Tuberculosis immune reconstitution inflammatory syndrome in A5221 STRIDE: timing, severity, and implications for HIV-TB programs.

TitleTuberculosis immune reconstitution inflammatory syndrome in A5221 STRIDE: timing, severity, and implications for HIV-TB programs.
Publication TypeJournal Article
Year of Publication2014
AuthorsLuetkemeyer AF, Kendall MA, Nyirenda M, Wu X, Ive P, Benson CA, Andersen JW, Swindells S, Sanne IM, Havlir DV, Kumwenda J
Corporate AuthorsAdult AIDS Clinical Trials Group A5221 Study Team
JournalJ Acquir Immune Defic Syndr
Volume65
Issue4
Pagination423-8
Date Published2014 Apr 1
ISSN1944-7884
KeywordsAdult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Female, HIV Infections, Humans, Immune Reconstitution Inflammatory Syndrome, Male, Severity of Illness Index, Time Factors, Tuberculosis
Abstract

RATIONALE AND OBJECTIVES: 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.

METHODS AND MEASUREMENTS: 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 exact, Wilcoxon, and log-rank tests were used for comparisons.

MAIN RESULTS: TB IRIS occurred in 61 (7.6%) patients: 10.4% in earlier vs. 4.7% in later ART, 11.5% with CD4 <50 vs. 5.4% with CD4 ≥50 cells per cubic millimeter. 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%); central nervous system 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%.

CONCLUSIONS: TB IRIS was more frequent with earlier ART initiation and CD4 <50 cells per cubic millimeter. As ART is implemented earlier in HIV-TB coinfection, programs will require the diagnostic capabilities, clinical resources, and training necessary to manage TB IRIS.

DOI10.1097/QAI.0000000000000030
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID24226057
PubMed Central IDPMC3943693
Grant ListP30 AI027763 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069399 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069456 / AI / NIAID NIH HHS / United States
UM1 AI069463 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States