Journal Article

Duffy-Null–Associated Low Neutrophil Counts Influence HIV-1 Susceptibility in High-Risk South African Black Women

Veron Ramsuran, Hemant Kulkarni, Weijing He, Koleka Mlisana, Edwina J. Wright, Lise Werner, John Castiblanco, Rahul Dhanda, Tuan Le, Matthew J. Dolan, Weihua Guan, Robin A. Weiss, Robert A. Clark, Salim S. Abdool Karim, Sunil K. Ahuja and Thumbi Ndung'u

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 52, issue 10, pages 1248-1256
Published in print May 2011 | ISSN: 1058-4838
Published online May 2011 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1093/cid/cir119
Duffy-Null–Associated Low Neutrophil Counts Influence HIV-1 Susceptibility in High-Risk South African Black Women

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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. Preseroconversion 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 preseroconversion neutrophil counts of <2500 cells/mm3 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/mm3. 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.

Journal Article.  5118 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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