July 26, 2005
Several studies in this conference addressed the issue of abacavir (ABC, Ziagen)-related hypersensitivity reaction (HSR) in both the treatment-naive and -experienced populations. The incidence of hypersensitivity reaction in patients who are naive to abacavir therapy has been a point of controversy since the initial studies were done for this drug's approval. Even after the release of zidovudine/lamivudine/abacavir (AZT/3TC/ABC, Trizivir) and the subsequent approval of the fixed-dose combination of zidovudine/lamivudine (AZT/3TC, Combivir), the estimated incidence of this reaction has been somewhat variable.
Historically, most cases of hypersensitivity reaction have been reported during the first 6 weeks after an abacavir-containing regimen is initiated, with a median onset time of 9 days. A review of data from more than 9,000 subjects in 37 clinical trials to date, using abacavir both once and twice daily, yielded an overall rate of abacavir hypersensitivity reaction of 5-4% (range 0-14%) and demonstrated that the frequency of abacavir administration (i.e., twice daily versus once daily) was not a risk factor for abacavir hypersensitivity reaction.
One of the studies on this subject at IAS was presented by Patrick Yeni from CHU Bichat-Claude Bernard in Paris. The incidence and severity of suspected abacavir hypersensitivity reaction was determined in a large treatment-naive cohort treated with the fixed-dose combination of abacavir/lamivudine (ABC/3TC, Epzicom, Kivexa) and a protease inhibitor.
For this analysis, data from the KLEAN study, a large open-label multicenter study was analyzed. Patients in this study were treated with twice-daily fosamprenavir (FPV, 908, Lexiva, Telzir) 700 mg + twice-daily ritonavir (RTV, Norvir) 100 mg versus lopinavir/ritonavir (LPV/r, Kaletra) twice daily, both with abacavir/lamivudine once daily over 48 weeks.
During the first 6 weeks of the study, the incidence of hypersensitivity reaction was 5.9%, which is consistent with previously published data on other studies using once-daily abacavir. The median time to the onset of these symptoms was about 8 days. In addition, the rate of severe (Grade 3 or 4) abacavir hypersensitivity reaction was low (2%) and similar to previously reported data for 300-mg twice-daily abacavir and the 600-mg once-daily dose.
In a related presentation, researchers addressed the potential development of hypersensitivity reaction in patients who have been reexposed to abacavir after having been previously treated with another abacavir-containing formulation. The risk is that during their first exposure to abacavir these patients may have developed unrecognized hypersensitivity reaction. Because of this, there is the potential risk of a more severe reaction for these patients while taking this new regimen.
To answer this question, the Trizivir Epidemiology Program Team was created to mine data from different cohorts and to determine the denominator for hypersensitivity reaction-like events (HSR-LE) based on a first exposure and a rechallenge enumerator based on abacavir last exposure on those patients.
Potential cases were identified from the observational databases and medical records from the Department of Veterans Affairs, Ingenix, HIV insight and CHORUS databases. An HSR-LE was defined as a patient with abacavir discontinuation within 90 days of initiation associated with at least one event, condition or symptoms consistent with hypersensitivity reaction. This determination was made by an Expert Medical Review Board. Any reexposure to abacavir in a patient already identified as HSR-LE was considered part of the enumerator. Relative risks of events for abacavir and zidovudine/lamivudine/abacavir were assessed by odds ratios and 95% CI using zidovudine/lamivudine/abacavir as reference.
A simpler way to understand this analysis is a ratio of:
|All patients who were rechallenged|
with an abacavir formulation
|From all the patients with a history of|
an HSR-LE who initially received abacavir
The results observed from these data are summarized below:
In summary, the number of abacavir hypersensitivity reaction events was relatively low. There were also no meaningful differences between the abacavir and the zidovudine/lamivudine/abacavir groups. The risk of rechallenge was similar for either zidovudine/lamivudine/abacavir or abacavir alone.
These two studies add more information with respect to the safety of using abacavir, either as a once-daily or twice-daily medication in the abacavir-naive population. It also reassures us regarding the low probability of abacavir hypersensitivity reaction after a rechallenge with another abacavir-containing formulation in patients who may have a non-definitive prior history of abacavir hypersensitivity reaction.
Abstract: Reported incidence and severity of suspected abacavir hypersensitivity reactions (HSR) through at least 6 weeks in a large, controlled clinical trial using a once-daily (OAD) abacavir 600 mg/lamivudine 300 mg tablet (ABC/3TC FDC) dual nucleoside backbone with a boosted protease inhibitor: the KLEAN study (Poster TuPe2.4C08)
Authored by: S Becker, P Yeni, D Sutherland-Phillips, P Wannamaker, J Hernandez, C Brothers, L Yau, C Humphries, S Griffith, M Shaefer
Affiliations: Pacific Horizon Medical Group, San Francisco, United States of America, 2CHU Bichat-Claude Bernard, Paris, France, 3GlaxoSmithKline, Research Triangle Park, United States of America
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This abstract cannot be linked to directly, but is available within this listing.
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