amfAR Funds $1.4M in Grants Toward HIV Eradication
As part of its mission to accelerate promising research focused on finding a cure for HIV/AIDS on July 17, amfAR, The Foundation for AIDS Research, announced a new round of grants through its amfAR Research Consortium on HIV Eradication (ARCHE) program. Totaling more than $1.4 million, the ARCHE grants will support four teams of scientists working at leading research institutions around the world.
"Through ARCHE, amfAR leverages the expertise and innovation of distinguished scientists from across the globe to advance cure-focused research," said amfAR CEO Kevin Robert Frost. "Some of the most important recent advances in HIV research are the result of strategic collaborations among amfAR-funded scientists and are a testament to the success of our cooperative approach to research."
Earlier this year, ARCHE grantees Dr. Deborah Persaud of Johns Hopkins University and Dr. Katherine Luzuriaga of the University of Massachusetts described the case of the first child to be cured of HIV. The Mississippi child was diagnosed with HIV at birth an immediately put on antiretrovirals. She was lost to follow-up, but when brought back into care at 23 months, was found to have an undetectable viral load, despite being off treatment for five months. An amfAR grant enabled the researchers to perform highly sophisticated tests that confirmed the cure.
"The child’s pediatrician in Mississippi was aware of the work we were doing, and quickly notified our team as soon as this young patient’s case came to her attention," said Dr. Rowena Johnston, amfAR vice president and director of research. "Because the collaboratory was already in place, the researchers were able to mobilize immediately and perform the tests necessary to determine if this was in fact a case of a child being cured."
In July, another ARCHE grantee, Dr. Timothy Henrich of Harvard Medical School and Brigham and Women’s Hospital in Boston, reported on the case of two HIV-positive patients who show no trace of the virus following stem-cell transplants. The patients had been on long-term antiretroviral therapy for HIV when they developed lymphoma. To treat the cancer, the patients underwent reduced intensity chemotherapy followed by stem-cell transplants.
"These findings clearly provide important new information that might well alter the current thinking about HIV and gene therapy," said Frost. "While stem-cell transplantation is not a viable option for people with HIV on a broad scale because of its costs and complexity, these new cases could lead us to new approaches to treating, and ultimately even eradicating, HIV."
Henrich presented preliminary findings on these patients at the International AIDS Conference last July. With support from amfAR, he conducted a clinical study in which his research team withdrew the patients’ antiretroviral therapy and performed several sophisticated assays looking for signs of viral rebound in blood and other tissues. One patient has been off treatment with no detectable virus for approximately 15 weeks, and the second patient for seven weeks, with similar results. It is too soon to draw any definitive long-term conclusions, but for his promising work, Henrich was awarded an ARCHE grant.
"Dr. Henrich is charting new territory in HIV eradication research," said amfAR Vice President and Director of Research Dr. Rowena Johnston. "Whatever the outcome, we will have learned more about what it will take to cure HIV. We believe amfAR’s continued investments in HIV cure-based research are beginning to show real results and will ultimately lead us to a cure in our lifetime."
This year’s grants will enable researchers from the United States, United Kingdom, France, Thailand and Australia to collaborate on studies exploring potential strategies for eliminating HIV infection. One study, led by Dr. Eric Arts of Case Western Reserve University in Cleveland, Ohio, aims to develop and test a vaccine-like HIV treatment specific to each patient’s virus. Unlike other approaches toward an HIV cure that focus on inducing cell changes in all cells that are vulnerable to HIV infection, this treatment specifically targets the infected cells lying dormant in the viral reservoir. Dr. Arts and Dr. Yong Gao from Case Western will work with Drs. Robin Shattock, Sarah Fidler and Caroline Foster of Imperial College London to study the treatment’s effectiveness.
In another study, a team led by Dr. Nicolas Chomont of the Vaccine and Gene Therapy Institute in Port St. Lucie, Florida, has received $590,285 in grants to study HIV persistence in T-cell subsets during antiretroviral therapy. Specifically, they will investigate the subsets of CD4+ T memory cells -- the cells where the HIV reservoir mainly resides -- and the roles they may play as a potential target for a cure. Chomont will work in collaboration with three-time ARCHE grantees Dr. Sarah Palmer of the University of Sydney in Australia and Dr. Steven Deeks of the University of California, San Francisco; Dr. Jintanat Ananworanich from SEARCH in Bangkok, Thailand; and Dr. Asier Saez-Cirion of Institut Pasteur in Paris, France.
Researchers from University of California, Los Angeles (UCLA) and University of Washington led by Dr. Scott Kitchen of UCLA will use their $300,000 ARCHE grant to explore gene therapy using stem cells as a potential cure. Joined by Drs. Jerome Zack and Irvin Chen from UCLA and Dr. Hans-Peter Kiem of University of Washington, the researchers plan to modify stem cells so that they bind directly to HIV. These modified cells would then mature into a specific type of immune cells that can kill infected cells. The researchers theorize that the treatment will help to reduce the size of, and perhaps even eradicate, the viral reservoir.
The fourth study will be conducted by four-time ARCHE grantee Dr. Robert Siliciano of Johns Hopkins University in Baltimore. Siliciano will use his $180,000 grant to build on his recent finding that as many as 40- to 50-fold more cells may harbor viruses but are not counted in size estimate of the viral reservoir. Siliciano will focus on identifying those cells and their properties, and determining how the viruses may be induced out of these infected cells so they can be targeted by antiretroviral therapy.
"The ARCHE program has enabled us to gain invaluable insights into how we can potentially eradicate HIV," said Johnston. "As we enter our fourth year of ARCHE funding, we are excited at the prospect of generating further discoveries that could ultimately bring us the cure that we so urgently need."
For more information about clinical research, visit www.amfar.org.