The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry.
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/mm(3) 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 -46C/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.
Kulkarni
Hemant
H
Veterans Administration Research Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System, San Antonio, USA.
Marconi
Vincent C
VC
He
Weijing
W
Landrum
Michael L
ML
Okulicz
Jason F
JF
Delmar
Judith
J
Kazandjian
Dickran
D
Castiblanco
John
J
Ahuja
Seema S
SS
Wright
Edwina J
EJ
Weiss
Robin A
RA
Clark
Robert A
RA
Dolan
Matthew J
MJ
Ahuja
Sunil K
SK
D044383:Black People / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D004375:Duffy Blood-Group System / Q000235:genetics*; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000401:mortality*; D015528:HIV Seroprevalence; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count; D007970:Leukopenia / Q000208:ethnology / Q000209:etiology / Q000235:genetics* / Q000401:mortality*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics*; D016019:Survival Analysis; D001741:Black or African American
C473745:ACKR1 protein, human; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface