期刊
CLINICAL INFECTIOUS DISEASES
卷 52, 期 10, 页码 1248-1256出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/cir119
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资金
- National Institute of Allergy and Infectious Disease, National Institutes of Health (NIH) [U19 AI 51794]
- CAPRISA training fellowship
- Fogarty AITRP fellowship [TWO-0023]
- KwaZulu-Natal Research Institute for TB and HIV (K-RITH)
- Hasso Plattner Foundation
- VA HIV/AIDS Center of the South Texas Veterans Health Care System [R37046326]
- Doris Duke Distinguished Clinical Scientist Award
- VA MERIT award
- Burroughs Wellcome Clinical Scientist Award in Translational Research
- K-RITH
- MRC [G0801176, G8712499] Funding Source: UKRI
- Medical Research Council [G8712499, G0801176] Funding Source: researchfish
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 similar to 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 x 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 similar to 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.
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