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Management of active tuberculosis in adults with HIV.

ABSTRACT: Every year, about 1 million people living with HIV worldwide develop tuberculosis. Although the drug regimens used to treat tuberculosis in these patients are the same as those used in HIV-negative patients, cotreatment of tuberculosis with antiretroviral therapy involves challenges including the optimal timing of antiretroviral initiation, drug-drug interactions, drug tolerability, and the prevention and treatment of tuberculosis-associated immune reconstitution syndrome. Furthermore, mortality is high in people with HIV who are diagnosed with tuberculosis during a hospital admission, and in those with tuberculous meningitis. Studies in this field have better characterised these challenges and informed optimal management and guideline revisions. In patients with tuberculosis, antiretroviral therapy improves survival, is well tolerated, and can be adjusted to manage drug-drug interactions with rifampicin. Prednisone is effective in both preventing and treating the paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome.

SUBMITTER: Meintjes G

PROVIDER: S-EPMC6750245 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Management of active tuberculosis in adults with HIV.

Meintjes Graeme G Brust James C M JCM Nuttall James J Maartens Gary G

The lancet. HIV 20190701 7

Every year, about 1 million people living with HIV worldwide develop tuberculosis. Although the drug regimens used to treat tuberculosis in these patients are the same as those used in HIV-negative patients, cotreatment of tuberculosis with antiretroviral therapy involves challenges including the optimal timing of antiretroviral initiation, drug-drug interactions, drug tolerability, and the prevention and treatment of tuberculosis-associated immune reconstitution syndrome. Furthermore, mortality ...[more]

PMID: 31272663

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Project description:We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB).A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients' PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo.In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6-15.1) vs 3.6(3.6-3.6) pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001), severity-score (rs +0.317, P = 0.004), and fever and hospitalization durations (rs +0.407, P<0.001). IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02-1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08-1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2-2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034). Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-?) when combined with lipoarabinomannan.In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important roles in pathogenesis and disease manifestations. Our clinico-immunological data can provide basis for the development of new strategies for disease monitoring, management and control.

Dataset Information

Management of active tuberculosis in adults with HIV.

Publications

Management of active tuberculosis in adults with HIV.

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