Abacavir, abacavir hypersensitivity in patients with HLA-B 5701 (Hypersensitivity to abacavir In Patients With haplotype HLA-B 5701).
Abacavir is a reverse transcriptase inhibitor preferentially used in therapy for infection HIV (HIV). In most cases use proceeds without complications significance, but a significant percentage of patients (5-12%) has detected a hypersensitivity reaction to abacavir as adversely administration effect, which limits their use in antiretroviral therapy and requires a high degree of clinical surveillance. In cases of hypersensitivity, there could be an increase in their toxicity profile, consisting of an increased risk of myocardial infarction, according to the Spanish Agency for Medicines and Health Products (AEMPS).
The hypersensitivity reaction generally occurs within the first 6 weeks of abacavir and is characterized by the appearance of rash and fever, gastrointestinal symptoms (nausea, vomiting, diarrhea and abdominal pain), dyspnoea, myalgia, musculoskeletal pain, headache, etc. These symptoms worsen if further treatment and usually cease if interrupt. The problem is that the symptoms of hypersensitivity reaction to abacavir are unspecific and can be difficult to distinguish from infections or reactions to other drugs commonly empleodas for HIV therapy, which can lead to misdiagnosis if they have carried out only by clinical manifestations.
The development of hypersensitivity is related to some MHC proteins (Major Histocompatibility Complex), encoded by a closely linked and highly polymorphic genes, i.e., genes with a large number of allelic variants at each locus. For hypersensitivity reactions to abacavir it has been determined that HLA-B * 5701 can predict the risk significantly abacavir hypersensitivity.
The HLA-B gene, located on the short arm of chromosome 6 (6p21.3), encodes a protein that plays a critical role in the immune system. HLA-B is part of a gene family of human leukocyte antigen complex (HLA). The HLA complex helps the immune system to distinguish proteins body's own proteins encoded by foreign invaders such as viruses and bacteria. HLA is the human version of the major histocompatibility complex (MHC), a family of genes that occurs in many species and involved in antigen presentation to immune cells, as well as antigenic compatibility between individuas. Genes in this complex are classified into three basic groups: Class I, Class II and Class III. In humans, the HLA-B gene and two related genes, HLA-A and HLA-C genes are major MHC class I.
The molecular biology methods developed for the detection of HLA-B * 5701 allow us a prediction or confirmation of the clinical diagnosis without reintroducing the drug in the patient, thereby avoiding all possible problems associated with their hypersensitivity. In this way, which patients should not receive treatment with abacavir even prior to its administration form it could be determined.
Tests in IVAMI: in IVAMI perform detection HLA-B * 5701, using the complete PCR amplification and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).