Starting antiretroviral therapy (ART) in the early stage of treatment for tuberculosis (TB) resulted in a significantly higher rate of TB immune reconstitution inflammatory syndrome (IRIS) in Durban, South Africa. People who started ART early during TB therapy also had more severe IRIS and a longer time to IRIS resolution.
Concern about TB IRIS remains a barrier to ART in many regions with coepidemic TB and HIV infection. To assess IRIS incidence and outcomes relative to the timing of ART, SAPiT Trial investigators analyzed IRIS data in the three arms of this randomized open-label trial.
SAPiT randomized 642 people coinfected with TB and HIV to start ART within 4 weeks of starting TB therapy (early integrated treatment group), within 4 weeks of completing the intensive phase of TB treatment (late integrated treatment group), or within 4 weeks of finishing TB therapy (sequential treatment group). In the trial’s primary analysis, early integrated ART in people with a CD4 count below 50 cells/µL increased AIDS-free survival, but late integrated ART in people with higher CD4 counts reduced risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death (Abdool Karim SS, et al. New England Journal of Medicine. 2011; 365: 1492-1501).
The IRIS analysis involved all 642 patients randomized in SAPiT at an outpatient clinic in Durban, South Africa. The researchers defined IRIS as “new-onset or worsening symptoms, signs, or radiographic manifestations temporally related to treatment initiation, accompanied by a treatment response.”
In the early integrated, late integrated, and sequential treatment groups, IRIS incidence was 19.5, 7.5, and 8.1 cases per 100 person-years. Among people with a pre-ART CD4 count below 50 cells/µL, IRIS incidence in the three groups was 45.5, 9.7, and 19.7 per 100 person-years.
Statistical analysis determined that IRIS incidence was more than twice higher in the early integrated group than in the late integrated group (incidence rate ratio [IRR] 2.6, 95% confidence interval [CI] 1.5 to 4.8, P < 0.001) or in the sequential group (IRR 2.4, 95% CI 1.4 to 4.4, P < 0.001).
More severe IRIS affected the early integrated treatment group more than the other two groups (35% versus 19%, P = 0.179). People randomized to early integrated treatment had a higher hospital admission rate (42% versus 14%, P = 0.007) and a longer time to IRIS resolution (70.5 versus 29.0 days, P = 0.001).
The SAPiT team notes that their findings “are particularly relevant to patients initiating ART with a CD4 count less than 50 cells/µL, given the increased survival benefit of early ART initiation in this group.”
They propose that “deferring ART initiation by as much as 12 weeks after tuberculosis treatment initiation may be an appropriate strategy in stable ambulatory patients with a CD4 count of 50 cells/µL or greater because this approach offers lower incidence and severity of IRIS without increasing the risk for AIDS or death.”
Source: Kogieleum Naidoo, Nonhlanhla Yende-Zuma, Nesri Padayatchi, Kasavan Naidoo, Niraksha Jithoo, Gonasagrie Nair, Sheila Bamber, Santhana Gengiah, Wafaa M. El-Sadr, Gerald Friedland, Salim Abdool Karim. The immune reconstitution inflammatory syndrome after antiretroviral therapy initiation in patients with tuberculosis: findings from the SAPiT trial FREE. Annals of Internal Medicine. 2012; 157: 313-324.
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