ART in early stage of TB therapy results in higher TB IRIS rate
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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