HLA-B*5701
Genetic Test Predicts Risk of Abacavir Hypersensitivity
By
Liz Highleyman Treatment
with abacavir (Ziagen, also a
component of the combination pills Trizivir
and Epzicom) is associated with
a significant risk of drug hypersensitivity, ranging from 3% to 9% in various
studies. The reaction is characterized by nausea, abdominal pain, fever, skin
rash, shortness of breath, cough, and/or sore throat. If abacavir is discontinued
due to hypersensitivity and restarted in the future, a life-threatening reaction
may occur. Previous
research has shown that abacavir hypersensitivity is associated with a genetic
variation known as the HLA-B*5701 allele, which
occurs most frequently among Caucasians. At the 7th Workshop on Clinical Pharmacology
of HIV Therapy in April, for example, Elizabeth Phillips, MD, and colleagues reported
that in an international study, 23 out of 46 participants with positive patch
tests for abacavir hypersensitivity carried the HLA-B*5701 allele, compared with
only two out of 23 individuals with a negative patch test. Six patients with previous
suspected hypersensitivity reactions who tested negative for HLA-B*5701 did not
experience hypersensitivity after abacavir was reintroduced with careful monitoring. In
the July 1, 2006 issue of Clinical Infectious Diseases, Australian researchers
reported data from a prospective study in which 260 abacavir-naïve individuals
underwent genetic testing to screen for abacavir hypersensitivity risk. Results
7.7% of the 260 patients tested positive for the HLA-B*5701 allele.
None of the 148 patients who tested negative for the HLA-B*5701 allele and started
abacavir developed a hypersensitivity reaction (6 discontinued abacavir for other
reasons).
Three patients who tested positive for the HLA-B*5701 allele started treatment
with abacavir (two did so before test results were available; the other had limited
treatment options and decided to accept the risk), and all developed symptoms
of hypersensitivity.
The incidence of true abacavir hypersensitivity reactions at this center decreased
from 8% before genetic testing to 2% after implementation of the genetic screening
protocol.
Conclusion
The
researchers concluded that their study "confirm[ed] the usefulness of genetic
risk stratification" using the HLA-B*5701 screening test for abacavir sensitivity.
In
an accompanying editorial, Phillips asked whether genetic testing for abacavir
hypersensitivity is ready for widespread clinical use. She stated that while HLA-B*5701
screening can prevent true hypersensitivity reactions, and may make it less likely
that people who are not prone to hypersensitivity will be falsely diagnosed as
hypersensitive and unnecessarily taken off the drug, the test is not a substitute
for clinical judgment or "pharmacovigilence."
She
noted that the cost effectiveness of the test would depend on the prevalence of
the HLA-B*5701 allele in a population, which ranges from about 8% among Caucasians
(meaning about 14 patients would have to be screened to prevent one case of hypersensitivity)
to less than 1% among Africans and Asians. Phillips
concluded that large controlled trials should be conducted to confirm the test's
utility; GlaxoSmithKline, the manufacturer of abacavir, is currently planning
such a trial for Europe and Australia. "At this time," she wrote, "HLA-B*5701
screening is best positioned as a screening test for abacavir-naïve populations
and should not be used as a rationale for rechallenge in abacavir-exposed individuals." 7/18/06 References A
Rauch, D Nolan, A Martin, and others. Prospective Genetic Screening Decreases
the Incidence of Abacavir Hypersensitivity Reactions in the Western Australian
HIV Cohort Study. Clinical Infectious Diseases 43(1): 99-102. July 1, 2006. E
J Phillips. Genetic Screening to Prevent Abacavir Hypersensitivity Reaction: Are
We There Yet? Clinical Infectious Diseases 43(1): 103-105. July 1, 2006.
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