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Through the new consortium, led by scientists at Duke University, investigators who once competed to unravel the mysteries of HIV will share access to patient groups, called cohorts, they have studied.
Support for the consortium is provided by the Center for HIV/AIDS Vaccine Immunology (CHAVI), established at Duke in 2005 with a grant that could total as much as $300 million over seven years from the U.S. National Institute of Allergy and Infectious Diseases. CHAVI's initial mission is to find out what the immune system does during HIV infection -- including in the rare individuals who control the infection on their own -- and try to produce a vaccine to mimic those responses.
"We intend to use natural genetic differences among people to point the way toward the most promising avenues for vaccine development," said David Goldstein, Ph.D., director of the Center for Population Genomics and Pharmacogenetics at the Duke Institute for Genome Sciences & Policy and director of CHAVI's host genetics research core. "We want to find out why some people naturally hold the virus down to almost undetectable levels while others lose control of it quickly."
The newly organized group, called EuroCHAVI, will recruit 600 patients from nine cohorts. "This will be is the largest cohort assembled for large-scale analysis of genetic differences among HIV-infected patients," said Amalio Telenti, M.D., Ph.D., a key organizer of the collaboration. Telenti is professor of medical virology and co-director of the Institute of Microbiology at the University of Lausanne, Switzerland.
EuroCHAVI aims to quickly identify common genes -- wherever they are in the human genome -- that affect how the body responds to HIV. "Because of the willingness of researchers throughout the world to work together, the prospects are very real for getting answers by next year," Goldstein said.
"This is exactly the kind of work we are trying to catalyze," said CHAVI director Barton Haynes, M.D. Haynes is a professor of medicine and director of the Human Vaccine Institute at Duke University Medical Center.
Despite repeated exposures, some people apparently never become infected with HIV. Among those who become infected, there is dramatic variation in how the body responds to HIV and in how long it takes for infection to progress to AIDS. EuroCHAVI scientists will try to understand these differences by searching for an underlying genetic influence.
Typically, scientists use genetic analysis to search for minor changes in the sequence of 3 billion DNA letters that make up the human genome. The changes, called single nucleotide polymorphisms (SNPs), are like single-letter variations in the spellings of a word. The SNPs cluster in local neighborhoods, known as haplotypes, within the genome. Most of these variations are biologically meaningless, but a small fraction can alter the function of a gene. Combining the effect of many slightly altered genes may significantly increase the risk of disease -- in this case, HIV/AIDS.
The genome studies will be carried out at the Duke Institute for Genome Sciences & Policy and the University of Lausanne. "Large-scale genome analyses like this are critical for determining the role of the genome in complex diseases such as AIDS," said Huntington Willard, Ph.D., director of the Duke genomics institute. The combination of large population cohorts and state-of-the-art genome technology will allow us to dissect the genetic factors that contribute to disease."
CHAVI also will establish an even larger cohort of HIV-infected patients in Africa and perform the same genetic analyses. Haplotypes, or genetic neighborhoods, are poorly known for people of African ancestry, Goldstein said. CHAVI will fund investigators to develop a detailed and accurate map of haplotypes among these populations.
EuroCHAVI collaborators include the Swiss HIV cohort; the IRSICaixa study and the Clinic Hospital cohort in Spain; the Danish HIV cohort; the Perth-Western Australia cohort; the Modena cohort and the San Raffaele Scientific Institute cohort in Italy; the German National Competence Network for HIV/AIDS; and the Guy's, King's College and St. Thomas' Hospitals study in the United Kingdom. The University of Geneva, the Swiss Federal Institute of Technology in Lausanne and the University of Ioannina in Greece will partner as analytical centers.
CHAVI is a consortium of scientists from Duke University, Harvard University, the University of Alabama at Birmingham, the University of North Carolina at Chapel Hill, and Oxford University in the United Kingdom.