2009-07-20
(WASHINGTON) – From the start of the HIV epidemic, it
appeared that some of the people who were infected with the virus were
able to ward off the fatal effects of the disease longer than others.
Recent studies have begun to unravel the cause of this phenomenon, and
new research suggests that African Americans with the disease have a
unique survival advantage if they have both a low white blood cell
count (known as leukopenia) and a genetic variation that is found
mainly in persons of African ancestry. This study was prepublished online on July 20, 2009, in Blood, the official journal of the American Society of Hematology.
The research showed that African Americans with HIV who possess both
a variation in the gene for the Duffy antigen receptor for chemokine
(DARC) and leukopenia have slower HIV-to-AIDS progression rates than
HIV-infected European Americans with leukopenia. Previous studies
showed that the same DARC variant conferred protection for persons of
African ancestry against a particular form of malaria, and that persons
of African descent have, on average, lower white blood cell (WBC)
counts than persons of European ancestry. Leukopenia is one of several
blood conditions observed frequently in patients with HIV-1 infection,
but its impact on disease course is relatively unknown.
“Even though leukopenia is tied to both African ancestry and faster
disease progression, we found that compared with European Americans,
African American patients with HIV who have leukopenia do not
necessarily experience this expected outcome,” said lead author Sunil
Ahuja, MD, of the Veterans Administration (VA) Research Center for AIDS
and HIV-1 Infection and the University of Texas Health Science Center
in San Antonio.
This study evaluated data from the Air Force subset of the U.S.
Military’s HIV Natural History Study and included genetic and clinical
data from 1,132 participants. The researchers tested for the presence
of the DARC variation and evaluated patients’ WBC counts from diagnosis
and throughout the course of the disease to determine the impact of
different levels of WBC counts on survival rates. The prevalence of
leukopenia at the time of diagnosis was significantly higher in African
Americans (28 percent) than in European Americans (15 percent) or other
ethnicities (13 percent). The average WBC counts were also
significantly lower during the course of the disease in African
Americans with HIV than in other ethnicities.
The researchers found that leukopenia was generally associated with
a faster disease progression from HIV to AIDS, independent of known
predictors of AIDS development. “On average, leukopenic European
Americans progressed nearly three times faster than their
non-leukopenic African or European counterparts,” explained Hemant
Kulkarni, MD, first author of this study. “However, leukopenic African
Americans had a slower disease course than leukopenic European
Americans, even though twice as many African Americans in the study had
leukopenia.”
The investigators found that the DARC variation, not race, explained
the differences in WBC counts in African Americans with HIV. Among
those who were leukopenic, only those with the DARC variation
experienced a significant survival benefit. Additionally, this survival
advantage became increasingly pronounced in those with progressively
lower WBC counts, suggesting that the interaction between DARC and WBC
counts was the primary influence on slowing HIV disease progression in
African Americans.
“The results of this collaborative study highlight the importance of
accounting for other factors, such as the white blood cell count, to
uncover the full effects of genetic variations that may influence HIV
disease course,” said Capt. Gregory Martin, MD, United States Navy,
program director for the Infectious Diseases Clinical Research Program
(IDCRP) and an expert on infectious diseases who was not involved with
the study.
“White blood cells are intricately linked to inflammation, and
inflammation is known to fuel HIV disease progression. Thus, future
studies will need to decipher whether the interaction between the DARC
variant and low white blood cell counts results in a reduced
inflammatory state,” said Vincent Marconi, MD, of the IDCRP.
The U.S. Centers for Disease Control estimates that about 1 million
people in the United States are living with HIV or AIDS, and that about
60,000 individuals are infected with HIV each year.
The study represents a collaboration between investigators at the
IDCRP at the Uniformed Services University of the Health Sciences,
Bethesda, MD, the VA, and the University of Texas Health Science Center
at San Antonio. The study was funded by the National Institutes of
Health and the VA.
Reporters who wish to receive a copy of the study or arrange an interview with the investigators may contact Patrick C. Irelan at 202-776-0544 or pirelan@hematology.org.
The American Society of Hematology (www.hematology.org)
is the world’s largest professional society concerned with the causes
and treatment of blood disorders. Its mission is to further the
understanding, diagnosis, treatment, and prevention of disorders
affecting blood, bone marrow, and the immunologic, hemostatic, and
vascular systems, by promoting research, clinical care, education,
training, and advocacy in hematology. Last year, ASH launched Blood: The Vital Connection (www.bloodthevitalconnection.org),
a credible online resource addressing bleeding and clotting disorders,
anemia, and cancer. It provides hematologist-approved information about
these common blood conditions including risk factors, preventive
measures, and treatment options.
Blood, the official journal of ASH, is the most cited peer-reviewed publication in the field. Blood is issued to Society members and other subscribers weekly and is available in print and online at www.bloodjournal.org.
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