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 Table of Contents  
EVIDENCE BASED MEDICINE
Year : 2019  |  Volume : 17  |  Issue : 1  |  Page : 12-14

Prednisone for the prevention of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome


Date of Web Publication16-Jul-2019

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmi.cmi_16_19

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How to cite this article:
. Prednisone for the prevention of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. Curr Med Issues 2019;17:12-4

How to cite this URL:
. Prednisone for the prevention of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. Curr Med Issues [serial online] 2019 [cited 2019 Aug 25];17:12-4. Available from: http://www.cmijournal.org/text.asp?2019/17/1/12/262823

Summary of Study

Source: This is a summary of the study: prednisone for the prevention of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. New England Journal of Medicine. 2018.[1] Summary prepared by Dr. Ann Helen Prasad, Christian Medical College, Vellore, Tamil Nadu, India.

Clinical Question: Is the use of prophylactic prednisone against paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome safe and effective?

Authors' conclusions: The prophylactic use of prednisone in the first 4 weeks of initiating antiretroviral therapy is safe and effective against paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome


  Why This Study Top


Tuberculosis is the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV).[2] Early initiation of antiretroviral therapy (ART) after the initiation of antituberculosis therapy increases the survival rate of patients affected by both HIV and tuberculosis.[3] However, the early initiation of ART increases the risk of tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS),[3] which increases the morbidity and risk of hospitalization.[4] To prevent IRIS, the use of prophylactic glucocorticoids has been considered.

The administration of adjunctive glucocorticoids in patients with tubercular meningitis and pericarditis reduced mortality and complications.[5],[6] However, in patients who had both HIV and tuberculosis, it increased the risk of adverse events.[7],[8] This study aimed to assess whether prophylactic prednisone safely reduces the incidence of tuberculosis-associated IRIS in patients with HIV infection with fewer than 100 CD4 cells per microliter, who were initiated with ART within 30 days of initiating tuberculosis treatment.




  Results Top


Prednisone was found to be protective against paradoxical tuberculosis-associated IRIS. Thirty-nine (32.5%) participants in the prednisone group and 56 (46.7%) participants in the placebo group developed IRIS according to the International Network for the Study of HIV-associated IRIS (INSHI) criteria.[9] The relative risk (RR) was found to be 0.70 (95% confidence interval [CI], 0.51–0.96; P = 0.03).

Open-label glucocorticoid use (RR, 0.47; 95% CI, 0.27–0.81) and the presence of a major INSHI criterion (RR, 0.57; 95% CI, 0.37–0.87) were rarer in the prednisone than in the placebo group.

Prednisone was safe to use in patients on ART initiated within 30 days of starting antituberculosis treatment. Grade 3 clinical adverse events were rarer in the prednisone group than in the placebo group (RR, 0.80, 95% CI, 0.44–0.89; P = 0.01). Severe infections, Grade 4 clinical adverse events, adverse drug reactions, CD4 counts at week 12, and HIV-1 RNA viral loads were not significantly different between the two groups.


  Discussion Top


Patients infected with HIV are at an increased risk for other opportunistic infections, of which tuberculosis is the most common.[2] Although treating both the HIV and tuberculosis infections simultaneously is reported to have better patient survival rates, it is also complicated by the development of the paradoxical tuberculosis-associated IRIS.[3] IRIS is an inflammatory state that worsens the inflammatory features of tuberculosis such as fever, lymphadenitis, and pulmonary infiltration. It can be severe enough to warrant hospitalization.[4]

In patients with tubercular meningitis and pericarditis (without HIV infection), glucocorticoids have been successfully used to reduce the inflammatory complications.[5],[6] Since IRIS is an inflammatory reaction, it was hypothesized that the use of glucocorticoids could reduce the risk of IRIS. However, the use of glucocorticoids in the early phase of ART has been reported to increase the mortality and risk of hospitalization associated with HIV-related cancers, such as Kaposi's sarcoma.[7],[8] However, in these previous studies, either glucocorticoid other than prednisone or high doses of prednisone were used.

In this study, a low dose of prednisone (40 mg/day for 14 days followed by 20 mg/day for 14 days) initiated within 48 h of ART was used to determine whether the prophylactic use of prednisone is safe and effective against tuberculosis-associated IRIS in patients at high risk for developing it.

The study shows that the prophylactic use of prednisone is safe in patients with HIV and tuberculosis who are being initiated on ART within 30 days of starting antituberculosis treatment. Grade 3 adverse reactions were rarer in patients who were administered prednisone than those who were administered the placebo regimen; whereas, other complications were not significantly different between the two groups. This study found that low-dose prednisone administered within 48 h of initiating ART that is started within 30 days of antituberculosis treatment is protective against paradoxical tuberculosis-associated IRIS.


  Strengths Top


This clinical trial included patients who had a high risk of developing IRIS (47% of the placebo group had developed tuberculosis-associated IRIS) and showed conclusively that the risk of developing IRIS was significantly brought down by administering prophylactic prednisone.

The glucocorticoid and the low-dose, short-course regimen chosen for this study was safer than those used in other studies.


  Limitations Top


The study population was chosen from a clinic with ambulatory patients. Hence, the results cannot be generalized to hospitalized patients.

The study did not have a sufficient sample size to evaluate differences in mortality between the two groups.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Meintjes G, Stek C, Blumenthal L, Thienemann F, Schutz C, Buyze J, et al. Prednisone for the prevention of paradoxical tuberculosis-associated IRIS. N Engl J Med 2018;379:1915-25.  Back to cited text no. 1
    
2.
Ford N, Shubber Z, Meintjes G, Grinsztejn B, Eholie S, Mills EJ, et al. Causes of hospital admission among people living with HIV worldwide: A systematic review and meta-analysis. Lancet HIV 2015;2:e438-44.  Back to cited text no. 2
    
3.
Uthman OA, Okwundu C, Gbenga K, Volmink J, Dowdy D, Zumla A, et al. Optimal timing of antiretroviral therapy initiation for HIV-infected adults with newly diagnosed pulmonary tuberculosis: A systematic review and meta-analysis. Ann Intern Med 2015;163:32-9.  Back to cited text no. 3
    
4.
Namale PE, Abdullahi LH, Fine S, Kamkuemah M, Wilkinson RJ, Meintjes G. Paradoxical TB-IRIS in HIV-infected adults: A systematic review and meta-analysis. Future Microbiol 2015;10:1077-99.  Back to cited text no. 4
    
5.
Dooley DP, Carpenter JL, Rademacher S. Adjunctive corticosteroid therapy for tuberculosis: A critical reappraisal of the literature. Clin Infect Dis 1997;25:872-87.  Back to cited text no. 5
    
6.
Critchley JA, Young F, Orton L, Garner P. Corticosteroids for prevention of mortality in people with tuberculosis: A systematic review and meta-analysis. Lancet Infect Dis 2013;13:223-37.  Back to cited text no. 6
    
7.
Mayosi BM, Ntsekhe M, Bosch J, Pandie S, Jung H, Gumedze F, et al. Prednisolone and mycobacterium indicus pranii in tuberculous Thomas: Prednisone for the prevention of paradoxical tuberculosis-associated IRIS pericarditis. N Engl J Med 2014;371:1121-30.  Back to cited text no. 7
    
8.
Elliott AM, Luzze H, Quigley MA, Nakiyingi JS, Kyaligonza S, Namujju PB, et al. Arandomized, double-blind, placebo-controlled trial of the use of prednisolone as an adjunct to treatment in HIV-1-associated pleural tuberculosis. J Infect Dis 2004;190:869-78.  Back to cited text no. 8
    
9.
Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: Case definitions for use in resource-limited settings. Lancet Infect Dis 2008;8:516-23.  Back to cited text no. 9
    




 

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