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.

CONCLUSION:

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: Gopalan Narendran, Bruno B Andrade, Brian O Porter, Chockalingam Chandrasekhar, Perumal Venkatesan, Pradeep A Menon, Sudha Subramanian, Selvaraj Anbalagan, Kannabiran P Bhavani, Sathiyavelu Sekar, Chandrasekaran Padmapriyadarshini, Satagopan Kumar, Narayanan Ravichandran, Krishnaraj Raja, Kesavamurthy Bhanu, Ayyamperumal Mahilmaran, Lakshmanan Sekar, Alan Sher, Irini Sereti, Soumya Swaminathan
• Journal: PloS one (PLoS One) Vol. 8 Issue 5 Pg. e63541 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23691062 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• C-Reactive Protein

Topics

• C-Reactive Protein (analysis)
• HIV Infections (complications, drug therapy, epidemiology)
• Humans
• Immune Reconstitution Inflammatory Syndrome (diagnosis, epidemiology, etiology)
• Incidence
• India (epidemiology)
• Interleukin-6 (blood)
• Logistic Models
• Prospective Studies
• Statistics, Nonparametric
• Tuberculosis, Pulmonary (complications, drug therapy, epidemiology)