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

AIDS Research and Therapy

Upasna Agarwal¹  Amitabh Kumar¹  Digamber Behera¹  Martyn A French²  Patricia Price² 

[1] LRS Institute of Tuberculosis and Respiratory Diseases, Sri Aurobindo Marg, near Qutab Minar, New Delhi, India, 110 030

[2] School of Pathology and Laboratory Medicine, University of Western Australia, and Department of Clinical Immunology and Immunogenetics, Royal Perth Hospital, Perth, Australia

关键词: Meningitis;    IRIS;    HIV;    Tuberculosis;   

Others  :  789657
DOI  :  10.1186/1742-6405-9-17

 received in 2012-02-18, accepted in 2012-05-08,  发布年份 2012

【 摘 要 】

Background

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.

Objective

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.

Design

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2012 Agarwal et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Sharma SK, Mohan A, Kadhiravan T: HIV-TB co-infection: epidemiology, diagnosis and management. Indian J Med Res 2005, 121:550-567.
• [2]Meintjes G, Lawn SD, Scano G, et al.: Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis 2008, 8:516-523.
• [3]Price P, Murdoch DM, Agarwal U, Lewin SR, Elliott JH, French MA: Immune restoration diseases reflect diverse immunopathological mechanisms. Clin Microbiol Rev 2009, 22:651-663.
• [4]National AIDS Control Organization, Govt. of India: Antiretroviral therapy guidelines for HIV infected adult and adolescents including post exposure prophylaxis. New Delhi 2007.
• [5]Central TB Division, Govt. of India: Managing the Revised National Tuberculosis Control Program in your area. New Delhi 2005.
• [6]Colebunders R, John L, Huyst V, Kambugu A, Scano F, Lyen L: Tuberculosis immune reconstitution inflammatory syndrome in countries with limited resources. Int J Tuberc Lung Dis 2006, 10:946-53.
• [7]Lawn SD, Myer L, Bekker LG, Wood RG: Tuberculosis associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa. AIDS 2007, 21:335-341.
• [8]Agarwal U, Kumar A, Behera D: Profile of HIV associated tuberculosis at a tertiary institute in setting of free anti-retroviral therapy. J Assoc Physicians India 2009, 57:685-690.
• [9]Kumarasamy N, Chaguturu S, Mayer KH, et al.: Incidence of immune reconstitution syndrome in HIV/tuberculosis-co infected patients after initiation of generic antiretroviral therapy in India. J Acquir Immune Defic Syndr 2004, 37:1574-1576.
• [10]Shelburne SA, Visnegarwala F, Darcourt J, Graviss EA, et al.: Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005, 19:399-406.
• [11]Huyst V, Lynen L, Bottieau E, Zolfo M, Kestens L, Colebunders R: Immune reconstitution inflammatory syndrome in an HIV/TB coinfected patient four years after starting antiretroviral therapy. Acta Clin Belg 2007, 62:126-129.
• [12]Tieu HV, Ananworanich J, Avihingsanon A, et al.: Immunologic markers as predictors of tuberculosis-associated immune reconstitution inflammatory syndrome in HIV and tuberculosis coinfected persons in Thailand. AIDS Res Hum Retroviruses 2009, 25:1083-1089.
• [13]Murdoch DM, Venter WDF, Feldman C, Rie AV: Incidence and risk factors for the immune reconstitution inflammatory syndrome in HIV patients in South Africa: a prospective study. AIDS 2008, 22:601-610.
• [14]Dautremer J, Pacanowski J, Girard PM, Lalande V, Sivignon F, Meynard JL: A new presentation of immune reconstitution inflammatory syndrome followed by a severe paradoxical reaction in an HIV-1-infected patient with tuberculous meningitis. AIDS 2007, 21:381-394.
• [15]Vidal JE, Cimerman S, Schiavon Nogueira R, et al.: Paradoxical reaction during treatment of tuberculous brain abscess in a patient with AIDS. Rev Inst Med Trop Sao Paulo 2003, 45:177-178.
• [16]Pepper DJ, Marais S, Maartens G, Rebe K, Morroni C, Rangaka MX, et al.: Neurologic manifestations of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome: a case series. Clin Infect Dis 2009, 48:e96-e107.