PMID- 32453265
OWN - NLM
STAT- MEDLINE
DCOM- 20210308
LR  - 20210308
IS  - 1744-6880 (Electronic)
IS  - 1744-6872 (Linking)
VI  - 30
IP  - 8
DP  - 2020 Oct
TI  - Abacavir adverse reactions related with HLA-B*57: 01 haplotype in a large cohort 
      of patients infected with HIV.
PG  - 167-174
LID - 10.1097/FPC.0000000000000409 [doi]
AB  - OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
FAU - Quiros-Roldan, Eugenia
AU  - Quiros-Roldan E
AD  - Department of Infectious and Tropical Diseases, University of Brescia.
FAU - Gardini, Giulia
AU  - Gardini G
AD  - Department of Infectious and Tropical Diseases, University of Brescia.
FAU - Properzi, Martina
AU  - Properzi M
AD  - Department of Infectious and Tropical Diseases, University of Brescia.
FAU - Ferraresi, Alice
AU  - Ferraresi A
AD  - Department of Infectious and Tropical Diseases, University of Brescia.
FAU - Carella, Graziella
AU  - Carella G
AD  - Histocompatibility Laboratory, Department of Transfusion Medicine, ASST Spedali 
      Civili Hospital, Brescia, Italy.
FAU - Marchi, Alessandro
AU  - Marchi A
AD  - Department of Infectious and Tropical Diseases, University of Brescia.
FAU - Malagoli, Alberto
AU  - Malagoli A
AD  - Histocompatibility Laboratory, Department of Transfusion Medicine, ASST Spedali 
      Civili Hospital, Brescia, Italy.
FAU - Foca, Emanuele
AU  - Foca E
AD  - Department of Infectious and Tropical Diseases, University of Brescia.
FAU - Castelli, Francesco
AU  - Castelli F
AD  - Department of Infectious and Tropical Diseases, University of Brescia.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pharmacogenet Genomics
JT  - Pharmacogenetics and genomics
JID - 101231005
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Dideoxynucleosides)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*57:01 antigen)
RN  - WR2TIP26VS (abacavir)
SB  - IM
MH  - Adult
MH  - Anti-HIV Agents/administration & dosage/*adverse effects
MH  - Clinical Decision-Making
MH  - Dideoxynucleosides/administration & dosage/*adverse effects
MH  - Drug Hypersensitivity/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - HIV Infections/*drug therapy/genetics
MH  - HLA-B Antigens/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
EDAT- 2020/05/27 06:00
MHDA- 2021/03/09 06:00
CRDT- 2020/05/27 06:00
PHST- 2020/05/27 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
PHST- 2020/05/27 06:00 [entrez]
AID - 01213011-202010000-00001 [pii]
AID - 10.1097/FPC.0000000000000409 [doi]
PST - ppublish
SO  - Pharmacogenet Genomics. 2020 Oct;30(8):167-174. doi: 
      10.1097/FPC.0000000000000409.