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Blood, 24 September 2009, Vol. 114, No. 13, pp. 2783-2792. Prepublished online as a Blood First Edition Paper on July 20, 2009; DOI 10.1182/blood-2009-04-215186. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2009-04-215186v1 114/13/2783    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Kulkarni, H. Articles by Ahuja, S. K. PubMed PubMed Citation Articles by Kulkarni, H. Articles by Ahuja, S. K. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 7, 2009 Accepted May 18, 2009 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, and Sunil K. Ahuja* Veterans Administration Research Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System, San Antonio, TX, United States Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, United States Department of Medicine, University of Texas Health Science Center, San Antonio, TX, United States Infectious Disease Service, San Antonio Military Medical Center (SAMMC), Brooke Army Medical Center (BAMC), Fort Sam Houston, TX, United States Department of Medicine, Wilford Hall Medical Center, Lackland AFB, TX, United States The Alfred Hospital, The Burnet Institute, and Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia Division of Infection and Immunity, University College London, London, United Kingdom Henry M. Jackson Foundation, Wilford Hall United States Air Force Medical Center, Lackland AFB, TX, United States Departments of Microbiology and Immunology, and Biochemistry, University of Texas Health Science Center, San Antonio, TX, United States * Corresponding author; email: ahujas{at}uthscsa.edu. 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 (<4,000 WBCs/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 -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 (AA). 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 non-leukopenic 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 African Americans, despite immunodeficiency. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: HIV: getting to the heart of DARCness Robert J. B. Nibbs Blood 2009 114: 2570-2571. [Full Text] [PDF] This article has been cited by other articles: R. J. B. Nibbs HIV: getting to the heart of DARCness Blood, September 24, 2009; 114(13): 2570 - 2571. [Full Text] [PDF]

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