Delayed diagnosis of tuberculosis in persons living with HIV in Eastern Europe: associated factors and effect on mortality—a multicentre prospective cohort study
Authors: Kraef Christian , Bentzon Adrian , Panteleev Alexander , Skrahina Alena , Bolokadze Natalie , Tetradov Simona , Podlasin Regina , Karpov Igor , Borodulina Elena , Denisova Elena , Azina Inga , Lundgren Jens , Johansen Isik Somuncu , Mocroft Amanda , Podlekareva Daria , Kirk Ole ,   for the T. B.:H. I. V. Study Group, Vassilenko A. , Klimuk D. , Kondratenko O. , Zalutskaya A. , Bondarenko V. , Mitsura V. , Kozorez E. , Tumash O. , Suetnov O. , Paduto D. , Iljina V. , Kummik T. , Mshvidobadze K. , Lanchava N. , Goginashvili L. , Mikiashvili L. , Bablishvili N. , Rozentale B. , Zeltina I. , Janushkevich I. , Caplinskiene I. , Caplinskas S. , Kancauskiene Z. , Wiercinska-Drapalo A. , Thompson M. , Kozlowska J. , Grezesczuk A. , Bura M. , Knysz B. , Inglot M. , Garlicki A. , Loster J. , uiculescu D. D , Rakhmanova A. , Panteleev O. , Yakovlev A. , Kozlov A. , Tyukalova A. , Vlasova Y. , rofimov T. T. , Kyselyova G. , Obel N. , Gerstoft J. , Kronborg G. , Payen M. C. , abeya K. K , Necsoi C. , Dabis F. , Tsaranazy A. , Cazanave C. , Furrer H. , Sagette M. , Rickenbach M. , Sculier D. , Calmy A. , Cavassini M. , Bruno A. , Bernasconi E. , Hoffmann M. , Vernazza P. , Fehr J. , Weber R. , Miller R. , Vora N. , Cooke G. , Mullaney S. , Wilkins E. , George V. , Collini P. , Dockrell D. , Post F. , Campbell L. , Brum R. , Mabonga E. , Saigal P. , Kegg S. , Ainsworth J. , Waters A. , Dhar J. , Ellis K. , Girardi E. , Rianda A. , Galati V. , Pinnetti C. , Tommasi C. , Lapadula G. , Di Biagio A. , Parisini A. , Carbonara S. , Angarano G. , Purgatorio M. , Matteelli A. , Apostoli A. , Miro J. M. , Manzardo C. , Ligero C. , Gonzalez J. , Martinez-Martinez Jose A. , Sanchez F. , Knobel H. , Salvadó M. , Lopez-Colomes J. L. , Martínez-Lacasa X. , Cuchí E. , Falcó V. , Curran A. , Tortola M. T. , Ocaña I. , Vidal R. , Sambeat M. A. , Pomar V. , Coll P. , Pozamczer D. , Saumoy M. , Alcaide F. , Caylà J. , Moreno A. , Millet J. P. , Orcau A. , Fina L. , Romero A. , Roldan L. L. , Iribarren J. A. , Ibarguren M. , Moreno S. , González A. , Miralles P. , Aldámiz-Echevarría T. , Losso M. , Toibaro J. , Gambardella L. , Toibaro J. , Moreno Macias L. , Warley E. , Tavella S. , Garcia Messina O. , Gear O. , Laplume H. , Marson C. , Contarelia J. , Michaan M. , Scapellato P. , Bartoletti B. , Palmero D. , Elias C. , Cortes C. , Crabtree B. , Mosqueda Gomez J. L. , Villanueva J. A. , Gonzalez Hernandez L. A. , Badial F. 
Published: October 2021

Abstract
Background
Early diagnosis of tuberculosis (TB) is important to reduce transmission, morbidity and mortality in people living with HIV (PLWH).

Methods
PLWH with a diagnosis of TB were enrolled from HIV and TB clinics in Eastern Europe and followed until 24 months. Delayed diagnosis was defined as duration of TB symptoms (cough, weight-loss or fever) for ≥ 1 month before TB diagnosis. Risk factors for delayed TB diagnosis were assessed using multivariable logistic regression. The effect of delayed diagnosis on mortality was assessed using Kaplan–Meier estimates and Cox models.

Findings
480/740 patients (64.9%; 95% CI 61.3–68.3%) experienced a delayed diagnosis. Age ≥ 50 years (vs. < 50 years, aOR = 2.51; 1.18–5.32; p = 0.016), injecting drug use (IDU) (vs. non-IDU aOR = 1.66; 1.21–2.29; p = 0.002), being ART naïve (aOR = 1.77; 1.24–2.54; p = 0.002), disseminated TB (vs. pulmonary TB, aOR = 1.56, 1.10–2.19, p = 0.012), and presenting with weight loss (vs. no weight loss, aOR = 1.63; 1.18–2.24; p = 0.003) were associated with delayed diagnosis. PLWH with a delayed diagnosis were at 36% increased risk of death (hazard ratio = 1.36; 1.04–1.77; p = 0.023, adjusted hazard ratio 1.27; 0.95–1.70; p = 0.103).

Conclusion
Nearly two thirds of PLWH with TB in Eastern Europe had a delayed TB diagnosis, in particular those of older age, people who inject drugs, ART naïve, with disseminated disease, and presenting with weight loss. Patients with delayed TB diagnosis were subsequently at higher risk of death in unadjusted analysis. There is a need for optimisation of the current TB diagnostic cascade and HIV care in PLWH in Eastern Europe.