The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry

Hemant Kulkarni, Vincent C. Marconi, Weijing He, Michael L. Landrum, Jason F. Okulicz, Judith Delmar, Dickran Kazandjian, John Castiblanco, Seema S Ahuja, Edwina J. Wright, Robin A. Weiss, Robert A Clark, Matthew J. Dolan, Sunil K Ahuja

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Persons of African ancestry, on average, have lower white blood cell (WBC) counts than those of European descent (ethnic leukopenia), but whether this impacts negatively on HIV-1 disease course remains unknown. Here, in a large natural history cohort of HIV-infected subjects, we show that, although leukopenia (< 4000 WBC/mm3 during infection) was associated with an accelerated HIV disease course, this effect was more prominent in leukopenic subjects of European than African ancestry. The African-specific -46 C/C genotype of Duffy Antigen Receptor for Chemokines (DARC) confers the malaria-resisting, Duffy-null phenotype, and we found that the recently described association of this genotype with ethnic leukopenia extends to HIV-infected African Americans (AAs). The association of Duffy-null status with HIV disease course differed according to WBC but not CD4+ T-cell counts, such that leukopenic but not nonleukopenic HIV+ AAs with DARC -46C/C had a survival advantage compared with all Duffy-positive subjects. This survival advantage became increasingly pronounced in those with progressively lower WBC counts. These data highlight that the interaction between DARC genotype and the cellular milieu defined by WBC counts may influence HIV disease course, and this may provide a partial explanation of why ethnic leukopenia remains benign in HIV-infected AAs, despite immunodeficiency.

Original languageEnglish (US)
Pages (from-to)2783-2792
Number of pages10
JournalBlood
Volume114
Issue number13
DOIs
StatePublished - 2009

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Blood
Antigen Receptors
HIV
Leukopenia
Survival
Leukocyte Count
African Americans
Chemokines
Genotype
C Chemokines
T-cells
Leukocytes
CD4 Lymphocyte Count
Cells
Natural History
Malaria
HIV-1
T-Lymphocytes
Phenotype
Infection

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry. / Kulkarni, Hemant; Marconi, Vincent C.; He, Weijing; Landrum, Michael L.; Okulicz, Jason F.; Delmar, Judith; Kazandjian, Dickran; Castiblanco, John; Ahuja, Seema S; Wright, Edwina J.; Weiss, Robin A.; Clark, Robert A; Dolan, Matthew J.; Ahuja, Sunil K.

In: Blood, Vol. 114, No. 13, 2009, p. 2783-2792.

Research output: Contribution to journalArticle

Kulkarni, H, Marconi, VC, He, W, Landrum, ML, Okulicz, JF, Delmar, J, Kazandjian, D, Castiblanco, J, Ahuja, SS, Wright, EJ, Weiss, RA, Clark, RA, Dolan, MJ & Ahuja, SK 2009, 'The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry', Blood, vol. 114, no. 13, pp. 2783-2792. https://doi.org/10.1182/blood-2009-04-215186
Kulkarni, Hemant ; Marconi, Vincent C. ; He, Weijing ; Landrum, Michael L. ; Okulicz, Jason F. ; Delmar, Judith ; Kazandjian, Dickran ; Castiblanco, John ; Ahuja, Seema S ; Wright, Edwina J. ; Weiss, Robin A. ; Clark, Robert A ; Dolan, Matthew J. ; Ahuja, Sunil K. / The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry. In: Blood. 2009 ; Vol. 114, No. 13. pp. 2783-2792.
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abstract = "Persons of African ancestry, on average, have lower white blood cell (WBC) counts than those of European descent (ethnic leukopenia), but whether this impacts negatively on HIV-1 disease course remains unknown. Here, in a large natural history cohort of HIV-infected subjects, we show that, although leukopenia (< 4000 WBC/mm3 during infection) was associated with an accelerated HIV disease course, this effect was more prominent in leukopenic subjects of European than African ancestry. The African-specific -46 C/C genotype of Duffy Antigen Receptor for Chemokines (DARC) confers the malaria-resisting, Duffy-null phenotype, and we found that the recently described association of this genotype with ethnic leukopenia extends to HIV-infected African Americans (AAs). The association of Duffy-null status with HIV disease course differed according to WBC but not CD4+ T-cell counts, such that leukopenic but not nonleukopenic HIV+ AAs with DARC -46C/C had a survival advantage compared with all Duffy-positive subjects. This survival advantage became increasingly pronounced in those with progressively lower WBC counts. These data highlight that the interaction between DARC genotype and the cellular milieu defined by WBC counts may influence HIV disease course, and this may provide a partial explanation of why ethnic leukopenia remains benign in HIV-infected AAs, despite immunodeficiency.",
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