Research Article: Tuberculosis associated immune reconstitution inflammatory syndrome in patients infected with HIV: meningitis a potentially life threatening manifestation

Date Published: May 23, 2012

Publisher: BioMed Central

Author(s): Upasna Agarwal, Amitabh Kumar, Digamber Behera, Martyn A French, Patricia Price.

http://doi.org/10.1186/1742-6405-9-17

Abstract

Tuberculosis (TB) is the most common co infection in HIV-infected persons in India, requiring concomitant administration of anti TB and antiretroviral therapies. Paradoxical worsening of tuberculosis after anti-retroviral therapy (ART) initiation is frequently seen.

To study the frequency, clinical presentation and outcome of paradoxical tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV infected patients in a TB hospital in North India.

A retrospective chart review of HIV-infected TB patients on anti-tubercular treatment (ATT) at time of ART initiation over a 3 year period. Medical records were reviewed for clinical manifestations and outcome in patients who developed TB-IRIS.

514 HIV-infected patients were enrolled between January 2006 and December 2008. Thirteen (12.6%) of 103 patients who had received ART and ATT simultaneously developed paradoxical TB-IRIS. Clinical presentations of paradoxical TB-IRIS included new lymphadenopathy (n = 3), increase in size of existing lymphadenopathy (n = 3), worsening of existing pulmonary lesions (n = 2), appearance of new pleural effusion (n = 1) and prolonged high grade fever (n = 2). Four patients developed new tubercular meningitis as manifestation of TB-IRIS. Our cases developed TB-IRIS a median of 15 days after starting ART (IQR 15–36). TB-IRIS patients were older (> 35 years) than those with no IRIS (P = 0.03), but were not distinguishable by CD4 T-cell count, duration of ATT before ART or the outcome of TB treatment. Eight (62%) patients had a complete recovery while 5 (38%) patients with TB-IRIS died, of which majority (n = 3) had meningitis.

Paradoxical TB-IRIS is a frequent problem during concomitant ATT and ART in HIV-TB co infected patients in north India. Meningitis is a potentially life threatening manifestation of TB-IRIS.

Partial Text

Tuberculosis (TB) is the most common co-infection in HIV-infected persons in high burden countries like India [1]. Many HIV patients consequently require concomitant anti-tubercular treatment (ATT) and antiretroviral therapy (ART). Paradoxical worsening of TB after ART initiation is termed as TB associated immune reconstitution inflammatory syndrome (TB-IRIS) as these exaggerated inflammatory responses are attributed to immune recovery. TB-IRIS is characterized by either deterioration of existing lesions (paradoxical TB-IRIS) or the appearance of new disease associated with previously subclinical infection (unmasking TB-IRIS) after ART initiation [2]. These conditions probably reflect rapid restoration of pathogen-specific immune responses with ART.

This study was a retrospective analysis of prospectively collected data obtained in a structured format from patients with HIV infection and TB disease who were on ATT at time of ART initiation. Detailed case notes were available until the end of ATT, so occurrence of IRIS episode and the time of IRIS development could be accurately analysed.

A total of 514 HIV-infected patients were registered at the HIV clinic of LRS Institute of TB and Respiratory Diseases, New Delhi between January 2006 and December 2008. Of these, 103 patients had received ART and ATT simultaneously and met our inclusion criteria.

Paradoxical TB-IRIS is a clinical entity frequently encountered when ART is initiated in HIV and TB co-infected patients. Understanding of this phenomenon is particularly relevant for HIV clinics in South East Asia and Africa where many patients with active TB enter ART programs [1,7].

The author(s) declare that they have no competing interests.

UA was involved in conception and design of the study, interpretation of data and drafting the manuscript. AK was involved in conception of the manuscript, acquisition of data and revising the manuscript for scientific content. DB was involved in interpretation of data and revising the manuscript for scientific content. PP was involved in drafting the manuscript and interpretation of data. MAF was involved in drafting the manuscript and contributed to the scientific content of the paper. All authors read and approved the final manuscript.

 

Source:

http://doi.org/10.1186/1742-6405-9-17

 

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