TB IRIS more frequent with earlier ART at under 50 CD4s in ACTG trial
Tuberculosis immune reconstitution inflammatory syndrome (TB IRIS) occurred more often with early antiretroviral therapy (ART) than with delayed therapy in the randomized ACTG A5221 trial. TB IRIS proved more common in people who started ART with a CD4 count below 50 cells/µL.
Several studies found higher rates of TB IRIS in people who start ART sooner after TB therapy begins. Starting ART soon after TB therapy begins is generally recommended because of lower mortality with early versus delayed ART. In the four-continent ACTG A5221 trial, early ART lowered rates of new AIDS illness and death in people with a pretreatment CD4 count below 50 cells/µL (Havlir DV, et al. New England Journal of Medicine. 2011; 365: 1482-1491).
The TB IRIS analysis involved 806 trial participants. The early-ART group started antiretrovirals within 2 weeks of starting TB therapy, while the delayed-ART group started 8 to 12 weeks after beginning TB therapy. Researchers defined TB IRIS as severe (hospitalization or death), moderate (corticosteroid use or invasive procedure), or mild (no hospitalization, procedures, or steroids).
TB IRIS developed in 61 patients (7.6%), including 10.4% in the early-ART group and 4.7% in the delayed-ART group. TB IRIS arose in 11.5% of participants with a pre-ART CD4 count below 50 cells/µL versus 5.4% of those with an initial CD4 count at or above 50 cells/µL. The interaction between ART arm and initial CD4 count was statistically significant (P = 0.014). Almost half of TB IRIS cases, 44.3%, developed in people who started ART early and with a sub-50 CD4 count.
TB IRIS arose at a median of 29 days after TB therapy started in the early-ART group and 82 days in the deferred-ART group (P < 0.001). TB IRIS was mild in 27.9% of cases, moderate in 41.0%, and severe in 31.1%. No one died because of TB IRIS.
Manifestations of TB IRIS were lymphadenopathy in 59.0%, constitutional symptoms in 54.1%, and radiographic changes in 41.0%. Only 6.6% of IRIS cases involved the central nervous system.
IRIS management required corticosteroids in 54.1% of cases, one or more invasive procedures in 34.4%, and hospital admission in 31.1%.
“As ART is implemented earlier in HIV-TB coinfection,” the researchers advise, “programs will require the diagnostic capabilities, clinical resources, and training necessary to manage TB IRIS.”
Source: Anne F. Luetkemeyer, Michelle A. Kendall, Mulinda Nyirenda, Xingye Wu, Prudence Ive, Constance A. Benson, Janet W. Andersen, Susan Swindells, Ian M. Sanne, Diane V. Havlir, Johnstone Kumwenda, the Adult AIDS Clinical Trials Group A5221 study team. Tuberculosis immune reconstitution inflammatory syndrome in A5221 STRIDE: timing, severity, and implications for HIV-TB programs. JAIDS. 2014; 65: 423-428.
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For primary results of ACTG A5221