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Safety of abacavir therapy after temporary interruptions in patients
without hypersensitivity reactions to the drug
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Juan Berenguera; Belen Padillaa; Vicente Estradab; Carlos Martínc; Pere
Domingod; Jose María Kindeláne; Jose María Ruiz-Guiardinf
AIDS 2002;16:1299-1301
Hypersensitivity reaction to abacavir is a well- characterized, idiosyncratic
reaction of unknown mechanism that has affected 4% of patients treated with
abacavir in all clinical trials to date [1]. Hypersensitivity reaction to
abacavir can be managed by discontinuation of the drug. However, the
re-introduction of abacavir may lead to a life-threatening rechallenge
reaction. During the past year, alarm has been generated by the report of a
severe anaphylactic shock after
rechallenge with abacavir without preceding hypersensitivity reaction [2].
We undertook the present study to assess the safety of abacavir
re-introduction after transient treatment interruptions in patients with no
previous evidence of hypersensitivity reaction. The inclusion criteria of the
study were: confirmed HIV infection, treatment with abacavir, transient
interruption of abacavir and the absence of signs and symptoms of
hypersensitivity reaction before the interruption of abacavir. We considered
transient interruption of abacavir to be
suspension of the drug for 3 days or more. Hypersensitivity reaction was
defined clinically as a multi-system illness with at least two symptoms that
appeared after starting abacavir, which could not be explained by other acute
illness, characteristically worsened after each dose of abacavir, and rapidly
improved after the withdrawal of abacavir. The following information was
obtained from each patient: (i) demographics, such as age and sex; (ii) HIV
data, such as risk
group, Centers for Disease Control and Prevention clinical category, CD4 cell
count, HIV viral load and antiretroviral therapy before and after the
introduction of abacavir; (iii) data regarding abacavir interruption such as
the date of suspension and the date of reinitiation of the drug, the reason
for abacavir suspension, date of the last contact with patients; and (iv)
symptoms and signs present before abacavir interruption or during the
follow-up period after the
reinitiation of abacavir, including fever, rash, gastrointestinal symptoms,
malaise, myalgia, mucosal lesions, respiratory symptoms and hypotension.
A total of 20 patients were included in the study (Table 1), all received
antiretroviral therapy (ART) that included abacavir. There were 12 men and
eight women; their median age was 38 years (interquartile range 35-43).
Fifteen patients acquired HIV infection by injecting drug use and 12 had
previous AIDS-defining conditions. The median CD4 cell count was 181
cells/mm3 [interquartile range (IQR) 67-343] and eight patients had HIV viral
loads below the limit of
detection. There were 25 transitory interruptions of ART including abacavir
(19 patients with one interruption and one patient with six interruptions),
which occurred a median time of 93 days (IQR 57-150) after the initiation of
abacavir. None of the patients had clinical manifestations suggestive of
hypersensitivity reaction before the interruption of abacavir. The reasons
for interruptions were: chemotherapy (n = 7), voluntary abandonment of ART (n
= 6), intolerance or toxicity to drugs other than abacavir (n = 6),
concurrent diseases not related to HIV (n = 5), and surgery (n = 1). The
median duration of the interruption of abacavir therapy was 13 days (IQR
6-41). After the reinstitution of ART with abacavir, patients were followed
up for a median time of 58 days (IQR 28-116), and during that period none
developed clinical manifestations suggestive of rechallenge-like
hypersensitivity reaction to abacavir.
The report by Frissen et al. [2] of severe anaphylactic shock after
rechallenge with abacavir without preceding
hypersensitivity reaction raised our concern because interruptions of
antiretroviral therapy are relatively common for
reasons such as those found in our study, and because abacavir in combination
with two other non-nucleoside reverse
transcriptase inhibitors is an increasingly common regimen for the initial
therapy of HIV infection and for simplification
of highly active antiretroviral therapy in patients with undetectable plasma
HIV-1-RNA levels [3,4].
Further information has been published indicating that treatment
interruptions do not appear to increase the risk of developing a
hypersensitivity reaction to abacavir, and that a rechallenge-type
hypersensitivity reaction, without apparent previous symptoms, is extremely
rare [5]. Our study contributes further evidence about the safety of
re-initiating abacavir after treatment interruptions in patients with no
previous evidence of hypersensitivity reaction at the time of interruption of
the drug.
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