Abacavir adverse reactions related with HLA-B57: 01 haplotype in a large cohort of patients infected with HIV
Carriage of human leukocyte antigen (HLA)-B*57:01 allele increases the risk of abacavir hypersensitivity reaction. Therefore, since 2008 HIV treatment guidelines recommend HLA-B*57:01 screening before abacavir administration, greatly reducing hypersensitivity reaction rate. However, clinically suspe...
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| Published in: | Pharmacogenetics and genomics Vol. 30; no. 8; p. 167 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
01.10.2020
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| Subjects: | |
| ISSN: | 1744-6880, 1744-6880 |
| Online Access: | Get more information |
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| Summary: | Carriage of human leukocyte antigen (HLA)-B*57:01 allele increases the risk of abacavir hypersensitivity reaction. Therefore, since 2008 HIV treatment guidelines recommend HLA-B*57:01 screening before abacavir administration, greatly reducing hypersensitivity reaction rate. However, clinically suspected abacavir-related hypersensitivity reactions are described in allele non-carriers. Major aim of this study was to evaluate the relationship between HLA-B*57:01 pattern and abacavir-related hypersensitivity reaction, focusing on hypersensitivity reaction prevalence in allele non-carriers.
We included all outpatients aged >18 years old with HIV infection and known HLA-B*57:01 pattern, followed at our Department from January 2000 until December 2017. Patients were divided according to HLA-B*57:01 pattern and first antiretroviral treatment prescribed (containing or not abacavir) as follows: HLA-B*57:01 allele carriers treated with abacavir and HLA-B*57:01 allele non-carriers treated with abacavir. We considered all adverse events reported during first abacavir administration, differentiating between confirmed hypersensitivity reactions and non-hypersensitivity reactions, according to abacavir hypersensitivity reaction definition included in the abacavir EU Summary of Product Characteristics and the US Prescribing Information.
A total of 3144 patients had a known HLA-B*57:01 pattern. About 5.4% of them showed allele polymorphism; Caucasian ethnicity was the most represented. In this cohort, 1801 patients were treated with a first abacavir-containing regimen (98.2% of them was represented by allele non-carriers). 191 out of 1801 patients discontinued abacavir because of toxicity/intolerance; among them 107 described adverse events fulfilled the criteria of confirmed abacavir hypersensitivity reaction (22/32 allele-positive patients and 85/1769 allele-negative patients). After having experienced a confirmed abacavir hypersensitivity reaction, abacavir was re-administered to eight HLA-B*57:01 negative patients. Seven of them re-experienced a syndrome consistent with hypersensitivity reaction, finally leading to drug discontinuation. Overall, no fatal reactions were described.
Not all abacavir-related side effects occur as a result of classic HLA-B*57:01-mediated hypersensitivity reaction, as they can develop irrespective of HLA-B*57:01 status. Clinical vigilance must be an essential part of the management of individuals starting abacavir, at any time during treatment. In a 'real-life' setting, clinical diagnosis of suspected abacavir hypersensitivity reaction in allele non-carriers remains crucial for further clinical decision making. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 1744-6880 1744-6880 |
| DOI: | 10.1097/FPC.0000000000000409 |