TY - JOUR
T1 - The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry
AU - Kulkarni, Hemant
AU - Marconi, Vincent C.
AU - He, Weijing
AU - Landrum, Michael L.
AU - Okulicz, Jason F.
AU - Delmar, Judith
AU - Kazandjian, Dickran
AU - Castiblanco, John
AU - Ahuja, Seema S.
AU - Wright, Edwina J.
AU - Weiss, Robin A.
AU - Clark, Robert A.
AU - Dolan, Matthew J.
AU - Ahuja, Sunil K.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70350495370&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-04-215186
DO - 10.1182/blood-2009-04-215186
M3 - Article
C2 - 19620399
AN - SCOPUS:70350495370
SN - 0006-4971
VL - 114
SP - 2783
EP - 2792
JO - Blood
JF - Blood
IS - 13
ER -