700)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eMedian CD8+ T cell counts, /\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026mu;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eL\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e541(40-2078)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e354(74-1805)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.001\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCD4+ to CD8+ ratio\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.33(0-3.92)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.05(0-0.67)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCRP, mg/dl\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e46.00(0.40-209.80)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e35.00(0.39-203.00)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.532\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eALB, g/l\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e31.6(14.8-50.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e27.5(16.3-49.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.005\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eESR, mm/h\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e62.90\u0026plusmn;31.26\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e74.73\u0026plusmn;35.91\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.047\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eWBC,10^9/L\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e5.54(0-12.21)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e5.66(1.80-33.00)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.894\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eNeutrophil counts\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e,10^9/L\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e3.81(0.35-61.20)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e4.07(1.12-29.60)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.233\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eLymphocyte counts\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e,10^9/L\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.02(0-2.99)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.68(0.07-3.94)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.001\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eRBC,10^12/L\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e3.65\u0026plusmn;0.82\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e3.54\u0026plusmn;0.79\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.391\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePLT,10^9/L\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e242.50(7.90-266.00)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e255.00(3.50-477.00)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.628\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePDW, fl\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e11.10(7.60-106.00)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e11.10(7.20-21.60)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.936\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eALT, U/L\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e21(4-667)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e22(7-190)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.326\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eAST, U/L\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e27(8-542)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e40(10-139)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.004\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePatients on HARRT, n (%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e62\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e22\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.671\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eHIV-1 viral load, copies/mL\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" rowspan=\"3\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.282\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp style=\"text-indent: 24.0pt;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026ge;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e10\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0 copies/mL\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e82\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e27\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp style=\"text-indent: 24.0pt;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026lt;100 copies/mL \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e51\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e24\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eTB disease\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp style=\"text-indent: 24.0pt;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePulmonary\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e72\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e25\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" rowspan=\"3\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.104\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp style=\"text-indent: 24.0pt;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eExtrapulmonary\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e15\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e12\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp style=\"margin-left: 21.0pt;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePulmonary and extrapulmonary\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e46\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e14\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eA\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ecid\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e-fast staining method\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e(n)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e38\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e13\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.840\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 147.95pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"197\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePathology(n)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e11\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.7pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e2\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 51.9pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"69\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.520\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eTable 2\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e. Univariate and multivariate analyses of the diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis.\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eOdds ratio\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e95% CI\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eP \u003c/span\u003e\u003c/em\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003evalue\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eUnivariate analysis\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCD4 cell count\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e, /\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026mu;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eL\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.006\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.003-1.010\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.001\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCD8 cell count, /\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026mu;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eL\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.002\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.001-1.003\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.004\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCD4+ to CD8+ ratio\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e40.189\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e3.925-411.482\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.002\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eALB\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e, g/l\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.070\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.018-1.124\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.008\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eESR, mm/h\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.989\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.979-0.999\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.031\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eLymphocyte count\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e, 10^9/L\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e2.379\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.271-4.452\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.007\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eAST, U/L\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.999\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.994-1.004\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.671\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eMultivariate analysis\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 141.5pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"189\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCD4 cell count, /\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026mu;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eL\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 99.25pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"132\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.006\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 106.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"142\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.003-1.010\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.001\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"HIV, active tuberculosis, TB-IGRA, CD4 cell counts","lastPublishedDoi":"10.21203/rs.2.16261/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.16261/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective: To investigate the factors associated with the diagnostic performance of interferon-gamma release assay (IGRA) in HIV infected patients with active tuberculosis (TB). \u003c/p\u003e\u003cp\u003eMethods: We retrospectively analyzed the data of HIV infected patients with active tuberculosis patients from 2016-2019 who conformed with the inclusion criteria and the exclusion criteria. All patients included were performed with TB-IGRA. For evaluating the diagnostic performance of TB-IGRA, patients were divided into positive TB-IGRA and negative TB-IGRA groups. And all statistical analysis was performed using SPSS \u003c/p\u003e\u003cp\u003eResults: Performed by logistic regression analysis, we found that CD4 cell counts is independent risk factor for false negative of TB-IGRA(P\u0026lt;0.001). Additionally, false negative of TB-IGRA were 68.75%, 24.29% and 14.63%, respectively, in the three groups whose CD4+ T cell counts were \u0026lt;20/μL, 20-100/μL and \u0026gt;100/μL, with the highest frequency in subjects with CD4+ T cell counts \u0026lt;20/μL(P\u0026lt;0.001). And false negative of TB-IGRA were 68.75%, 27.77%, 20.58% and 14.63%, respectively, in the four groups \u0026lt;20/μL (n = 32), 20-50/μL (n = 36) ,51-100/μL (n = 34) and \u0026gt;100/μL (n = 82). The group of CD4+ T cell counts \u0026lt;20/μL had the highest false negative (P\u0026lt;0.001). There was no significant difference in the groups of 20-50/μL, 51-100/μL and \u0026gt;100/μL (P=0.483, P=0.623, respectively).\u003c/p\u003e\u003cp\u003e Conclusion: The low level of CD4+ T-cell counts increase false negative TB-IGRA in HIV infected patients with active tuberculosis. These data suggest IGRA assays may have unreliable diagnostic performance results among patients with advanced HIV especially CD4+ T cell counts were \u0026lt;20/μL.\u003c/p\u003e","manuscriptTitle":"The diagnostic performance of TB-IGRA on HIV infected patients with active tuberculosis is associated with CD4+ T-cell counts","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2019-10-21 22:37:08","doi":"10.21203/rs.2.16261/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"16eff64b-5a24-4176-87de-9fbfb4489f93","owner":[],"postedDate":"October 21st, 2019","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32803,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"","versionOfRecord":[],"versionCreatedAt":"2019-10-21 22:37:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6907","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-6907","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}