Performance of Xpert MTB/RIF Ultra for the Diagnosis of Pulmonary Tuberculosis Using Bronchoalveolar Lavage Samples in People Living with HIV/AIDS (PLWHA) in China: A Prospective Study

Peize Zhang,1,&ast; HouMing Liu,2,&ast; Hui Wang,3,&ast; Yanbo Wu,4 Liqin Sun,3 Man Rao,3 Xinyun Jia,3 Ying Song,3 Guofang Deng,1 Tianpin Li,2 Feidi Ye,2 Yang Zhou,3 Yi Liao5 1Department of Lung Disease, The Third People’s Hospital of Shenzhen, Shenzhen City, Guangdong Province, People’s Republic of China; 2Department of Clinical Laboratory, The Third People’s Hospital of Shenzhen, Shenzhen City, Guangdong Province, People’s Republic of China; 3Department of Infectious Disease No.1, The Third People’s Hospital of Shenzhen, Shenzhen City, Guangdong Province, People’s Republic of China; 4Department of Infectious Disease, Shenzhen Longhua New District Central Hospital, Shenzhen City, Guangdong Province, People’s Republic of China; 5Department of Primary Health Promotion, Shenzhen Center for Disease Control and Prevention, Shenzhen City, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Zhou; Yi Liao Email yangzhou@szsy.sustech.edu.cn; ly_jht@126.comBackground: Sputum is commonly used for the diagnostic testing of pulmonary tuberculosis (PTB), but people living with HIV/AIDS (PLWHA) usually have little sputum. Moreover, the automated molecular test, Xpert MTB/RIF assay (Xpert), has a low sensitivity in PLWHA. We aimed to estimate the performance of Xpert Ultra on the detection of Mycobacterium tuberculosis (MTB) using bronchoalveolar lavage (BAL).Methods: From February 5, 2018 to March 30, 2019, a total of 99 PLWHA with suspected PTB at the Third People’s Hospital of Shenzhen, China, were recruited. The information on demographics and medical history, blood MTB antigen-specific interferon gamma enzyme-linked immunospot assay (T-SPOT.TB), T lymphocyte subsets, and plasma HIV RNA load were collected. Computed tomography (CT) and flexible bronchoscopy were performed, and BAL and blood samples were collected. Testing of acid-fast bacilli (AFB), tuberculosis real-time fluorescence quantitative PCR (TBDNA), Ultra, Xpert, and MTB culture were conducted.Results: Compared to BAL MTB culture for tuberculosis diagnosis, Ultra, Xpert, T-SPOT.TB, TBDNA and AFB smear had the sensitivity of 0.96 (24/25), 0.80 (20/25), 0.84 (21/25), 0.44 (11/25), and 0.12 (3/25), respectively; and the specificity of 0.92 (68/74), 0.96 (71/74), 0.93 (69/74), 0.96 (71/74), and 0.99 (73/74), respectively. Our study found that the sensitivity of Ultra was higher than that of culture and Xpert (AUC 0.92, 0.86 and 0.84, respectively). The results also indicated that PLWHA with CD4 < 200 cells/mm3 had reduced both sensitivity (from 1.00 and 0.86 to 0.94 and 0.78, respectively) and specificity (from 0.96 and 1.00 to 0.90 and 0.41, respectively) of Ultra and Xpert for the diagnosis of PTB.Discussion: Our data supported an increased sensitivity of Ultra compared to that of Xpert on BAL samples of PLWHA, regardless of the CD4 counts and reference diagnosis standards.Keywords: diagnosis of pulmonary tuberculosis, Xpert MTB/RIF Ultra, HIV-TB co-infection