A report appearing in Science today entitled "The major genetic determinants of HIV-1 control affect HLA class I peptide presentation" is the culmination of the efforts of over 300 collaborators on 6 continents and is a testament to the power of collaboration, philanthropy and volunteerism in scientific research.

HIV control and genetics
While most people who become infected with HIV progress within a year to develop AIDS, it has been known for over 20 years that a small minority remain healthy without treatment, in some cases, for decades.

Dr. Florencia Pereyra

When Florencia Pereyra, MD began her postdoctoral fellowship with Bruce Walker, MD at what is now the Ragon Institute, her hope was that studying these “HIV Controllers” would unlock the secret to their genetic control and open the door to the development of a vaccine.

Early studies showed that certain genes involved with the HLA system were important for HIV control but, says Paul de Bakker, PhD, of the Broad Institute and Brigham and Women's Hospital and co-senior author of the study, “The problem was we did not know why— what about the HLA genes was so critical to outcome, and did this have anything to do with the way that these genes were known to assist in immune recognition?”

Collaboration across disciplines
In 2006 the HIV Controllers Consortium was established, and Dr. Pereyra began her attempt to recruit sufficient HIV controllers to do a genome-wide association study (GWAS), in which the variability in the human genome in controllers and progressors would be compared. DNA was extracted from each patient, and sequencing of one million areas of variation called “single nucleotide polymorphisms (SNPs) was done on each subject.

The project was expanded in 2008 with additional funding from the Bill and Melinda Gates Foundation, merging the clinical and immunologic expertise of the Ragon Institute with the genetic expertise of the Broad Institute. The results of the study narrow down the genetic determinants that influence HIV control to a few amino acids out of the 3 billion nucleotides in the human genome. This indicates that the immune system is what is making a difference in disease outcome, and that the peptide-HLA interaction is a key factor influencing how well the system works.

The Ragon and Broad institutes alike were established to foster scientific collaborations across traditional disciplines and the GWAS study is a great example of the power of such collaboration.

The role of philanthropy
Without the generous contributions of private donors, this collaboration and research would not have been possible.

In 2006, it was a gift from the Mark and Lisa Schwartz Foundation which launched the HIV Controllers Consortium when doors to funding from traditional sources were closed. With this gift, the Ragon Institute was able to recruit the patients that form the basis of the GWAS study. The data generated with their support is what ultimately led to funding by the Gates Foundation, leading to a further expansion of the study.

The contribution of patient volunteers
Nearly 1,000 HIV Controllers and 2,600 individuals with progressive HIV infection provided samples to the GWAS study.

This was by no means a small effort, involving over 300 collaborators worldwide. In some cases, it required a patient to travel to Boston in order to give a sample. These samples make up a truly impressive repository that will support immunology research well into the future.

Celebration and rededication
“There is no doubt still a long way to go,” Ragon Institute director and study co-senior author Dr. Bruce Walker said to his fellow collaborators. “But we should take a moment to celebrate the new knowledge we have created and rededicate ourselves to translating this information into interventions that will ultimately benefit patients.”

“The fact that some of the people in this cohort have been infected with HIV for 30 years and are doing entirely well shows us that the body can get the upper hand against this virus. This to me is extremely encouraging, and hopefully we can use the information from this study to ultimately harness the immune system for everyone to do an even better job at what it was designed to do."

Learn more:
	MGH Press Release: “Small protein changes may make big difference in natural HIV control – Variations in protein structure impact effectiveness of immune response” [pdf]
	Getting a Firm Grasp on HIV Control - article from the Broad Institute of MIT and Harvard
press coverage:
	In people immune to AIDS, team finds a crucial genetic clue - Boston Globe
	Protein Differences May Explain Long-Term HIV Control - MSN Health
	HIV immunity is all in the amino acids - Nature News
	Clue to how some 'control' their HIV without medication - BBC Health News
	Protein Differences May Explain Long-Term HIV Control - US News Health
	Genetic Secret to AIDS Immunity Found - Technology Review
	Genetic Analysis Shows What it Takes to Control HIV Naturally - HHMI News
	Protein Differences May Explain Long-Term HIV Control - Businessweek
	Small protein changes may make big difference in natural HIV control - Genetic Engineering and Biotechnology News
	Study offers new clues to effective HIV vaccine – Reuters
	Scientists Find Key Protein Changes Responsible For Natural HIV Control – The AIDS Beacon
	How to control HIV infection naturally – Times of India
	Researchers identify protein fragment that allows HIV patients to control disease without medication – Newark Star-Ledger
	Researchers find another piece to the AIDS puzzle – Philadelphia Inquirer
	Mystery of AIDS immunity may be solved – The Independent (U.K.)
	Genetic study shows how HIV controllers get their groove – Discover
	Key to Long -Term Survival with HIV/AIDS Discovered – Voice of America
	Immune gene variants help stop HIV – Science News
	Immune Variants Help Some People Reject HIV – MedPage Today
	The Lucky Genetic Variants That Protect Some People From HIV – National Public Radio
	Tiny variants in protein are key to natural HIV resistance – Agence France-Presse
	Study may hold key to why some with HIV don’t get AIDS - Toronto Star
	Scientists Find Key Protein Changes Responsible For Natural HIV Control - The AIDS Beacon

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