Duke University Receives Grant To Study HIV Resistance

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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, M.D., 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."

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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."

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