Tuberculosis Immune Reconstitution Inflammatory Syndrome in A5221 STRIDE: Timing, Severity and Implications for HIV-TB programs.

HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco Center for Biostatistics in AIDS Research, Harvard School of Public Health College of Medicine, Blantyre, Malawi Center for Biostatistics in AIDS Research, Harvard School of Public Health Faculty of Heath Sciences, University of the Witwatersrand Antiviral Research Center, University of California, San Diego Center for Biostatistics in AIDS Research, Harvard School of Public Health Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE Faculty of Health Sciences, University of the Witwatersrand HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco College of Medicine, Blantyre, Malawi, Adult AIDS Clinical Trials Group A5221 Study Team.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 11/2013; DOI: 10.1097/QAI.0000000000000030
Source: PubMed

ABSTRACT Earlier initiation of antiretroviral therapy (ART) in HIV-tuberculosis(TB) is associated with increased immune reconstitution inflammatory syndrome (IRIS). The severity, frequency and complications of TB IRIS were evaluated in A5221, a randomized trial of earlier ART (within 2 weeks after TB treatment initiation) vs. later ART (8-12 weeks after TB treatment) in HIV-infected patients starting TB treatment.
In 806 participants, TB IRIS was defined using published clinical criteria. Cases were classified as severe(hospitalization/death), moderate(corticosteroid use/invasive procedure), or mild(no hospitalization/procedures/steroids). Fisher's Exact, Wilcoxon, and log rank tests were used for comparisons.
TB IRIS occurred in 61 (7.6%) patients: 10.4% in earlier vs. 4.7% later ART, 11.5% with CD4 < 50 vs. 5.4% CD4 ≥ 50 cells/mm. The CD4/ART arm interaction was significant, p=0.014, with 44.3% of TB IRIS occurring with CD4 < 50 and earlier ART. TB IRIS occurred sooner with earlier vs. later ART initiation, at a median of 29 vs. 82 days after TB treatment initiation (p<0.001). IRIS manifestations included lymphadenopathy(59.0%), constitutional symptoms(54.1%), and radiographic changes(41.0%); CNS TB IRIS was uncommon (6.6%). TB IRIS was mild in 27.9%, moderate in 41.0%, and severe in 31.1%. No TB IRIS-associated deaths occurred. IRIS management required ≥ 1 invasive procedures in 34.4%, hospitalization in 31.1% and corticosteroids in 54.1%.
TB IRIS was more frequent with earlier ART initiation and CD4 <50 cells/mm. As ART is implemented earlier in HIV-TB co-infection, programs will require the diagnostic capabilities, clinical resources and training necessary to manage TB IRIS.

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Dec 10, 2014