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Autor(en) / Beteiligte

Titel

Comparison of methods for in-house screening of HLA-B57:01 to prevent abacavir hypersensitivity in HIV-1 care

Ist Teil von

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2015

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

Abacavir is a nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy in HIV-1-infected patients. Because this drug can cause a hypersensitivity reaction that is correlated with the presence of the HLA-B*57:01 allotype, screening for the presence of HLA-B*57:01 is recommended before abacavir initiation. Different genetic assays have been developed for HLA-B*57:01 screening, each with specific sensitivity, turnaround time and assay costs. Here, a new real-time PCR (qPCR) based analysis is described and compared to sequence specific primer PCR with capillary electrophoresis (SSP PCR CE) on 149 patient-derived samples, using sequence specific oligonucleotide hybridization combined with high resolution SSP PCR as gold standard. In addition to these PCR based methods, a complementary approach was developed using flow cytometry with an HLA-B17 specific monoclonal antibody as a pre-screening assay to diminish the number of samples for genetic testing. All three assays had a maximum sensitivity of >99. However, differences in specificity were recorded, i.e. 84.3%, 97.2% and >99% for flow cytometry, qPCR and SSP PCR CE respectively. Our data indicate that the most specific and sensitive of the compared methods is the SSP PCR CE. Flow cytometry pre-screening can substantially decrease the number of genetic tests for HLA-B*57:01 typing in a clinical setting.

Sprache: Englisch
Identifikatoren: ISSN: 1932-6203
eISSN: 1932-6203
DOI: 10.1371/journal.pone.0123525
Titel-ID: cdi_plos_journals_1673378865

Format: –
Schlagworte: Abacavir, Alleles, Allergic reaction, Allergy, Antiretroviral agents, Antiretroviral drugs, Antiretroviral Therapy, Highly Active, Antiviral agents, Assaying, Comparative analysis, Cost analysis, Dideoxynucleosides - administration & dosage, Dideoxynucleosides - adverse effects, DNA polymerases, DNA Primers - chemical synthesis, DNA Primers - genetics, Drug Hypersensitivity - etiology, Drug Hypersensitivity - genetics, Drug Hypersensitivity - immunology, Drug Hypersensitivity - prevention & control, Electrophoresis, Electrophoresis, Capillary, Flow Cytometry, Gene Expression, Genetic screening, Genetic Testing - methods, Highly active antiretroviral therapy, Histocompatibility antigens, HIV, HIV (Viruses), HIV Infections - drug therapy, HIV Infections - genetics, HIV Infections - immunology, HIV Infections - virology, HIV-1 - drug effects, HIV-1 - enzymology, HIV-1 - genetics, HLA antigens, HLA histocompatibility antigens, HLA-B Antigens - genetics, HLA-B Antigens - immunology, Human immunodeficiency virus, Humans, Hybridization, Hypersensitivity, Medical screening, Methods, Monoclonal antibodies, Nucleic Acid Hybridization - methods, Oligonucleotides, Real-Time Polymerase Chain Reaction - methods, Reverse Transcriptase Inhibitors - administration & dosage, Reverse Transcriptase Inhibitors - adverse effects, Sensitivity, Sensitivity and Specificity, Zeidae

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