High Performance of Systematic Combined Urine Liboarabinomannan Test and Sputum Xpert MTB/RIF for Tuberculosis Screening in Severely Immunosuppressed Ambulatory Adults With Human Immunodeficiency Virus
Authors: Bonnet Maryline , Gabillard Delphine , Domoua Serge , Muzoora Conrad , Messou Eugène , Sovannarith Samreth , Nguyen Duc Bang , Badje Anani , Juchet Sylvain , Bunnet Dim , Borand Laurence , Natukunda Naome , Tran Thị Hong , Anglaret Xavier , Laureillard Didier , Blanc François-Xavier ,   for the Systematic empirical vs. Test-guided Anti-tuberculosis Treatment Impact in Severely immunosuppressed HIV-infected adults initiating antiretroviral therapy with CD4 cell counts &lt;100/mm3 (STATIS) Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) 12290 Trial Team, Aka Kakou , Aoussi Eba , Bissagnene Emmanuel , Eholié Serge , Ello Frédéric , Nzunetu Gustave , Rabe Cyprien , Sidibé Baba , Adjé Florence , Ahonou Boris , Amani Jacqueline , Anzian Amani , Assoua Anicet , Ayemou Lucien , Diomandé Glao , Etilé Etienne , Gnokoro Joachim , Goli Jeannot , Gouesse Patrice , Kati-Coulibaly Loukou , Konan Lambert , Konan Edwige , Kouadio Francis , Kouakou Martial , Kouamé Aristide , Labibi Georgette , Lathro Marie Cécile , Nogbout Marie-Pascale , N’Dry Lucie , Tchehy Amah , Zadi Ida , Ahiboh Hugues , Emieme Arlette , Inwoley André , Kabran Mathieu , Menan Hervé , Ouassa Timothée , Toni Thomas-d’Aquin , N’Guessan Raymond , Aboua Adrienne , Ahyi Irmine , Cissé Adoulaye , Danel Christine , Konan Allé Baba DiengRomuald , N’Chot Célestin , Koffi Larissa N’Guessan , Konan Sylvie , Kouadio Suzanne , Menan Gérard , Moh Raoul , Siloué Bertine , Yao-Yapi Cyril , Aheisibwe Hillary , Arinaitwe Rinah , Atuhaire Syson , Kesande Claire , Isaac Isaac Ampaire , Kajabwangu Rodgers , Kyasiimire Stella , Kyarimpa Rose , Mpeirwe Doreen , Mugabirwe Gaudioza , Nansumba Margret , Natukunda Eva , Namubiru Teddy , Nakanwagi Masturah , Nkeramahame Junenal , Nyangoma Miria , Tayebwa Colman , Orikiriza Patrick , Mugisha Ivan Taremwa , Turyashemererwa Esther , Nanjebe Deborah , Turuho Thadeous , Nalusaji Aisha , Ayabare Arnold , Kabanda Ronald , Kassaza Kennedy , Muwanga and Sulaiman , Mean Chi Vun , Ly Penh Sun , Chea Daly , Mom Chandara , Pich Sophana , Sar Sandap , Bun Vannary , Chan Kuong , Chhneang Virin , Chhum Chheng Kong , Khiev Samnang , Sreng Setha Lim , Long Nary , Ly Makara , Ma Suon Sopheak , Mao Kimcolin , Men Panharoat , Mol Sovannary , Nhem Vandoeun , Nin Navy , Roeun Moeung , So Manith , Sok Phal , Song Sovannara , Sos Mary , Sotheara  , Thim  , Uk Narith , Um Sokha , Mao Tan Eang , Yanith Che , Chim Socheat , Chum Bun Than , Dara Doung , Din Chanthy , Eng Panha , Hang Putheary , Im Savorn , Keath Huy , Keo Karona , Khem Sok Lida , Lay Phirum , Leng Phalla , Oeung Chiv Hun , Ouk Kalyan , Pe Reaksmey , Phe Thong , Phoung Bunthy , Rouen Mono , San Sok Leang , Sek Sophy , Sina Teav , Srey Pichsovannary , Sun Seakly , Thai Sopheak , Veng Chhun Heng , Suntouch Young , Cheng Sokleaph , Heng Seiha , Kerléguer Alexandra , Hek Morina , Him Brembrey , Keo Monorea , Nang Boraneath , Suom Sophea , Thaan Sreymom , City Ho Chi Minh , Dang Le Minh Tri , Lam Quoc Dung , Le Hong Ngoc , Nguyen Thi Hieu , Nguyen Thi Hong , Nguyen Huu Minh , Nguyen Van Song , Nguyen Ha Uyen , Nguyen Nhu Viet , Nguyen Thi Bich Yen , Pham Thi Tuong Vy , Tran Ngoc Thach , Tran Pham Phuong Thao , To My Huong , Nguyen Huu Lân , Anh Thi Quynh , Nguyen  , Pham Hung Cuong , Nguyen Thi Thuy Nga , Quach Kim Ung , Tieu Thi Thu Van , Nguyen Ngoc Lan , Nguyen Thi Cao Van , Tran Huu Loc , Vu Xuan Thinh , Huynh Khanh Thu , Luong Que Anh , Truong Thi Xuan Lien , Dinh Thi Thanh , Domergue Anaïs , Guiroy Frédérique , Le Quoc Khanh , Rapoud Delphine , Tran Thi Hai Ly , Carrou Jérôme Le , Karcher Sophie , Clouet Gwenaëlle , Lawn Stephen D 
Published: March 2023

Abstract

Background
In people with human immunodeficiency virus (PWH), the World Health Organization–recommended tuberculosis (TB) 4-symptom screen (W4SS) targeting those who need molecular rapid testing may be suboptimal. We assessed the performance of different TB screening approaches in severely immunosuppressed PWH enrolled in the guided-treatment group of the STATIS trial (NCT02057796).

Methods
Ambulatory PWH with no overt evidence of TB and CD4 count &lt;100 cells/µL were screened for TB prior to antiretroviral therapy (ART) initiation with W4SS, chest radiograph (CXR), urine lipoarabinomannan (LAM) test, and sputum Xpert MTB/RIF (Xpert). Correctly and wrongly identified cases by screening approaches were assessed overall and by CD4 count threshold (≤50 and 51–99 cells/µL).

Results
Of 525 enrolled participants (median CD4 count, 28 cells/µL), 48 (9.9%) were diagnosed with TB at enrollment. Among participants with a negative W4SS, 16% had either a positive Xpert, a CXR suggestive of TB, or a positive urine LAM test. The combination of sputum Xpert and urine LAM test was associated with the highest proportion of participants correctly identified as TB (95.8%) and non-TB cases (95.4%), with proportions equally high among participants with CD4 counts above or below 50 cells/µL. Restricting the use of sputum Xpert, urine LAM test, or CXR to participants with a positive W4SS reduced the proportion of wrongly and correctly identified cases.

Conclusions
There is a clear benefit to perform both sputum Xpert and urine LAM tests as TB screening in all severely immunosuppressed PWH prior to ART initiation, not only in those with a positive W4SS.
Clinical Trials Registration. NCT02057796.