An international, multi-institutional research consortium that includes the UCLA AIDS Institute seeks to discover how a few HIV-infected individuals are naturally able to suppress replication of the virus. The Elite Controller Collaborative Study, 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," said Dr. Bruce Walker, director of Partners AIDS Research Center (PARC) at Massachusetts General Hospital and an initial organizer of the Elite study. Walker discussed the project in a media briefing today at the 16th International AIDS Conference in Toronto.

For more information about the Elite Controller Collaborative Study, visit http://www.mgh.harvard.edu/aids/hiv_elite_controllers.asp.

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 non-progressors" 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 current available tests.

"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," said Dr. Florencia Pereyra 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."

"Thus far, only small groups of these rare individuals have been studied for limited questions," said Dr. Otto Yang, associate professor of infectious diseases at the David Geffen School of Medicine at UCLA, and one of the investigators. "The goal of this collaborative will be to collect large enough numbers of participants to study and compare multiple factors at once. There is probably no single factor that determines good immune control of HIV, and this is the best way to understand how various factors play different roles."

Those eligible to participate in the Elite Controller Collaborative Study are HIV-positive adults, age 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 health care 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," Pereyra said. Potential participants or collaborating providers seeking more information should contact Rachel Rosenberg of Partners AIDS Research Center at (617) 726-5536 or rrosenberg2@partners.org.

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

As of Aug. 9, participating investigators and institutions were: Dr. Bruce Walker and Dr. Florencia Pereyra of Partners AIDS Research Center/Massachusetts General Hospital (coordinating center); Dr. Martin Markowitz of the Aaron Diamond AIDS Research Center; Dr. Cécile Tremblay of Centre Hospitalier de l'Université de Montreal, Quebec; Dr. Jonathan Weber of Imperial College London; Nicole Bernard, Ph.D., of McGill University Health Center; Dr. Robert Murphy of Northwestern University; Hanneke Schuitemaker, Ph.D., of Sanquin Blood Supply Foundation, Amsterdam, Netherlands; Dr. Otto Yang of the UCLA AIDS Institute; Dr. Douglas Richman of the University of California, San Diego; Dr. Steven Deeks and Dr. Jeff
Martin of the University of California, San Francisco; and John P. Moore, Ph.D., of Weill Medical College of Cornell University, New York.

Collaborating organizations are AIDS Action Committee, Boston; AIDSmeds.com; AIDS Vaccine Advocacy Coalition; TheBody.com; Center for AIDS Information and Advocacy, Houston; Gay Men's Health Crisis, New York; International AIDS Society - USA; Physicians' Research Network, New York; POZ magazine; Test Positive Aware Network, Chicago; and Treatment Action Group, New York.

-UCLA-
ER345