CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: NanoDisk-MS detection of a TB-specific CFP-10 peptide in sera revealed sensitivity and specificity for TB diagnosis in HEI and HEU infants and displayed results suggesting its potential for early TB detection and the monitoring of anti-TB treatment responses. 759 PROMISING COMBINED IMMUNOLOGICAL ASSAYS TO DIAGNOSE CHILDHOOD TUBERCULOSIS Edouard Tuaillon 1 , Mwiya Mwiya 2 , Laurent Kremer 1 , Melany w. Tonga 2 , Duncan Chanda 3 , Marianne Periès 1 , Amandine Pisoni 1 , Karine Bolloré 1 , Roselyne Vallo 1 , Chipepo Kankasa 2 , Philippe Van de Perre 1 , Jean-Pierre Molès 1 , Nicolas Nagot 1 1 INSERM, Montpellier, France, 2 University Teaching Hospital, Lusaka, Zambia, 3 Institute for Medical Research and Training, Lusaka, Zambia Background: Children account for a substantial part of the tuberculosis (TB) burden. However, the real burden of the disease is imprecise because the diagnosis of active tuberculosis remains a challenge in children. The development of non-sputum-based diagnostics assays and triage assays to rule-out TB are considered as especially critical to improve TB diagnosis in children. We aimed at constructing an algorithm aimed to improve the diagnostic of TB in children using a combination of immunoassays based on the T cells and serologic response against cytokine and Interferon-γ release assays. Methods: We designed an early proof-of-principle evaluation phase including children with confirmed TB and healthy controls in Zambia. The confirmed TB group consisted of children with positive clinical signs (prolonged cough, unexplained weight loss or fever, lethargy) and tested positive for MTB culture or GeneXpert® MTB/RIF assays. The control group consisted of healthy children without any clinical signs and no history of direct exposure to TB. Blood specimens were tested using the QuantiFERON Gold-IT®assay, (QFT®) and cytokines released in supernatants were quantified using a 25-plex cytokine multiplex test and ELISA assays. Serological response directed against Ag85A, B and D were tested by ELISA. A Random Forest classification analysis using values of all biomarkers was used in order to identify the most discriminant biological factors. Thresholds for each values were fixed with ROC curves. A simplified score was constructed out of these values. Results: The TB confirmed group consisted of 37 children with 51% being HIV coinfected, for the control group, 70 children were enrolled, 44% being HIV coinfected. We identified anti-Ag85B Abs, IL2/IFNg ratio, MIG and IP10 as the most sensitive biomarkers for TB diagnosis. Because MIG and IP10 responses were strongly correlated, we kept only MIG in further analysis. Using ROC curves and the Youden index, the threshold of 151 pg/mL, 0.76 and 48.6, discriminated best confirmed TB children from controls, for MIG, Ag85B Ab and IL2 Elisa/IFNg ratio respectively. According to our combined tests, a child was declared with TB if (i) IL2/IFNg <48.6 or (ii) both MIG (from QTF® supernatant) >151 pg/mL and Ag85B Ab > 0.76. The ROC curve derived from our score showed an AUC of 0.94 (0.90-0.99), giving 86% sensitivity and 87% specificity. Conclusion: The encouraging diagnostic performance of this score is the highest so far using immunological tests. In addition, the score is independent of the HIV status of the child. 760 WITHDRAWN 761LB ACCURACY OF NOVEL BLOOD ASSAY FOR IDENTIFICATION OF TB DISEASE IN PEOPLE WITH HIV Erik Södersten 1 , Anna Mantsoki 2 , Romain Wyss 2 , David Persing 1 , Sara Banderby 1 , Linda Strömqvist Meuzelaar 1 , Jacqueline Prieto 1 , Devasena Gnanashanmugam 1 , Purvesh Khatri 3 , Stefano Ongarello 2 , Samuel G. Schumacher 2 , Claudia Denkinger 4 1 Cepheid, Solna, Sweden, 2 FIND, Geneva, Switzerland, 3 Stanford University, Stanford, CA, USA, 4 Heidelberg University, Heidelberg, Germany Background: A non-sputum triage test to rule out tuberculosis disease has been identified as a high-priority need for diagnostic development to reach the End-TB targets of the World Health Organization (WHO). The target product profile defines a minimum of 90% sensitivity and 70% specificity for the test to be used by first-contact providers to identify patients who need further confirmatory testing. A combinatory score based on a novel 3-gene host- signature has shown promise in discriminating TB disease from other respiratory illnesses and healthy controls. Cepheid (Sunnyvale, CA, USA) has developed an early prototype GeneXpert PCR test (‘Xpert Prototype’), that quantifies relative mRNA-levels of the 3-gene signature in a patient whole blood sample.

AIDS Centre, Lviv, Ukraine, 6 All-Ukrainian network of people living with HIV/AIDS, Kyiv, Ukraine, 7 Hospital for Infectious Diseases, Warsaw, Poland Background: Tuberculosis (TB) remains the leading cause of death among HIV-infected adults in Ukraine. Urine lipoarabinomannan (LAM) antigen testing is a new rapid TB diagnostic that recently was implemented by Ukrainian National Public Health Center. We evaluated the utility of urine LAM in high TB prevalence and resource constrained settings. Methods: Between March-August 2019, 1770 consecutive HIV-infected patients presenting for routine follow-up visits had LAM testing performed in Kyiv (North), Odessa (South), Dnipro (East) and Lviv (West) regions of Ukraine. The inclusion criteria were: HIV+, ≥18, CD4 < 200 cells/mm 3 and/or clinically advanced HIV disease, regardless of TB symptoms. TB was confirmed by chest radiography, CT and/or bacteriological methods The project was funded by All-Ukrainian Network of People Living with HIV/AIDS. Results: In total 918 patients with both TB assessment and LAM performed were included in preliminary analyses. Mean age of participants was 41.0 years, 56.9%were male, and the mean baseline CD4 count was 157 cells/mm 3 .Of 586 confirmed TB cases, 400 (43,6%) had positive LAM test failed to detect 186 (26,3%) TB cases. TB prevalence in the sample was 63.83%. Sensitivity of LAM tests - 68.26%, Specificity – 87.35%. Positive predictive value - 90.5%. Negative predictive value – 60.92% (Table). Kappa statistics provided an estimate of moderate agreement (kappa 0.51,p-value <.0001, 95% CI=0.46, 0.56). Conclusion: LAM urine test is useful as an add-on rapid diagnostic method in Ukraine for HIV patients with a CD4 of <200. Sensitivity was satisfying, however for accurate and quick diagnosis LAM should be used in combination with other TB diagnostics 758 EVALUATION OF A BLOOD-BASED ANTIGEN TEST FOR TUBERCULOSIS IN INFANTS Liyan Mao 1 , Sylvia LaCourse 2 , Soyeon Kim 3 , Charles D. Mitchell 4 , Tony Hu 1 1 Tulane University, Metairie, LA, USA, 2 University of Washington, Seattle, WA, USA, 3 Harvard University, Cambridge, MA, USA, 4 University of Miami, Miami, FL, USA Background: Improved methods are urgently needed for pediatric tuberculosis (TB) diagnosis. We evaluated the performance of a blood-based assay (NanoDisk-MS), which utilizes immunoenrichment and mass spectrometry to quantify a TB-specific CFP-10 peptide, for TB diagnosis in HIV-exposed South African infants enrolled in an isoniazid TB prevention trial (IMPAACT P1041). Methods: Cryopreserved sera from 519 infants (284 HIV-exposed infected [HEI], 235 HIV-exposed uninfected [HEU]) were evaluated for CFP-10 peptide expression by NanoDisk-MS. At entry, all subjects were BCG-immunized, 90-120 days of age, and TB-disease-negative. They were randomized 1:1 to isoniazid or placebo and followed for up to 192 weeks for TB disease or infection. For this analysis, all children were classified as Confirmed, Unconfirmed or Unlikely TB cases using 2015 NIH TB diagnostic criteria and clinical, laboratory, histopathological, and radiological data. Results: NanoDisk-MS exhibited sensitivity for Confirmed (5/5, 100%; 95% CI: 47.8–100) and Unconfirmed (36/43, 83.7%; 69.3–93.2) TB cases in HEI, with 93.1% (203/218, 88.9–96.1) specificity. In the HEU group, NanoDisk-MS detected the single Confirmed TB case and most of the Unconfirmed TB cases (15/20, 75.0%; 50.9–91.3), and had 96.2% (177/184, 92.3–98.5) specificity. Most (72.7%) CFP-10-positive subjects with Unlikely TB diagnoses also exhibited at least one criterion for TB diagnosis (11/15; 73.3% HEI and 5/7; 71.4% HEU). For TB cases, CFP-10 peptide could be detected in serum drawn ≤ 60 weeks before TB diagnosis, and its diagnostic sensitivity reached 83.3% (5/6, 35.9–99.6) at ≤ 12 weeks before diagnosis. CFP-10 peptide positivity and expression levels declined following anti-TB therapy initiation.

Poster Abstracts

CROI 2020 280