Researchers seek to solve mystery of natural HIV control

In search of new vaccine strategies, study will examine genetics, immune systems of those able to suppress viral replication

An international, multi-institutional research consortium is seeking to discover how a few HIV-infected individuals are naturally able to suppress replication of the virus. The Elite Controller Collaborative Study (http://www.mgh.harvard.edu/aids/hiv_elite_controllers.asp), the first large-scale haplotype-mapping study in people infected with HIV, is searching for genetic factors that may explain these individuals' unique ability to control the virus without treatment, sometimes as long as 25 years after infection.

"If we could discover how these individuals can coexist with this virus without damage to their immune system and could find a way to replicate that ability in others, we would have a recipe for halting the HIV epidemic," says Bruce Walker, MD, director of Partners AIDS Research Center (PARC) at Massachusetts General Hospital and an initial organizer of the Elite Controller Collaborative Study. Walker discussed the project in a media briefing today at the 16th International AIDS Conference in Toronto.

Most people infected with HIV cannot control replication of the virus with their immune systems alone. Unless antiviral medications are used, the virus continues to reproduce until it overwhelms the CD4 T helper cells, suppressing the immune response and leading to AIDS. In the early 1990s, it was recognized that a small minority of HIV-positive people remained healthy and did not progress to AIDS despite many years of infection. The term "long-term nonprogressors" was used to refer to this group. With today's more sensitive techniques for measuring viral levels in the bloodstream, individuals who are able to maintain low levels of HIV replication can be identified soon after their infection is diagnosed. Some of these viremic controllers can maintain viral loads below 2,000 copies/ml, while an even smaller group, called elite controllers, have viral loads too low to be detected by currently available assays.

"The primary goal of the Elite Controller Collaborative Study is to identify the mechanism that explains control of viral replication in both of these groups, " says Florencia Pereyra, MD, of PARC, lead coordinator of the research team. "We want to use that knowledge to develop a first-generation HIV vaccine, which may not cure or prevent infection but could successfully suppress viral levels. Since this natural ability is so rare, we need to work with collaborators around the world to recruit the number of participants we will need to determine what is going on.

"We expect to need data from at least 1,000 such individuals in order to define the genetic factors associated with this extraordinary outcome," she adds. "This effort will only be possible with the collaboration of HIV researchers, providers, advocacy groups and most important the HIV-infected individuals that fall in this category."

Those eligible to participate in the Elite Controller Collaborative Study are HIV-positive adults, aged 18 to 75, who have maintained viral loads below 2,000 copies without taking HIV antiviral medications. Participation involves having a single blood sample taken, which can be done by participants' local healthcare providers. Those located near a participating research center may choose to be followed over time and provide additional blood samples.

"So far we have enrolled nearly 200 participants from 25 U.S. states, and we are looking forward to adding participants from other countries," says Pereyra. Potential participants or collaborating providers seeking more information should contact Rachel Rosenberg, Partners AIDS Research Center, (617) 726-5536 or rrosenberg2@partners.org.

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In addition to Walker, other organizers of the Elite Controller Collaborative Study are Eric Lander, PhD, director of the Broad Institute of Harvard University and Massachusetts Institute of Technology; Dennis Burton, PhD, of the Scripps Institute; Steven Deeks, MD, University of California at San Francisco; and Mary Carrington, PhD, of the U.S. National Cancer Institute. The current list of consortium members is on the next page. The project is supported by a philanthropic gift from the Mark and Lisa Schwartz Foundation.

The Partners AIDS Research Center, the project's coordinating 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.

Elite Controller Collaborative Study

Participating institutions, as of August 14 2006 Investigators

Partners AIDS Research Center/Massachusetts General Hospital     Bruce Walker, MD
Boston, Mass. (coordinating center) Florencia Pereyra, MD
Aaron Diamond AIDS Research Center, New York, N.Y. Martin Markowitz, MD
Centre Hospitalier de l'Université de Montreal, Quebec Cécile Tremblay, MD
Duke University, Durham, N.C. Barton Haynes, MD
Fred Hutchinson Cancer Research Center, Seattle, Wash. M. Juliana McElrath, MD, PhD
Imperial College, London, U.K. Jonathan Weber, MD
McGill University Health Center, Montreal Nicole Bernard, PhD
Northwestern University, Chicago, Ill. Robert Murphy, MD
Sanquin Blood Supply Foundation, Amsterdam, Netherlands Hanneke Schuitemaker, PhD
University of California at Los Angeles Otto Yang, MD
University of California at San Diego Douglas Richman, MD
University of California at San Francisco Steven Deeks, MD
University of New South Wales Australia John Kaldor, PhD Tony Kelleher, MD, PhD
Venderbilt University, Nashville, Tenn. Spyros Kalams, MD
Weill Medical College of Cornell University, New York, N.Y. John P. Moore, PhD

Other collaborating organizations:

AIDS Action Committee, Boston
AIDSmeds.com
AIDS Vaccine Advocacy Coalition (AVAC)
TheBody.com
Center for AIDS Information and Advocacy, Houston
Gay Men's Health Crisis, New York
International AIDS Society – USA
International AIDS Vaccine Inititative
Los Angeles Gay and Lesbian Center
Physicians' Research Network (PRN), New York
POZ magazine
Test Positive Aware Network, Chicago
Treatment Action Group, New York
Also more than 100 health care providers worldwide


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