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Duke University has received a two-year, $3 million grant
from the Bill & Melinda Gates Foundation to study
resistance to HIV infection among people with hemophilia.

The study, to be conducted at the Center for Human Genome
Variation at Duke's Institute for Genome Sciences & Policy,
will build upon a growing body of evidence that may help
explain why some people are able to fend off infection, even
when repeatedly exposed to HIV, a phenomenon known as host
resistance. Center Director David Goldstein, PhD, will lead the
investigation in collaboration with Kevin Shianna, PhD, and
Jacques Fellay, MD, PhD.

Host resistance is present only in a small percentage of the
general population. It can be traced, in part, to the presence
of genetic variants linked to the ability to block
infection.

"But these known variants explain only a very small amount
of the differences among individuals exposed to the HIV virus,"
says Goldstein. "We think there are probably other, much rarer
variants that also play a role. We just haven't had the right
tools to find them, but now we do."

Goldstein says rare variants are more likely to be found in
a narrow population where people share unique or extreme
characteristics - like patients with hemophilia who have been
heavily exposed to HIV-contaminated blood products. Hemophilia
patients were often exposed to HIV-infected blood products in
the 1970s and 1980s before safety measures were undertaken to
screen out tainted blood. While most of these patients became
infected and died of AIDS, a significant minority did not.

"Interestingly, previous studies have shown that such
individuals are 15 times more likely to carry a specific
genetic variant linked to resistance (a deletion in the HIV
main co-receptor CCR5) than is a person in the general
population," added Goldstein. "That enrichment for a known
protective genetic factor tells us that HIV-exposed yet
uninfected individuals with hemophilia form an ideal study
group."

The support from the Gates Foundation will enable Goldstein,
Shianna and Fellay to use high-throughput sequencing technology
to resequence the genome of 50 individuals with hemophilia. The
study group, assembled by researchers in Duke's Center for
HIV/AIDS Vaccine Immunology (CHAVI), is composed of individuals
with a documented history of treatment with contaminated factor
VIII concentrate between 1979 and 1984, but who did not
contract HIV.

The goal is to discover rare variants enriched in the genome
of these carefully selected individuals. Researchers hope that
will enable them to identify which variants are most likely
associated with resistance to HIV infection.

"We hope this project will yield new information that will
help us to further understand disease resistance and to
identify new targets and guidance for drug and vaccine
development," says Goldstein. "Rare human genetic variation is
a new frontier for discovery and I am grateful to the Bill
& Melinda Gates Foundation for enabling us to develop it
here at Duke."