Jay Levy, MD, co-discoverer of HIV
The advent of combination antiretroviral therapy in 1996, and patients success using the drugs in managing HIV, led to diminished interest in research towards a cure for a number of years. Here's a Q&A from UCSF:
Q: Why is there new interest in finding a cure for HIV?
A: The advent of combination antiretroviral therapy in 1996, and patients success using the drugs in managing HIV, led to diminished interest in research towards a cure for a number of years. This changed in 2009 when the New England Journal of Medicine published the case of the Berlin patient. The patient, diagnosed with HIV in 1995, was on antiretroviral medications in 2006 when he was diagnosed with leukemia. Failing treatment for leukemia, he received a stem cell transplant from a person who is naturally resistant to HIV infection. Since that extremely risky procedure in 2007, the Berlin patient has been cured not only of leukemia, but of HIVhe has not been on any anti-HIV medications since the transplant, and doctors cannot find HIV in his body using any standard tests. The patient was cured because, with the transplant, he inherited immune system cells that lack a particular receptor on their cell surface, known as CCR5. Without this receptor, HIV cannot open the door to cells and enter them. While the exact transplant procedure has a fatality rate of roughly 20 percent and thus is not likely to be replicated in more than a handful of cases in which an HIV patient has either leukemia or lymphoma and has failed cancer chemotherapy, the case has dramatically energized and expanded research efforts towards a cure using new technologies and/or advanced therapeutic products in novel combinations.
Q: Why is a cure needed?
A: Even though existing anti-HIV drugs have dramatically changed the course of HIV disease for many patients, particularly in countries of the West and other regions worldwide, the drugs are expensive and require daily dosing for life, they are not available to everyone who needs them, they have side effects and they do not fully restore health. In addition, HIV continues to kill millions of people in developing countries, including regions of Africa, Asia and Eastern Europe.
Q: What is happening with work toward an HIV cure at the XIX International AIDS Conference being held July 22-27 in Washington, D.C.?
A: An International AIDS Society (IAS) scientific working group, co-chaired by Nobel Prize winner Françoise Barré-Sinoussi, PhD, and Steven Deeks, MD, professor of medicine at the UCSF Division of HIV/AIDS at San Francisco General Hospital and Trauma Center, will release a Global Scientific Strategy Towards an HIV Cure at a 2-day symposium that will be held on July 20 and 21 in Washington D.C., immediately preceding the conference. According to the society, the strategy aims at building a global consensus defining scientific priorities for HIV cure research.
Q: What constitutes a cure for HIV?
A: A cure would mean that patients infected with HIV would not need to take medications to control the virus, similar to the case of the Berlin patient. A cure could be a sterilizing cure, meaning that the virus is completely eliminated from an HIV patients body, or a functional cure. A functional cure would stop the virus from replicating and diminish the latent reservoirs where HIV hides without completely eliminating the virus from the body. It would allow patients to control HIV without having to take medications.
Q: What are the approaches under development for curing HIV?
A: One approach would be to target the latent reservoirs, the places and types of cells in the body where the HIV virus can hide or lie dormant, which allow it to persist in patients even after years of successful suppressive therapy. Therapies would be developed and deployed that flush the virus out of its hiding places allowing either antiretroviral drugs or the immune system to kill the virus.
Another approach would use gene therapy to modify an HIV patients own immune system. One tactic for gene therapy under development targets the CCR5 gene. The CCR5 gene creates a receptor on a cells surface that acts as a doorknob for HIV to enter immune cells. About 1 in 100 Americans lack the CCR5 gene, though as many as 1 in 10 lack the gene in some northern European countries. People lacking this gene have been able to naturally resist infection despite repeated exposures to HIV. The Berlin patient received a stem cell transplant from an individual who lacked the CCR5 gene. The hope is that by shutting off the CCR5 gene, HIV can be reduced and possibly controlled by patients own immune systems without them having to take medications. A variety of projects are testing this approach, with various methods being studied to modify the CCR5 gene, some seeking to modify the disease fighting T-cells that HIV targets and kills, and some seeking to modify blood-forming stem cells.
A third approach would be to deploy products that boost the immune system. Therapeutic vaccines that boost the immune system by stimulating specific responses against HIV in infected patients are under investigation. In addition, research is under way testing approaches boosting immune responses by increasing production of certain immune system components, such as interleukin-7.
A cure could involve either a single approach or, more likely, a combination of approaches, which might include some or all of the ones listed above. The goal is to have a strategy that could eventually be delivered to people infected with HIV throughout the world.
Q: What is UCSFs role in research toward an HIV cure?
A: Steven Deeks, MD, professor of medicine at the UCSF Division of HIV/AIDS at San Francisco General Hospital and Trauma Center, is co-chair of the IAS Global Working Group that is developing the Global Scientific Strategy.
In addition, UCSF scientists are involved in two of three Martin Delaney Collaboratory grants awarded in June 2011 by the National Institutes of Health. The grants are specifically designed to advance progress toward a cure for HIV. These cure-focused teams consist of public-private partnerships between government, industry and academia and the funding for all three projects totals more than $14 million per year for up to five years.
One Delaney grant, the Delaney AIDS Research Enterprise to Find a Cure (DARE), has Deeks as one of its primary investigator and includes Joseph (Mike) McCune, MD, PhD, and Hiroyu Hatano, MD, MHS, from UCSF and Joseph Wong, MD, and Steven Yukl, MD, UCSF faculty from the San Francisco Veterans Administration Medical Center.
One of the other Delaney grant, the Collaboratory of AIDS Researchers for Eradication (CARE), includes investigators Warner Greene, MD, PhD, Eric Verdin, MD, and Melanie Ott, MD, PhD from the UCSF-affiliated Gladstone Institute for Immunology and Virology, along with B. Matija Peterlin, MD, from UCSF. Both Collaboratories are focused on understanding latency, defining and purging reservoirs and enhancing immune system function
In addition, Jay Levy, MD, co-discoverer of HIV, is also conducting NIH funded research towards a cure.
The cure research underway at UCSF and affiliated institutions is buttressed by robust, dynamic links between investigators and the HIV/AIDS advocacy community, which has taken a strong interest in cure related research.
The AIDS Research Institute (ARI) at UCSF. UCSF ARI houses hundreds of scientists and dozens of programs throughout UCSF and affiliated labs and institutions, making ARI one of the largest AIDS research entities in the world.