Mass. General Hospital receives Gates Foundation grant to expand HIV controllers study

March 04, 2008

The Massachusetts General Hospital (MGH) has received a five-year, $20.5 million grant from the Bill & Melinda Gates Foundation to expand an international program investigating the biological factors underlying immune system control of HIV, the virus that causes AIDS. The grant provides support to the International HIV Controllers Study, which currently involves researchers from more than a dozen countries and has the overall goal of discovering information that can guide design of a vaccine to limit viral replication in HIV-infected individuals. A primary focus will be understanding genetic and immunological factors that have allowed a few individuals to control HIV naturally without the need for medications, some for more than 25 years.

The grant is part of the Collaboration for AIDS Vaccine Discovery, an international network of research consortia funded by the Gates Foundation to address priorities in the Global HIV Vaccine Enterprise scientific plan.

"We believe that it is critical to understand how these individuals - who are maintaining viral levels so low that transmission and disease progression should decrease markedly - are keeping the virus in check and preventing it from causing disease," says Bruce Walker, MD, director of the Partners AIDS Research Center at MGH and principal investigator of the Gates Foundation grant. "By recruiting enough of these individuals, we hope to identify the genetic basis for this viral control, using novel methods developed for the Human Genome Project. We believe this approach is all the more important given recent setbacks in HIV vaccine trials."

For more than 15 years it has been apparent that a small minority of HIV-positive people remained healthy despite many years of infection. As techniques for measuring viral levels in the bloodstream became more sensitive, it was possible to identify this group of viremic controllers, who can maintain viral loads below 2,000 copies/ml, and an even smaller group of aviremic or 'elite' controllers, with viral loads less than 50 copies/ml. In 2006 Walker and his colleagues founded the HIV Controllers Study, with a $2.5 million grant from the Mark and Lisa Schwartz Foundation. Through national and international collaborations, they have already recruited nearly 1,000 controllers into the study.

With the new grant from the Gates Foundation, the team plans to expand the study group to 2,000 participants - 1,000 elite controllers and 1,000 viremic controllers - from around the world. The investigators will compare DNA from these individuals to genetic data from 3,000 people with progressive HIV infection, searching for genetic factors that may be associated with viremic control by sequencing 650,000 SNP (single nucleotide polymorphism) sites in each participant's genome. The project will also use the latest technology to analyze which immune responses best suppress viral replication and investigate how the virus evolves to escape the immune system, additional information that can contribute to vaccine strategies.

Potential participants in the study are HIV-positive adults aged 18 to 75, not currently on anti-HIV medication, who have maintained viral loads less than 2,000 copies/ml for at least one year. Participation involves having a single blood sample taken, which can be done by participants' local health care providers. Additional information about the study, including a list of participating institutions and more detailed instructions for enrolling and providing samples, is available at www.HIVcontrollers.org, by e-mailing elitecontrollerstudy@partners.org or calling 617 726-5536. All information gathered will be kept confidential.

"Since other approaches to vaccine development have not been successful, uncovering how some humans are able to coexist with the virus without developing AIDS, in spite of not receiving any therapies, is critical," says Steven Deeks, MD, of the University of California at San Francisco, a major collaborator on the International HIV Controllers Study.
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In addition to Walker, leaders of the Gates-funded project include Sylvie Le Gall, PhD, Marcus Altfeld, MD, PhD, and Todd Allen, PhD, of MGH-PARC; David Altshuler, MD, PhD, and Matthew Henn, PhD, Broad Institute of Harvard University and Massachusetts Institute of Technology; Paul de Bakker, PhD, Brigham and Women's Hospital; Thumbi Ndung'u, PhD, University of KwaZulu Natal, Durban, South Africa; Mary Carrington, PhD, U.S. National Cancer Institute; and Heiko Jessen, MD, Berlin, Germany. Along with Deeks, major collaborators on the International HIV Controllers Study include Martin Markowitz, MD, Rockefeller University; Douglas Richman, MD, University of California at San Diego; Amalio Telenti, MD, PhD, University of Lausanne, Switzerland; Matthew Dolan, MD, U.S. Defense Institute for Medical Operations; Jill Gilmour, PhD, International AIDS Vaccine Initiative; and additional scientists and health care providers from the US, Europe, and Australia.

The Partners AIDS Research Center was established in 1995 in response to the continuing world-wide AIDS pandemic. The center serves both Massachusetts General Hospital and Brigham and Women's Hospital, the founding members of Partners HealthCare, and is a natural progression of the more than 20-year commitment by the clinicians and scientists at those institutions to HIV and AIDS research and care. The center's scope has broadened further with the participation of the Dana Farber/Partners Cancer Center regarding AIDS oncology and close collaborative ties to Fenway Community Health Center and the Lemuel Shattuck Hospital.

Massachusetts General Hospital (www.massgeneral.org), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

Massachusetts General Hospital

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