title: 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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Botswana-UPenn Partnership, Gaborone, Botswana. Electronic address: shruthiravimohan@gmail.com.
authors.forename: Shruthi
authors.initials: S
authors.lastname: Ravimohan
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana.
authors.forename: Neo
authors.initials: N
authors.lastname: Tamuhla
authors.affiliation: The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, University of Botswana, Gaborone, Botswana.
authors.forename: Shiang-Ju
authors.initials: SJ
authors.lastname: Kung
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana.
authors.forename: Kebatshabile
authors.initials: K
authors.lastname: Nfanyana
authors.affiliation: Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Botswana-UPenn Partnership, Gaborone, Botswana; The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Steenhoff
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Botswana-UPenn Partnership, Gaborone, Botswana; Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Gross
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Botswana-UPenn Partnership, Gaborone, Botswana.
authors.forename: Drew
authors.initials: D
authors.lastname: Weissman
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Botswana-UPenn Partnership, Gaborone, Botswana; Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Bisson
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016022:Case-Control Studies; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D007111:Immunity, Cellular; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D012129:Respiratory Function Tests; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000150:complications*
chemical_list: D020782:Matrix Metalloproteinases
keywords: ART; HIV; Immune recovery; Lung function; Matrix metalloproteinases; TB-IRIS