A low CD4 cell
count increases the risk of immune reconstitution inflammatory syndrome (IRIS)
for people starting antiretroviral therapy (ART) within two weeks of treatment
for tuberculosis (TB), investigators report in the online edition of the Journal of Acquired Immune Deficiency
Syndromes. The timing of antiretroviral therapy had no impact on the risk
of IRIS for people with a CD4 count above 50 cells/mm3.
risk of TB IRIS with earlier ART is concentrated in those with very low CD4
cell counts,” write the authors.
showed that approximately a third of patients required an invasive procedure to
manage their IRIS, a finding that the authors believe has implications for the
resourcing, planning and delivery of ART-TB programmes.
Globally, TB is
the leading cause of serious illness and death in people with HIV. To reduce
the risk of mortality, people with HIV and TB often need to start ART soon
after they start TB therapy. But the risk of a paradoxical IRIS – the
worsening of TB symptoms despite effective treatment – means that the
initiation of ART is usually delayed until two weeks of TB therapy have been
the international A5221 STRIDE study wanted to establish a clearer
understanding of the risk and severity of TB IRIS according to whether patients
started early ART (within two weeks of initiating TB treatment) or delayed ART
(after eight to twelve weeks of TB therapy) and also according to whether they
had a CD4 cell count above or below 50 cells/mm3.
population included 806 people, all of whom were ART naive (had not taken HIV treatment before) and had a CD4 cell
count below 250 cells/mm3. The study participants were recruited between 2006
to 2009 and were randomised to receive early or delayed ART.
TB IRIS occurred
in 8% of participants, an overall incidence of 9.0 per 100 person-years.
The rate was
twice as high among people who started early versus delayed ART (10 vs 5%)
and also in people with a CD4 cell count below 50 cells/mm3
compared to a CD4 cell count above that level (12 vs 5%, p = 0.014).
In people with a
CD4 cell count above 50 cells/mm3, there was no difference in the
rate of IRIS according to ART initiation (early = 6% vs delayed = 5%).
Almost all (93%)
IRIS cases involved major symptoms, such as new or worsening lymphadenopathy,
radiological manifestations and serositis. Common minor IRIS symptoms included
constitutional symptoms such as fevers, night sweats and weight loss or cough.
developed sooner in people who took early compared to delayed ART (29 vs 82
days, p < 0.001).
were used for the treatment of 54% of people who experienced IRIS and the median duration of
therapy was 15 days. Just over a third of patients (34%) had an invasive
procedure to manage their IRIS.
There were no
deaths and only six people – three in each arm of the study – interrupted their HIV therapy for seven days
Overall, 31% of
cases were classified as severe and required hospitalisation; 41% were
moderate, requiring therapy with steroids or an invasive procedure and the
remaining 28% were mild.
IRIS severity did
not differ according to the use of early or delayed HIV therapy.
“TB IRIS was more
common in participants with earlier ART initiation and CD4 cell
counts < 50 cell/mm3,” conclude the authors. “As ART is
increasingly implemented within 2 weeks after TB treatment initiation to reduce
AIDS-related complications and mortality, HIV-TB programmes will need
diagnostic capabilities, clinical resources and provider training necessary to
diagnose and manage tuberculosis-related immune reconstitution inflammatory