title: Chemokine (C-C motif) receptor 5 -2459 genotype in patients receiving highly active antiretroviral therapy: race-specific influence on virologic success.
abstract: BACKGROUND
  In patients receiving highly active antiretroviral therapy (HAART), antiretroviral drug-metabolizing enzyme and transporter gene polymorphisms, as well as chemokine receptor gene polymorphisms, may influence response to treatment.
  
  
  METHODS
  In a North American, treated, adherent human immunodeficiency virus (HIV)-positive cohort (self-identified whites, n = 175; blacks, n = 218), we investigated whether CYP2B6 (516G>T, 983T>C), UGT2B7 (IVS1+985A>G, 802C>T), MDR1 3435C>T, chemokine (C-C motif) receptor 2 (CCR2) 190G>A, and CCR5 (-2459G>A, Δ32) polymorphisms influenced the time to achieve virologic success (TVLS).
  
  
  RESULTS
  No difference in TVLS was observed between races. In Kaplan-Meier analyses, only 516G>T (log-rank P = .045 for comparison of GG, GT, and TT and P = .02 GG + GT vs TT) and -2459G>A (log-rank P = .04 for GG, GA, and AA and P = .02 for GG + GA vs AA) genotypes were significantly associated with TVLS in black patients but not in white patients. However, in the Cox proportional hazards model that included age, sex, baseline CD4(+) T cell count, and baseline viral load, no significant association was observed between 516G>T and TVLS, whereas the association between -2459G>A and TVLS remained significant even after including CCR2 190G>A as well as all the drug-metabolizing enzyme and transporter genotypes.
  
  
  CONCLUSIONS
  These findings suggest that CCR5 -2459G>A genotype had a strong, race-specific influence on TVLS in this cohort. Understanding the possible mechanisms underlying this influence requires further studies.
authors.affiliation: Center for Global Health and Diseases and Diseases, Wolstein Research Bldg, Room 4204, 2103 Cornell Rd, Cleveland, OH 44106-7286, USA. rkm@case.edu
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Mehlotra
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Cheruvu
authors.forename: Melinda J
authors.initials: MJ
authors.lastname: Blood Zikursh
authors.forename: Rebekah L
authors.initials: RL
authors.lastname: Benish
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Salata
authors.forename: Barbara
authors.initials: B
authors.lastname: Gripshover
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.forename: Michelle V
authors.initials: MV
authors.lastname: Lisgaris
authors.forename: Scott
authors.initials: S
authors.lastname: Fulton
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Subauste
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jurevic
authors.forename: Chantal
authors.initials: C
authors.lastname: Guillemette
authors.forename: Peter A
authors.initials: PA
authors.lastname: Zimmerman
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D044383:Black People; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019713:Receptors, CCR5 / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D044465:White People
chemical_list: D019713:Receptors, CCR5