Dataset Information

Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients.

ABSTRACT: Despite the immune-reconstitution with antiretroviral therapy (ART), HIV-infected individuals remain highly susceptible to tuberculosis (TB) and have an enrichment of oral anaerobes in the lung. Products of bacterial anaerobic metabolism, like butyrate and other short-chain fatty acids (SCFAs), induce regulatory T cells (Tregs). We tested whether SCFAs contribute to poor TB control in a longitudinal cohort of ART-treated HIV-infected South Africans. Increase in serum SCFAs was associated with increased TB susceptibility. SCFAs inhibited IFN-? and IL-17A production in peripheral blood mononuclear cells from HIV-infected ART-treated individuals in response to M. tuberculosis antigen stimulation. Pulmonary SCFAs correlated with increased oral anaerobes, such as Prevotella in the lung, and with M. tuberculosis antigen-induced Tregs. Metabolites from anaerobic bacterial fermentation may, therefore, increase TB susceptibility by suppressing IFN-? and IL-17A production during the cellular immune response to M. tuberculosis.

SUBMITTER: Segal LN

PROVIDER: S-EPMC5465639 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients.

Segal Leopoldo N LN Clemente Jose C JC Li Yonghua Y Ruan Chunhai C Cao Jane J Danckers Mauricio M Morris Alison A Tapyrik Sarah S Wu Benjamin G BG Diaz Philip P Calligaro Gregory G Dawson Rodney R van Zyl-Smit Richard N RN Dheda Keertan K Rom William N WN Weiden Michael D MD

Cell host & microbe 20170330 4

Despite the immune-reconstitution with antiretroviral therapy (ART), HIV-infected individuals remain highly susceptible to tuberculosis (TB) and have an enrichment of oral anaerobes in the lung. Products of bacterial anaerobic metabolism, like butyrate and other short-chain fatty acids (SCFAs), induce regulatory T cells (Tregs). We tested whether SCFAs contribute to poor TB control in a longitudinal cohort of ART-treated HIV-infected South Africans. Increase in serum SCFAs was associated with in ...[more]

PMID: 28366509

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Project description:BackgroundWe aimed to determine the relationship between common pre-existing comorbidities in patients with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) with rates of all-cause mortality after TB treatment.MethodsWe conducted a retrospective cohort study among patients treated for rifampicin-resistant and multi/extensively drug resistant (RR and M/XDR) TB in the country of Georgia during 2009-2017. Eligible participants were >15 years of age with newly diagnosed, laboratory-confirmed drug resistant TB who received second-line treatment. Exposures included HIV serologic status, diabetes, and HCV status. The primary outcome was post-TB treatment mortality determined by cross-validating vital status with Georgia's national death registry through November 2019. We estimated hazard rate ratios (HR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without pre-existing comorbidities using cause-specific hazard regressions.ResultsAmong 1032 eligible patients included in our analyses, 34 (3.3%) participants died during treatment and 87 (8.7%) died post-TB treatment. Among those who died post-TB treatment, the median time to death was 21 months (IQR 7-39) after TB treatment ended. After adjusting for potential confounders, the hazard rates of mortality post-TB treatment were higher among participants with HIV co-infection (adjusted hazard ratio [aHR]=3.74, 95%CI 1.77-7.91) compared to those without HIV co-infection.ConclusionsIn our cohort, post-TB mortality occurred most commonly in the first three years after TB treatment ended. Additional post-TB care and follow-up, especially among patients with TB and comorbidities (especially HIV co-infection), may reduce rates of mortality post-TB treatment.SummaryOur findings provide evidence that TB patients with comorbidities, especially HIV, may have a significantly increased risk of post-TB mortality compared to those without comorbidities. We also found that most post-TB mortality occurred within three years after TB treatment completion.

Project description:BackgroundHIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis.MethodsWe did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection.FindingsWe included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death.InterpretationUse of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued.FundingAmerican Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Dataset Information

Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients.

Publications

Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients.

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