title: Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.
abstract: BACKGROUND
  Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols.
  
  
  METHODS
  Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n = 786) regimens in ACTG protocols 384, A5142, A5095, and A5202.
  
  
  RESULTS
  Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P < 5 × 10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition.
  
  
  CONCLUSIONS
  No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.
authors.affiliation: aBrandeis University, Waltham bCenter for Biostatistics in AIDS Research, Harvard School of Public Health cDepartment of Medicine, Harvard Medical School, Boston, Massachusetts dLos Angeles Biomed Research Institute at Harbor-UCLA Medical Center, Torrance eDepartment of Medicine and Center for AIDS Research, University of California San Diego, San Diego, California fWeill Cornell Medical College, New York, New York gDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA hDepartments of Medical Genetics and Epidemiology, University Medical Center Utrecht, Utrecht, The Netherlands iSchool of Life Sciences, The Swiss Institute of Technology jInstitute of Microbiology University Hospital, University of Lausanne, Lausanne, Switzerland.
authors.forename: David S
authors.initials: DS
authors.lastname: Lehmann
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
authors.forename: Richard H
authors.initials: RH
authors.lastname: Haubrich
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McLaren
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000008:administration & dosage*; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D000099227:Abacavir
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D000099227:Abacavir; C098320:efavirenz