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High Risk of Unrecognized Adrenal Suppression and Symptoms of Steroid Excess in HIV+ Clinic Patients Exposed to Ritonavir and Topical Fluticasone: Results of a Case-control Study
Mark Hull*1,2, E Phillips1,3, M Harris2,3, G Bondy4, P Leong4, J Toy4, R Hogg1,3, J Singer1,2, and J Montaner1,2,3
1Univ of British Columbia, Vancouver, Canada; 2Canadian HIV Trials Network, Vancouver, Canada; 3BC Ctr for Excellence in HIV/AIDS, Vancouver, Canada; and 4St. Paul's Hosp, Vancouver, BC, Canada
Background:
Case reports
of exogenous steroid excess and adrenal insufficiency in patients on inhaled or
nasal fluticasone propionate (FP)-
and ritonavir (RTV)-containing protease inhibitor (PI)
regimens have underscored the potential for this interaction.
Methods:
To determine
whether unsuspected adrenal suppression occurs in HIV+ patients
using RTV/FP in a clinic setting, fasting morning cortisol
screening was done on sequential unselected patients undergoing routine HIV
follow-up at St Paul’s Hospital Immunodeficiency
Clinic, Vancouver, British Columbia, between July and October
2005. Cases, defined as those with a cortisol value
<100 nmol/L were assessed for symptoms of either
adrenal suppression or exogenous steroid excess. Controls were those with a normal
fasting serum cortisol (175 to 685 nmol/L). All patients who underwent cortisol screening had their medication records abstracted
from both the provincial ART and prescription drug databases (Pharmanet); p
values were calculated for the comparison between cases and the unmatched
control group for the RTV/FP pharmacologic interaction as a cause of a
suppressed fasting cortisol.
Results:
We screened 50
patients. The average age was 49 years and 88% were male; 92% were on ART, and
87% of the ART regimens contained RTV-boosted PI; 7 patients had suppressed
fasting cortisols (<28 nmol/L
in all 7), and 43 patients (controls) were unsuppressed. All 7 were on RTV-containing
PI regimens and FP (inhaled = 6, nasal = 1) vs only 1
control (p <0.0001, Fishers exact
test). Of 7 cases, 6 were virologically suppressed,
with a median CD4 of 340/mm3 (240 to 430). The median time on ART
regimens was 8 months (range 2 to 15months) and 6 of the 7 had been on FP
>10 months. Of the 7 adrenally suppressed patients,
3 were asymptomatic and 4 were symptomatic: 2 had Cushingoid
features, 1 had easy bruising, and 1 experienced loss of diabetic control.
Conclusions:
A high
proportion of RTV/FP-exposed patients were identified with suppressed fasting cortisols (7 of 8; 88%), including 57% with associated but unrecognized
symptoms, highlighting the need for increased clinical vigilance. RTV/FP combinations
should be avoided where alternatives exist, and routine fasting cortisol screening applied in patients on this combination.
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