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Randomized Controlled Trial
. 2013 Dec 18;8(12):e84585.
doi: 10.1371/journal.pone.0084585. eCollection 2013.

Incidence of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome and impact on patient outcome

Maryline Bonnet  1 , Elisabeth Baudin  1 , Ilesh V Jani  2 , Elizabete Nunes  3 , François Verhoustraten  4 , Alexandra Calmy  5 , Rui Bastos  3 , Nilesh B Bhatt  2 , Christophe Michon  6
Affiliations
Randomized Controlled Trial

Incidence of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome and impact on patient outcome

Maryline Bonnet et al. PLoS One. .

Erratum in

  • PLoS One. 2014;9(1). doi:10.1371/annotation/15d01128-2495-4b95-8fe8-8702190fdb0e

Abstract

Objectives and design: We used data from a randomized trial of HIV-tuberculosis co-infected patients in Mozambique to determine the incidence and predictors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) occurring within 12 weeks of starting antiretroviral therapy, and to evaluate its association with patient outcome at 48 weeks.

Methods: HIV-tuberculosis co-infected and antiretroviral therapy-naïve adults with less than 250 CD4/mm3 were randomized to a nevirapine or efavirenz-based antiretroviral therapy initiated 4 to 6 weeks after starting tuberculosis treatment, and were then followed for 48 weeks. Tuberculosis cases were diagnosed using WHO guidelines, and tuberculosis-IRIS by case definitions of the International Network for the Study of HIV-associated IRIS.

Results: The 573 HIV-tuberculosis co-infected patients who initiated antiretroviral therapy had a median CD4 count of 92 cells/mm(3) and HIV-1 RNA of 5.6 log10 copies/mL. Mortality at week 48 was 6.1% (35/573). Fifty-three (9.2%) patients presented a tuberculosis-IRIS within 12 weeks of starting antiretroviral therapy. Being female and having a low CD4 count, high HIV-1 RNA load, low body mass index and smear-positive pulmonary tuberculosis were independently associated with tuberculosis-IRIS. After adjustment for baseline body mass index, CD4 count and hemoglobin, occurrence of tuberculosis-IRIS was independently associated with 48-week mortality (aOR 2.72 95%CI 1.14-6.54). Immunological and HIV-1 virological responses and tuberculosis treatment outcomes were not different between patients with and without tuberculosis-IRIS.

Conclusion: In this large prospective cohort, tuberculosis-IRIS occurrence within 12 weeks of starting antiretroviral therapy was independently associated with the mortality of HIV-tuberculosis co-infected patients at 48 weeks post antiretroviral therapy initiation.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Study profile.
Figure 2
Figure 2. Evolution of CD4 and HIV-1 RNA among patients with and without TB IRIS.
A CD4 cell count. B. HIV-1 RNA below 50copies/mL.
Figure 3
Figure 3. Probability of death among patients with and without TB-IRIS.
* Log rank test.
See this image and copyright information in PMC

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