title: Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in HIV patients with culture confirmed pulmonary tuberculosis in India and the potential role of IL-6 in prediction.
abstract: BACKGROUND
  The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively.
  
  
  METHODS
  HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS.
  
  
  RESULTS
  Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14-47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7-16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9-23). Two patients died due to CNS TB-IRIS. Lower CD4(+) T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis.
  
  
  CONCLUSIONS
  Paradoxical TB-IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions.
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Gopalan
authors.initials: G
authors.lastname: Narendran
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Andrade
authors.forename: Brian O
authors.initials: BO
authors.lastname: Porter
authors.forename: Chockalingam
authors.initials: C
authors.lastname: Chandrasekhar
authors.forename: Perumal
authors.initials: P
authors.lastname: Venkatesan
authors.forename: Pradeep A
authors.initials: PA
authors.lastname: Menon
authors.forename: Sudha
authors.initials: S
authors.lastname: Subramanian
authors.forename: Selvaraj
authors.initials: S
authors.lastname: Anbalagan
authors.forename: Kannabiran P
authors.initials: KP
authors.lastname: Bhavani
authors.forename: Sathiyavelu
authors.initials: S
authors.lastname: Sekar
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Padmapriyadarshini
authors.forename: Satagopan
authors.initials: S
authors.lastname: Kumar
authors.forename: Narayanan
authors.initials: N
authors.lastname: Ravichandran
authors.forename: Krishnaraj
authors.initials: K
authors.lastname: Raja
authors.forename: Kesavamurthy
authors.initials: K
authors.lastname: Bhanu
authors.forename: Ayyamperumal
authors.initials: A
authors.lastname: Mahilmaran
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Sekar
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000175:diagnosis* / Q000453:epidemiology* / Q000209:etiology*; D015994:Incidence; D007194:India / Q000453:epidemiology; D015850:Interleukin-6 / Q000097:blood; D016015:Logistic Models; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology
chemical_list: D015850:Interleukin-6; D002097:C-Reactive Protein