Immune
reconstitution inflammatory syndrome, or IRIS, refers to a worsening or flare-up
of a pre-existing infection soon after starting antiretroviral therapy, as patients
begin to experience immune recovery. Corticosteroid drugs -- which suppress overall
immune function -- are used to treat IRIS, but are associated with adverse side
effects.
In the January 30, 2007 issue of AIDS, British physicians
reported on a case in which the drug montelukast (Singulair) -- which is usually
prescribed to treat asthma -- appeared to improve symptoms of IRIS. Montelukast
inhibits leukotrienes, a family of immune system chemicals that play a role in
inflammation.
Case Report
•
The patient was 59-year-old HIV positive Caucasian man seen at Royal Free Hospital
in London.
•
Prior to interrupting therapy, he had been highly adherent, and his CD4 cell count
had increased from 36 to 800 cells/mm3.
•
5 months after interrupting therapy, his CD4 count
had fallen to 226 cells/mm3 and his HIV viral load had risen to 35,000 copies/mL. •
3 weeks after restarting HAART,
he developed a case of acute urticaria (hives).
•
At this time, his
CD4 count was unchanged, his HIV viral load had fallen to about 200 copies/mL,
and he had an elevated neutrophil count and an increased blood level of C-reactive
protein (a marker of inflammation).
•
The patient started
treatment with 2 antihistamines, cetirizine (Zyrtec) and ranitidine (Zantac),
but his hives worsened and he developed other symptoms including fever.
•
He then started a
1-month course of oral prednisone (a corticosteroid) and experienced resolution
of symptoms.
•
Within 2 days after
stopping prednisone, his hives returned, along with fever and a rapid heartbeat.
•
The man then started
on 10 mg/day montelukast, which led to symptom resolution and normalization of
inflammatory blood markers within 5 days.
•
The patients stopped
taking montelukast after 3 months, and at this time his symptoms did not recur.
•
The man remained on
HAART and achieved undetectable HIV viral load and a doubled CD4 count.
Conclusion
On
the basis of this case, the authors suggested that leukotrienes may play a role
in the development of IRIS, and that leukotriene inhibitors may therefore alleviate
IRIS without causing significant overall immune suppression.
02/13/07
Reference M
C Lipman and S K Carding. Successful drug treatment of immune reconstitution disease
with the leukotriene receptor antagonist, montelukast: a clue to pathogenesis?
AIDS 21(3): 383-384. January 30, 2007.
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