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HIV cure is the next frontier

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Prevention was the biggest AIDS theme of 2011, with new study findings showing that early antiretroviral treatment can reduce the risk of HIV transmission by nearly 100 percent, and data demonstrating that pre-exposure prophylaxis, or PrEP, can significantly reduce infection – at least for some people, some of the time.

But many researchers and advocates are looking beyond the latest advances in antiretroviral therapy and biomedical prevention toward a goal that not long ago was considered too far-fetched to warrant serious discussion: a cure for HIV.

"Cure is the next frontier," said Rowena Johnston, vice president for research at amfAR, the Foundation for AIDS Research. "We want to make 'cure' into a family-friendly four-letter word."

AmfAR has put its money where its mouth is, recently announcing $2.1 million in grant awards with an emphasis on cure-focused research; among the 13 grants, three went to researchers in San Francisco. The funding will also cover fellowships to support promising young researchers in the HIV/AIDS field.

The resurgence in cure-related research in recent years has come from the realization that, even with today's highly effective antiretroviral drugs, people will not be able to treat their way out of the epidemic.

"Antiretrovirals are pretty good, but people have to adhere to them for a lifetime, they are costly, and they have side effects," Johnston told the Bay Area Reporter .

Further impetus was provided by the "Berlin patient," San Francisco resident Timothy Brown, who appears to have been cured of HIV after receiving two bone marrow transplants to treat leukemia, using stem cells from a donor with naturally resistant CD4 T-cells.

While the grueling and expensive transplant procedure is not suited for widespread use, it offers clues about how cells might be protected from the virus – clues that have spurred efforts to recreate this effect using gene therapy to artificially remove an HIV receptor known as CCR5 from patients' T-cells.

The International AIDS Society has made curing HIV one of its key focal areas. An IAS working group, spearheaded by Nobel laureate Francoise Barre-Sinoussi and Steven Deeks of UCSF, is developing a global scientific strategy for cure-focused research to be presented at the 2012 International AIDS Conference next summer in Washington, DC.

Local grants

Researchers are exploring a wide range of approaches to either completely eradicate HIV from the body or – more likely – cripple the virus enough that a person's immune system can keep it under control without lifelong daily treatment.

In addition to gene therapy to protect cells from infection, several strategies involve flushing latent HIV out of resting T-cells, making it vulnerable to antiretroviral drugs and immune defenses. Other strategies attempt to boost immune responses to tackle the virus.

AmfAR's local grants will fund three research teams at UCSF that are taking three completely divergent approaches to the problem. The grants are each for $120,000.

Koh Fujinaga and colleagues will study reactivation of HIV gene expression using compounds known as HDACs and PKC agonists. A better understanding of how HIV maintains latency in resting cells may aid development of therapies to eliminate this viral reservoir, enabling people to stop antiretroviral therapy without the virus coming back.

Hiroyu Hatano and her team will study whether angiotensin-converting enzyme or ACE inhibitors – a type of drug usually used to treat high blood pressure – can reduce the buildup of scar tissue in lymph nodes.

"Lymph nodes become scarred with collagen in response to HIV, and this scarring prevents immune cells that fight HIV from recognizing infected cells," Hatano explained. "We will test whether ACE inhibitors will decrease the amount of scarring and whether this helps the immune system to fight HIV better."

Finally, Douglas Nixon's team will study endogenous retroviruses, or pieces of ancient "junk" viral DNA in human chromosomes that can be reactivated when HIV infects cells; he hopes to learn more about the resulting immune response and harness it to produce a therapeutic HIV vaccine.

"In medical practice, viruses are not routinely cured," Johnston told the B.A.R. "We want to revolutionize not only how we deal with HIV, but also how we view and may ultimately eradicate a whole host of infectious diseases."

According to amfAR CEO Kevin Frost, the organization now spends 60 percent of its research grant dollars on cure-related research.

Support from independent organizations is increasingly important as government research budgets are reduced in the wake of the global financial crisis. Last year the AIDS Policy Project, a cure advocacy group, calculated that the U.S. government spends only about 3 percent of its total HIV research funding on cure-related studies.

"We're increasingly excited about the work that emerges from the cure-focused studies we fund," Frost said. "As we keep uncovering new information about the virus, we're increasingly confident that we will be able to find a cure for HIV/AIDS in our lifetime."

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