Novel tuberculosis (TB) prevention and control strategies are urgently required. Utilising specimens from the Improving Retreatment Success (NCT02114684) trial we assessed the associations between inflammatory markers, measured during active TB, with treatment response and disease severity in HIV-infected and uninfected individuals. Multiplex immunoassays and ELISA were used to measure plasma expression of 24 cytokines/chemokines.
View Article and Find Full Text PDFThere is an urgent need to identify immunological markers of tuberculosis (TB) risk in HIV co-infected individuals. Previously we have shown that TB recurrence in HIV co-infected individuals on ART was associated with markers of systemic inflammation (IL-6, IL1β and IL-1Rα). Here we examined the effect of additional acute inflammation and microbial translocation marker expression on risk of TB recurrence.
View Article and Find Full Text PDFClin Infect Dis
June 2020
Background: New onset or worsening drug-induced liver injury challenges coinfected patients on antiretroviral therapy (ART) initiation during antituberculosis (TB) treatment.
Methods: Post hoc analysis within a randomized trial, the Starting Antiretroviral Therapy at Three Points in Tuberculosis trial, was conducted. Patients were randomized to initiate ART either early or late during TB treatment or after TB treatment completion.
Front Microbiol
June 2019
HIV-infected individuals are at high risk of tuberculosis disease and those with prior tuberculosis episodes are at even higher risk of disease recurrence. A non-sputum biomarker that identifies individuals at highest tuberculosis risk would allow targeted microbiological testing and appropriate treatment and also guide need for prolonged therapy. We determined the utility of a previously developed whole blood transcriptomic correlate of risk (COR) signature for (1) predicting incident recurrent tuberculosis, (2) tuberculosis diagnosis and (3) its potential utility for tuberculosis treatment monitoring in HIV-infected individuals.
View Article and Find Full Text PDFBackground: The substitution of moxifloxacin for ethambutol produced promising results for improved tuberculosis treatment outcomes.
Methods: We conducted an open-label, randomized trial to test whether a moxifloxacin-containing treatment regimen was superior to the standard regimen for the treatment of recurrent tuberculosis. The primary and secondary outcomes were the sputum culture conversion rate at the end of 8 weeks and the proportion of participants with a favorable outcome, respectively.
Infect Drug Resist
September 2018
Background: Recurrent tuberculosis (TB) following TB treatment completion in HIV-infected individuals remains a major public health burden. We assessed the role of various risk factors in mediating the development of recurrent TB and subsequent resistance to antiretroviral therapy and anti-TB drugs.
Patients And Methods: We analyzed secondary demographic, clinical, and laboratory data from medical records of five HIV-infected TB patients enrolled between 2009 and 2014 in a prospective observational study investigating TB recurrence.
In attaining UNAIDS targets of 90-90-90 to achieve epidemic control, understanding who the current utilizers of HIV treatment services are will inform efforts aimed at reaching those not being reached. A retrospective chart review of CAPRISA AIDS Treatment Program (CAT) patients between 2004 and 2013 was undertaken. Of the 4043 HIV-infected patients initiated on ART, 2586 (64.
View Article and Find Full Text PDFMono-antennary galacto derivatives of cholesterol are being actively developed to direct lipoplexes to the asialoglycoprotein receptor (ASGP-R) on hepatocytes. Here we report on a novel ASGP-R ligand cholest-5-en-3-yl [1-(β-D-galactopyranosyl)-1H-1,2,3-triazol-4-yl]methylcarbamate (4), assembled by a copper(I)-catalyzed azide-alkyne cycloaddition (click chemistry), and compare it with cholest-5-en-3-yl-β-D-galactopyranoside (2) and cholest-5-en-3-yl [1-(β-D-galactopyranosyl-1'-oxy)phen-4-yl]carbamate (3), in liposome formulations with or without 5 mol% distearoylphosphatidylethanolamine poly(ethylene glycol)2000, intended for DNA delivery to ASGP-R-positive hepatocyte-derived HepG2 cells and the ASGP-R-negative embryo kidney cell line HEK293. Transfection levels attained with lipoplex 4 were 100 and 300% greater than those for lipoplexes 2 and 3 respectively in HepG2 cells, while competition assays reduced transfection levels by up to 98%.
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