The first genome-wide association study of an infectious disease, conducted by an international group of researchers through the Center for HIV/AIDS Vaccine Immunology (CHAVI), has yielded a new understanding of why some people can suppress virus levels following HIV infection.
"The clearer picture of host responses to the virus achieved through this examination of genomes could lead to improved HIV therapies and provides new targets for vaccine developers," says Elias A. Zerhouni, M.D., director of the National Institutes of Health (NIH). CHAVI, which is led by Barton Haynes, M.D., of Duke University, Durham, N.C., was established in 2005 by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH.
CHAVI's host genetics team, led by David Goldstein, Ph.D., also of Duke University, included scientists from several European countries and Australia who formed a consortium, EuroCHAVI, to perform this study. The investigators identified three gene variants, two of which are linked to an infected person's ability to control HIV viral load and a third that is implicated in disease progression to AIDS. The research is being published by Science on the Science Express Web site on Thursday, July 19.
"CHAVI is designed to foster collaborative research to overcome roadblocks that have impeded HIV vaccine development," says NIAID Director Anthony S. Fauci, M.D. "The insights into genetic factors influencing host control of HIV revealed by this work exemplify the power of such collective investigations."
Genome-wide association studies aim to identify genetic variations among people that can be tied to variations in disease susceptibility. Recent genome-wide association studies have found genetic markers linked to increased risk of such ailments as diabetes, cancer and heart disease. The CHAVI investigators are the first to apply genome-wide association techniques to an infectious disease.
"People vary greatly in their vulnerability to HIV infection," notes Dr. Haynes. "In particular, there are striking and largely unexplained differences between individuals in the degree to which they are able to hold viral levels to a low set point in the period soon after infection." If scientists could pinpoint the gene variants that help some people control HIV infection--or avoid it altogether--they might be able to rationally design therapies or vaccines to mimic these naturally occurring genetic advantages, he notes.
In 2006, CHAVI researchers launched an effort to pool genetic data from HIV-positive individuals who had enrolled in nine studies based throughout Europe and in Australia. Together, these studies contained information on more than 30,000 individuals. From this pooled cohort, the CHAVI scientists ultimately chose 486 DNA samples--representing the genomes of 486 HIV-positive people whose viral load set points had been carefully and accurately measured at multiple time points--for the genome-wide association study.