{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T10:16:04Z","timestamp":1786529764039,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,11]],"date-time":"2018-12-11T00:00:00Z","timestamp":1544486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2019,1]]},"abstract":"Introduction<\/jats:title>Human leukocyte antigen (HLA)<\/jats:styled-content>\u2010B*5701 screening identifies patients at increased risk for abacavir (ABC<\/jats:styled-content>) hypersensitivity reaction (HSR<\/jats:styled-content>). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and human immunodeficiency virus treatment guidelines in 2008. Company meta\u2010analyses of trials pre\u2013HLA<\/jats:styled-content>\u2010B*5701 screening reported HSR<\/jats:styled-content> rates of 4\u20138%. We analyzed the effectiveness of HLA<\/jats:styled-content>\u2010B*5701 screening on reducing HSR<\/jats:styled-content> rates using clinical trial, Observational Pharmaco\u2010Epidemiology Research & Analysis (OPERA<\/jats:styled-content>) cohort, and spontaneous reporting data.<\/jats:p><\/jats:sec>Methods<\/jats:title>A meta\u2010analysis examined 12 trials in 3063 HLA<\/jats:styled-content>\u2010B*5701\u2013negative patients receiving an ABC<\/jats:styled-content>\u2010containing regimen from April 9, 2007, to September 22, 2015. Potential cases were identified using prespecified Medical Dictionary for Regulatory Activities (MedDRA<\/jats:styled-content>) preferred terms (drug hypersensitivity, hypersensitivity, anaphylactic reaction, anaphylaxis<\/jats:italic>) and adjudicated against a Company ABC HSR<\/jats:styled-content> case definition. Investigator\u2010diagnosed cases were identified and rates were calculated. In the OPERA<\/jats:styled-content> cohort, 9619 patients initiating their first ABC<\/jats:styled-content>\u2010containing regimen from January 1, 1999, to January 1, 2016, were identified. Patients were observed from regimen start until the earliest\u2010following censoring event: ABC<\/jats:styled-content> discontinuation, loss to follow\u2010up, death, or study end (July 31, 2016). OPERA<\/jats:styled-content> physicians evaluated events against OPERA<\/jats:styled-content> definitions for definite\/probable cases of ABC HSR<\/jats:styled-content>; rates were calculated pre\u2010 and post\u20102008. The Company case definition was used to identify spontaneously reported cases for four marketed ABC<\/jats:styled-content>\u2010containing products; reporting rates were calculated using estimated exposure from sales data, through December 31, 2016.<\/jats:p><\/jats:sec>Results<\/jats:title>Suspected ABC HSR<\/jats:styled-content> rates were 1.3% or less in the meta\u2010analysis. In the OPERA<\/jats:styled-content> cohort, the rate was 0.4% among patients initiating ABC<\/jats:styled-content> post\u20102008 versus 1.3% pre\u20102008 (p<0.0001). Spontaneous reporting rates were low post\u20102008 (54 to 22 cases per 100,000 patient\u2010years exposure [PYE<\/jats:styled-content>]) versus pre\u20102008 (618 to 55 cases per 100,000 PYE<\/jats:styled-content>).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Clinically suspected ABC HSR<\/jats:styled-content> rates were 1.3% or less in HLA<\/jats:styled-content>\u2010B*5701\u2013negative patients. Recognizing their limitations, data from the OPERA<\/jats:styled-content> cohort and spontaneous reporting indicate that HLA<\/jats:styled-content>\u2010B*5701 screening has reduced reporting rates of suspected HSR<\/jats:styled-content> in clinical practice. Where screening for HLA<\/jats:styled-content>\u2010B*5701 is standard care, patients should be confirmed negative for this allele before starting ABC<\/jats:styled-content> treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2196","type":"journal-article","created":{"date-parts":[[2018,11,10]],"date-time":"2018-11-10T05:03:55Z","timestamp":1541826235000},"page":"40-54","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA<\/scp>\u2010B*5701 Screening as a Risk\u2010Mitigation Measure"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8890-9918","authenticated-orcid":false,"given":"Chris M.","family":"Stainsby","sequence":"first","affiliation":[{"name":"Global Clinical Safety and Pharmacovigilance GlaxoSmithKline London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora M.","family":"Perger","sequence":"additional","affiliation":[{"name":"Safety and Pharmacovigilance ViiV Healthcare London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vani","family":"Vannappagari","sequence":"additional","affiliation":[{"name":"Epidemiology and Real World Evidence ViiV Healthcare Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karam C.","family":"Mounzer","sequence":"additional","affiliation":[{"name":"Infectious Diseases Philadelphia FIGHT Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky K.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Internal Medicine AIDS Healthcare Foundation New York New York"},{"name":"Internal Medicine NYU Langone Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassidy E.","family":"Henegar","sequence":"additional","affiliation":[{"name":"Epidemiology and Real World Evidence ViiV Healthcare Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Oyee","sequence":"additional","affiliation":[{"name":"Statistics, Programming and Data Strategy GlaxoSmithKline London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rimgaile","family":"Urbaityte","sequence":"additional","affiliation":[{"name":"Statistics, Programming and Data Strategy GlaxoSmithKline London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Lane","sequence":"additional","affiliation":[{"name":"Global Clinical Safety and Pharmacovigilance GlaxoSmithKline London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay M.","family":"Carter","sequence":"additional","affiliation":[{"name":"Global Medical Sciences ViiV Healthcare Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E.","family":"Pakes","sequence":"additional","affiliation":[{"name":"Global Medical Sciences ViiV Healthcare Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Shaefer","sequence":"additional","affiliation":[{"name":"Global Medical Sciences ViiV Healthcare Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku279"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(01)80132-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/339751"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(02)85132-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","unstructured":"ViiV Healthcare.Ziagen (abacavir) package insert. 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