Researchers are studying several approaches to curing HIV. A wide range of drugs is still being researched in the hopes they could purge latent HIV from memory CD4 cells and other reservoirs. Enhancing the ability of the immune system to kill HIV is being studied, as is "epigenetic regulation" -- the genetic signals that enable HIV to remain in hiding. If these are understood, there may be a way to force HIV out into the open where medications can attack it.
While most strains of HIV use the R5 receptor to enter a CD4 cell, some use the X4 receptor. An ideal therapy would block or delete genes for both the R5 and X4 receptors, and one group is studying a gene therapy targeting the X4 receptor. Craig Wilen, a biomedical graduate student at the University of Pennsylvania, reported on efforts to design a therapy that knocks out the X4 receptor. Using the same zinc finger nuclease approach, the team disrupted the X4 receptors on human CD4 cells, and then injected them into mice which were then exposed to HIV. The gene therapy seemed to protect the mice from HIV infection. These studies are still in their earliest stages and have a long way to go before we will know if these therapies are safe and well-tolerated.
Another new approach is being pursued in a drug called KP-1461, which works by increasing HIV's rate of mutation. HIV has a very high mutation rate, allowing it to become resistant to many of the medications that fight it. But this may also be its weakness. KP-1641 has been shown to cause "viral decay acceleration" in the lab. In the presence of the drug, HIV mutations accumulate over time and eventually the virus mutates until it is no longer viable. While the test tube results are promising, clinical trials are needed to prove its efficacy in people, and are under way.
That's the $64,000 question. Most researchers have stopped trying to predict when a cure might be available, especially after learning from the many wrong predictions regarding a vaccine. Years ago, the standard line was, "We'll have a vaccine in ten years." After numerous missed deadlines, no one makes such predictions any more. But Jay Lalezari recently told the Bay Area Reporter, "Whether a cure is going to come from one approach or some combination, I do think it's possible that in our lifetime we'll be curing HIV."
The question surrounding a functional cure may not be "if" but "when?" The bigger question is how quickly will the needed research get done? In 2009, NIAID spent $40 million on AIDS cure research. But its total AIDS budget was $1.5 billion, meaning that less than 3% was spent on cure research. Worldwide, less than 1/3 of people with a CD4 count below 500 are receiving HAART. Without a functional cure, millions will be dependent on world leaders and international charities to pay for the drugs they need to stay alive. Meanwhile, even those with access to excellent treatment still suffer from diseases of premature aging or heart attacks and kidney problems as a result of a persistent virus that causes long-term inflammation.
There have been only 12 clinical trials at the NIH's Division of AIDS focused on a cure since 2005. Of those, three are enrolling, three are in development, and three are "pending." This means that there is little translation of basic science into producing cures that could be used by people. So far, there have been trials of gene therapy, intensifying HAART, therapeutic vaccines, and the efforts to purge HIV reservoirs, but much more work is needed.
Community action is needed to push Congress and the NIH to make a cure for AIDS a top funding priority. The AIDS Policy Project (aidspolicyproject.org) is calling for a funding increase to $240 million. They're also helping researchers cut through red tape, encouraging them to work together and share information, and advocating for new treatments to be tested in people as soon as it is safe to do so.
Finding a cure won't be easy, but with a real effort it could be a reality sooner than we think.
Mark Milano is an HIV health educator and the editor of Achieve. Donna Kaminski is a resident physician at Somerset Medical Center.
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