title: Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women.
abstract: BACKGROUND
  The Duffy-null trait and ethnic netropenia are both highly prevalent in Africa. The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)-1 infection among Africans is unknown.
  
  
  METHODS
  The triangular relationship among pre-seroconversion PBC counts, host genotypes, and risk of HIV acquisition was determined in a prospective cohort of black South African high-risk female sex workers. Twenty-seven women had seroconversion during follow-up, and 115 remained HIV negative for 2 years, despite engaging in high-risk activity.
  
  
  RESULTS
  Pre-seroconversion neutrophil counts in women who subsequently had seroconversion were significantly lower, whereas platelet counts were higher, compared with those who remained HIV negative. Comprising 27% of the cohort, subjects with pre-seroconversion neutrophil counts of <2500 cells/mm(3) had a ∼3-fold greater risk of acquiring HIV infection. In a genome-wide association analyses, an African-specific polymorphism (rs2814778) in the promoter of Duffy Antigen Receptor for Chemokines (DARC -46T > C) was significantly associated with neutrophil counts (P = 7.9 × 10(-11)). DARC -46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and in our cohort, only subjects with this genotype had pre-seroconversion neutrophil counts of <2500 cells/mm(3). The risk of acquiring HIV infection was ∼3-fold greater in those with the trait of Duffy-null-associated low neutrophil counts, compared with all other study participants.
  
  
  CONCLUSIONS
  Pre-seroconversion neutrophil and platelet counts influence risk of HIV infection. The trait of Duffy-null-associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Veron
authors.initials: V
authors.lastname: Ramsuran
authors.forename: Hemant
authors.initials: H
authors.lastname: Kulkarni
authors.forename: Weijing
authors.initials: W
authors.lastname: He
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.forename: Edwina J
authors.initials: EJ
authors.lastname: Wright
authors.forename: Lise
authors.initials: L
authors.lastname: Werner
authors.forename: John
authors.initials: J
authors.lastname: Castiblanco
authors.forename: Rahul
authors.initials: R
authors.lastname: Dhanda
authors.forename: Tuan
authors.initials: T
authors.lastname: Le
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dolan
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.forename: Robin A
authors.initials: RA
authors.lastname: Weiss
authors.forename: Robert A
authors.initials: RA
authors.lastname: Clark
authors.forename: Salim S Abdool
authors.initials: SS
authors.lastname: Karim
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Ahuja
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
mesh_terms: D015331:Cohort Studies; D004375:Duffy Blood-Group System / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006678:HIV / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009503:Neutropenia / Q000276:immunology*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013019:South Africa
chemical_list: C473745:ACKR1 protein, human; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface