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What constitutes a cure for HIV? A cure would mean that patients infected with HIV would not need to take medications to control the virus. A cure could be a “sterilizing” cure, meaning that the virus is completely eliminated from an HIV patient’s 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.
What are the approaches under development for curing HIV? 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 patient’s own immune system. One tactic for gene therapy under development targets the CCR5 gene. The CCR5 gene creates a receptor on a cell’s 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 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.
What is UCSF’s role in research towards an HIV cure? 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 grants, 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.
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