CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

715 DIAGNOSIS OF LATENT TUBERCULOSIS AMONG US-BORN PEOPLE LIVING WITH HIV April Pettit 1 , Jason Stout 2 , Robert Belknap 3 , Constance A. Benson 4 , Marie Nancy Seraphin 5 , Michael Lauzardo 5 , David Horne 6 , Richard S. Garfein 4 , Fernanda Maruri 1 , Dolly Katz 7 , Christine Ho 7 , for the Tuberculosis Epidemiologic Studies Consortium (TBESC) 1 Vanderbilt University, Nashville, TN, USA, 2 Duke University, Durham, NC, USA, 3 Denver Health and Hospital Authority, Denver, CO, USA, 4 University of California San Diego, San Diego, CA, USA, 5 University of Florida College of Medicine, Gainesville, FL, USA, 6 University of Washington, Seattle, WA, USA, 7 CDC, Atlanta, GA, USA Background: Persons living with HIV (PLWH) are a priority for latent tuberculosis infection (LTBI) screening due to the risk of progression to active tuberculosis (TB). Studies of LTBI diagnostic test characteristics are conflicting and limited by the lack of a gold standard. Methods: The TB Epidemiologic Studies Consortium is conducting a multicenter prospective cohort study to evaluate the performance of the tuberculin skin test (TST), QuantiFERON Gold In-Tube (QFT) and T-SPOT.TB (TSPOT). We analyzed US-born PLWH >5 years old who had valid results for all three tests and were enrolled from 18 clinics during September 2012- April 2017. We estimated LTBI prevalence and test characteristics, using Bayesian latent class analysis models with varying cutpoints. Sensitivity and specificity were used to quantify the under- and overdiagnosis of LTBI per 1000 persons screened with varying LTBI prevalence. Results: Among 1510 participants, median age was 49 years (interquartile range [IQR] 42-55), 1073 (71%) were male, 1057 (70%) were black; 945 (62.6%) had a self-reported CD4+ count (median 532 cells/mm3, IQR 355-764). LTBI prevalence was estimated at 5.1% (95% credible interval [95Crl] 3.4 to 7.0%) overall (range 0.8-14.5% by site). Table 1 describes test characteristics. Using the standard US cutpoints, the QFT had higher sensitivity (Sn) than the TST (difference [diff] 16.0%, 95Crl 2.3 to 30) and TSPOT (diff 15.4%, 95Crl 0 to 30.8%). The difference in the Sn was 0.6% (95Crl -12.6 to 14.6) for the TSPOT compared to TST. The TSPOT had higher specificity (Sp) than the TST (diff 2.6%, 95Crl 1.6 to 3.8) and QFT (diff 2.9%, 95Crl 1.7 to 4.2). The difference in the Sp was 0.3% (95Crl -1.2 to 1.7) for the TST compared to QFT. The difference in positive predictive value (PPV) was 4.2% (95Crl -9.0 to 17.8) for the QFT compared to TST; TSPOT had higher PPV than TST (diff 37.1%, 95Crl 20.8 to 52.3) and QFT (diff 32.9%, 95Crl 15.4 to 49.2%). Conclusion: Using the standard US cutpoints and 5% LTBI prevalence, Sn was highest for QFT; Sp and PPV were highest for TSPOT. Both the international (>6 spots) and US (>8 spots) TSPOT cutoffs resulted in more LTBI under- than overdiagnosis, regardless of LTBI prevalence. For the TST and the QFT, the US cutoffs (5mm for TST and 0.35 IU/mL for QFT) resulted in more LTBI over- than underdiagnosis in a population with medium LTBI prevalence (5.1%); however, the optimal cutoff of the TST and QFT varied depending on LTBI prevalence.

716 QUANTIFICATION OF CD64: A PREDICTIVE BIOMARKER FOR PROGRESSION TO ACTIVE TUBERCULOSIS

Cristina Ceriani , Arianna Gatti, Massimo Villa, Maria Teresa Manco, Massimo De Paschale, Ilaria Caramma, Bruno Brando, Pierangelo Clerici ASST Ovest Milanese, Legnano, Italy Background: To reach the goal of end-Tuberculosis strategy, new biomarkers are needed to identify active tuberculosis (TB). Currently, only QuantiFERON® TB assay (QTF) is used in peripheral blood for screening tuberculosis infection. However, this method cannot distinguish active from latent TB infection (LTBI). Recent studies show a transcriptional increase of several genes, including CD64, which code for a high affinity Fc receptor I involved in inflammatory reactions. In addition, Neutrophils (NE) and Monocytes (MO) exert bactericidal responses by producing inflammatory proteins caused by infection with M. Tuberculosis (MBT). The purpose of this study was to quantify CD64 expression on the surface of NE and MO as a predictive biomarker of progression from LTBI to active TB in QuantiFERON® (QTF) positive or indeterminate patients Methods: Patients were enrolled with positive and indeterminate QTF. Non- systemic infections were documented. Flow cytometric quantitative expression of CD64 was evaluated from peripheral blood samples and expressed in ABC (Antibody Binding Capacity) units, with NE normal range <1000 ABC and MO normal range 15000-20000 ABC. MTB cultures from respiratory specimens were also performed. Results: Of the 45 positive QTF cases, 25 MTB cultures were positive and 16 were negative. The positive QTF with negative MTB cultures were considered LTBI. The median of NE CD64 ABC and MO CD64 ABC was significantly higher (p<0.001) in MTB positive cultures (NE 3593 ABC; MO 38757 ABC) than in MTB negative cultures (NE 724 ABC; MO 17151 ABC) (Fig. a). The NE CD64 and MO CD64 AUC-ROC values were 0.948 (95% CI 0.838-0.992) and 0.989 (0.901-1.000), respectively (Fig. b). By establishing the NE CD64 value of >2400 ABC or the MO CD64 value of >25800, the sensitivity increased to 95.5% (82.2-99.9) with 100% specificity and 100% Positive Predictive Values (PPVs) (Fig. c). Of the 6 indeterminate QTF enrolled, the 4 with MTB positive cultures showed NE CD64 >2400 ABC or MO CD64 value >25800 ABC and the 2 with MTB negative cultures showed NE CD64 <1000 ABC or MO CD64 <23000 ABC. Conclusion: The quantification of NE and MO CD64 expression is a powerful diagnostic tool in discriminating between active TB and LTBI and may be used as predictive biomarker of active TB in patients with a positive QTF test. Providing a fast diagnostic solution, this may address the limitation of current tuberculosis diagnostics. Further studies with a larger patient cohort are needed to validate our preliminary data.

Poster Abstracts

CROI 2019 275