title: Association of the HLA-B*53:01 Allele With Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome During Treatment of HIV Infection With Raltegravir.
abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, severe adverse event during treatment with raltegravir. The occurrence of DRESS syndrome during treatment with other drugs is strongly associated with particular HLA alleles.
  
  
  
  We performed HLA testing in 3 of the 5 patients previously reported to have developed raltegravir-induced DRESS syndrome and in 1 previously unreported patient. We then used virtual modeling to visualize interactions between raltegravir and the imputed HLA molecule.
  
  
  
  Five of the 6 patients who developed raltegravir-induced DRESS syndrome were African, and 1 was Hispanic. HLA typing was performed in 4 patients, all of whom carried both the HLA-B*53 allele and the HLA-C*04 allele to which it is commonly haplotypic. No other HLA alleles were shared by all of the tested patients. Given the approximate prevalence of HLA-B*53 carriage in African (20%) and Hispanic (6%) populations, the probability of all 4 patients being HLA-B*53 carriers, and 2 of 3 African patients being homozygous for HLA-B*53:01, is approximately 0.00002.
  
  
  
  These data implicate the prevalent African allele HLA-B*53:01 in the immunopathogenesis of raltegravir-induced DRESS syndrome. Although the immunopathogenic mechanisms are currently unknown, virtual modeling suggests that raltegravir may bind within the antigen binding cleft of the HLA-B*53:01 molecule, but not within the closely related HLA-B*35:01 molecule. Further studies are necessary to confirm the strength of the association between carriage of the HLA-B*53:01 allele and raltegravir-induced DRESS syndrome, and the potential utility of HLA screening before raltegravir treatment.
authors.affiliation: Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.|Infectious Diseases Department, Auckland City Hospital, New Zealand.
authors.forename: Mark
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Infectious Diseases Department, Auckland City Hospital, New Zealand.
authors.forename: Chris
authors.initials: C
authors.lastname: Hopkins
authors.affiliation: Infectious Diseases Department, Auckland City Hospital, New Zealand.
authors.forename: Eamon
authors.initials: E
authors.lastname: Duffy
authors.affiliation: Department of Internal Medicine, University of California San Diego, California, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lee
authors.affiliation: Centre d'Investigation Clinique Cochin-Pasteur de Vaccinologie Cochin-Pasteur, Hôpital Cochin, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Loulergue
authors.affiliation: Department of Infectious Diseases, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ripamonti
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Ostrov
authors.affiliation: Department of Pharmacology, Oates Institute for Experimental Therapeutics, Vanderbilt University Medical School, Nashville, Tennessee, USA.|Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.|Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D063926:Drug Hypersensitivity Syndrome / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D000068898:Raltegravir Potassium / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D006680:HLA Antigens; C078438:HLA-B53 antigen; D000068898:Raltegravir Potassium
keywords: DRESS syndrome; HLA_B*53:01; raltegravir