Background:
In high-burden settings, case fatality rates are reported to be between 11% and 32% in hospitalized patients with HIV-associated tuberculosis, yet the underlying causes of mortality remain poorly characterized. Understanding these causes could inform the development of novel management strategies to improve survival. We aimed to assess clinical, microbiologic, and immunologic determinants of mortality in this vulnerable population.
Abstract:
Methods: This prospective cohort study enrolled adults with HIV hospitalized with a new diagnosis of HIV-associated tuberculosis in Cape Town, South Africa, between 2014 and 2016. We assessed biomarkers of tuberculosis dissemination (urine LAM, urine Xpert MTB/RIF, and blood culture) and measured 28 host soluble inflammatory mediators at baseline.
Results: Of 576 participants with TB (84.5% microbiologically confirmed), 124 (21.5%) died within 12 weeks. Determinants of mortality included disseminated tuberculosis (79.6% of deaths versus 60.7% of survivors), sepsis syndrome (high lactate), and rifampicin-resistant TB (16.9% of deaths versus 7.2% of survivors). Immunologic profiling revealed a signature dominated by mediators of the innate immune system and chemotactic signaling (e.g., IL-1Ra, IL-6, IL-8, IP-10), which was strongly associated with mortality (aHR = 2.2) and TB dissemination.
Conclusion: Disseminated tuberculosis, sepsis syndrome, and drug resistance are major drivers of mortality in hospitalized HIV-TB patients. The associated hyper-inflammatory innate immune profile provides insights into the pathophysiology of death and identifies potential targets for host-directed therapies.
Keywords: HIV-associated tuberculosis; mortality; disseminated tuberculosis; inflammatory mediators; biomarkers.
Clique aqui
- Data de Publicação: 05/07/2019
- Autores: Charlotte SchutzID1,2*, David Barr3 , Bruno B. AndradeID1,4,5,6,7, Muki SheyID1,2, Amy WardID1,2, Saskia Janssen8 , Rosie BurtonID9 , Katalin A. WilkinsonID1,2,10, Bianca SossenID1,2, Kiyoshi F. Fukutani4,5,11, Mark NicolID12, Gary Maartens13, Robert J. WilkinsonID1,2,10,14, Graeme MeintjesID1,2
