Dataset Information

Matrix Metalloproteinases in Tuberculosis-Immune Reconstitution Inflammatory Syndrome and Impaired Lung Function Among Advanced HIV/TB Co-infected Patients Initiating Antiretroviral Therapy.

ABSTRACT:

Background

HIV-infected patients with pulmonary TB (pTB) can have worsening of respiratory symptoms as part of TB-immune reconstitution inflammatory syndrome (TB-IRIS) following antiretroviral therapy (ART) initiation. Thus, reconstitution of immune function on ART could drive incident lung damage in HIV/TB.

Methods

We hypothesized that increases in matrix metalloproteinases (MMPs), which can degrade lung matrix, on ART are associated with TB-IRIS among a cohort of advanced, ART naïve, HIV-infected adults with pTB. Furthermore, we related early changes in immune measures and MMPs on ART to lung function in an exploratory subset of patients post-TB cure. This study was nested within a prospective cohort study. Rank sum and chi-square tests, Spearman's correlation coefficient, and logistic regression were used for analyses.

Results

Increases in MMP-8 following ART initiation were independently associated with TB-IRIS (p = 0.04; adjusted odds ratio 1.5 [95% confidence interval: 1.0-2.1]; n = 32). Increases in CD4 counts and MMP-8 on ART were also associated with reduced forced expiratory volume in one-second post-TB treatment completion (r = - 0.7, p = 0.006 and r = - 0.6, p = 0.02, respectively; n = 14).

Conclusions

ART-induced MMP increases are associated with TB-IRIS and may affect lung function post-TB cure. End-organ damage due to TB-IRIS and mechanisms whereby immune restoration impairs lung function in pTB deserve further investigation.

SUBMITTER: Ravimohan S

PROVIDER: S-EPMC4793443 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

Matrix Metalloproteinases in Tuberculosis-Immune Reconstitution Inflammatory Syndrome and Impaired Lung Function Among Advanced HIV/TB Co-infected Patients Initiating Antiretroviral Therapy.

Ravimohan Shruthi S Tamuhla Neo N Kung Shiang-Ju SJ Nfanyana Kebatshabile K Steenhoff Andrew P AP Gross Robert R Weissman Drew D Bisson Gregory P GP

EBioMedicine 20151125

<h4>Background</h4>HIV-infected patients with pulmonary TB (pTB) can have worsening of respiratory symptoms as part of TB-immune reconstitution inflammatory syndrome (TB-IRIS) following antiretroviral therapy (ART) initiation. Thus, reconstitution of immune function on ART could drive incident lung damage in HIV/TB.<h4>Methods</h4>We hypothesized that increases in matrix metalloproteinases (MMPs), which can degrade lung matrix, on ART are associated with TB-IRIS among a cohort of advanced, ART n ...[more]

PMID: 27014741

Similar Datasets

Project description:Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution.This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-? upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits.Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-? production in response to PPD antigen were CD4+ T cell counts <200 cells/mm3 at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4+ T cell counts. Moreover, the factors associated with the production of IFN-? in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4+ T cell counts at follow-up visits of ?200 cells/mm3.These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-? production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude compared to ESAT-6 and are associated with different factors. The low response to ESAT-6, even during immune restoration, suggests that this antigen is not adequate to assess the immune response of immunosuppressed TB-HIV patients.

Dataset Information

Matrix Metalloproteinases in Tuberculosis-Immune Reconstitution Inflammatory Syndrome and Impaired Lung Function Among Advanced HIV/TB Co-infected Patients Initiating Antiretroviral Therapy.

Background

Methods

Results

Conclusions

Publications

Matrix Metalloproteinases in Tuberculosis-Immune Reconstitution Inflammatory Syndrome and Impaired Lung Function Among Advanced HIV/TB Co-infected Patients Initiating Antiretroviral Therapy.

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