amfAR, The Foundation for AIDS Research

Entering Third Year, amfAR Consortium Gathers Momentum in Quest for HIV/AIDS Cure

Three teams of leading scientists receive amfAR funding in collaborative effort to pursue HIV eradication

For Immediate Release
Media Contact:
Cub Barrett, Program Communications Manager
(212) 806-1602

NEW YORK, June 19, 2012—Building on momentum generated by the two-year-old amfAR Research Consortium on HIV Eradication (ARCHE), amfAR, The Foundation for AIDS Research, on Tuesday announced a third year of funding that will help three research teams accelerate their groundbreaking work.

“We’re thrilled that ARCHE is working as we had hoped it would: It’s helping us, collectively, make great strides in our understanding of how to potentially eradicate HIV,” said amfAR CEO Kevin Robert Frost. “As an increasing number of prominent researchers are proclaiming that they, too, believe a cure is possible, amfAR is proud to continue to be at the forefront of cure research.”

“When we first envisioned ARCHE we hoped we would help accelerate the search for a cure for HIV/AIDS by promoting collaboration among leading scientists,” said amfAR Vice President and Director of Research Rowena Johnston. “The progress our research teams have made during just the past two years has far outpaced our expectations. It’s exciting for us to see how each new discovery opens a whole new set of doors, and how our researchers respond to the challenge.”

A series of studies to be continued by third-time ARCHE grantee Dr. Sarah Palmer of the Swedish Institute for Infectious Disease Control and Karolinska Institutet will build on an intriguing finding made during year two of ARCHE: the discovery of identical clones of latent virus. She will work with Dr. Frederick Hecht of the University of California at San Francisco (UCSF) to understand how such clones might arise and what they mean for efforts to rid the body of the virus. The team will enlist the help of Dr. Daniel Douek of the National Institutes of Health (NIH), who will apply his expertise on T cells to help explain the findings.

Third-time ARCHE grantee Dr. Robert Siliciano of Johns Hopkins University will continue to investigate the ability of disulfiram—a drug approved by the U.S. Food and Drug Administration that was recently identified in a test tube as a drug that might flush virus out of latently HIV-infected cells—to flush the virus out of infected cells. His study is based on his previous work with ARCHE researcher Dr. Steve Deeks, with whom Dr. Siliciano developed a clinical trial that produced preliminary evidence that disulfiram can reverse HIV latency. Dr. Siliciano will continue to investigate how to best use disulfiram while also searching for more potent drugs that could accomplish the same goal.

The third study, also run by Dr. Siliciano, will continue to probe the challenges inherent in using drugs to mobilize virus out of latently infected cells. Dr. Siliciano plans to determine whether all copies of the latent HIV can be fully reactivated and, if not, why some of those copies remain stubbornly in place. Understanding the characteristics of virus that remains latent will have important ramifications for the design of HIV cure strategies.

ARCHE-funded research teams and their projects are as follows:

Swedish Institute for Infectious Disease Control and Karolinska Institutet, Solna, Sweden
Sarah Palmer, Ph.D. – principal investigator
Frederick Hecht, M.D. – collaborating investigator (UCSF)
Daniel Douek, M.D., Ph.D. – collaborating investigator (NIH)
Identifying HIV-infected T cell clonotypes by single-cell sequencing: Drs. Palmer and Hecht will continue their research on identifying exactly which cells are harboring the latent HIV that is resistant to eradication by antiretroviral therapy. In their previous ARCHE research, they identified patients who harbor several identical copies of the virus, and they hypothesize that this occurs because latently infected cells make copies of themselves, and the virus they contain, and thus maintain the reservoir of latent virus. They will enlist the help of Dr. Douek to determine exactly which kinds of immune cells are producing the identical clones of the virus, and whether the same or similar cells are producing these identical viruses found in the blood versus in the tissues. Understanding the characteristics of the cells perpetuating the survival of the virus despite antiretroviral therapy will allow researchers to design specific interventions to clear the remnants of the virus and thus cure HIV.

Johns Hopkins University, Baltimore, M.D.
Robert Siliciano, M.D., Ph.D. – principal investigator
Reactivation of latent HIV-1 through a novel pathway: Dr. Siliciano hypothesizes that clearing latent HIV – the virus that cannot be targeted by antiretroviral therapy – will require agents that reverse the processes that allow the virus to lie dormant within infected cells. In his previous ARCHE research, he demonstrated that the FDA-approved drug disulfiram can reverse HIV latency (and a clinical trial conducted by him and ARCHE researcher Dr. Steven Deeks of UCSF demonstrated preliminary evidence that this may in fact be the case). In his quest to find more powerful agents, Dr. Siliciano has discovered that HIV can maintain its latency through a previously undiscovered mechanism that can be reversed by disulfiram. He will characterize this mechanism more closely, and search for more potent drugs to achieve an even greater effect, bringing us closer to a cure for HIV.

Johns Hopkins University, Baltimore, MD
Robert Siliciano, M.D., Ph.D. – principal investigator
Analysis of non-induced proviruses as a barrier to HIV eradication: One of the principal strategies being investigated to cure HIV involves using drugs that can activate HIV out of a latent state, thus allowing it to be targeted by antiretroviral therapy. Dr. Siliciano’s previous ARCHE research has identified agents that might achieve such reactivation, and he has also identified a challenge with this strategy, namely that the cells out of which the latent virus is reactivated do not always die. In a further investigation of the reactivation strategy, Dr. Siliciano plans to determine whether all of the latent virus can be reactivated. If not, he plans to characterize those viruses that are not reactivated, including descriptions of the mechanisms whereby they remain latent despite drugs that are intended to reverse that latency. Understanding the ability of the viruses that remain stubbornly latent to persist and replicate will have important ramifications for the design of HIV cure strategies.

About amfAR 

amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested more than $366 million in its programs and has awarded grants to more than 2,000 research teams worldwide.