amfAR Funds Innovative Approaches to HIV Research

The Foundation for AIDS Research's sixth round of fellowships for young HIV/AIDS researchers is looking to address the epidemic in varied ways. Among topics being addressed are the infamous Berlin patient, as well as possible new vaccine trials.

"The research being done by these new Krim Fellows is exciting, innovative, and potentially groundbreaking," said amfAR Vice President and Director of Research Dr. Rowena Johnston. The grants encompass research toward a possible cure, the epidemiology of AIDS, development of a vaccine and treatment.

This sixth round of Mathilde Krim Fellowships in Basic Biomedical Research will grant $125,000 to Christine Durand, M.D., of Johns Hopkins University School of Medicine; Lucie Etienne, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle; Alon Herschhorn, Ph.D., of the Dana-Farber Cancer Institute; and Leopold Kong, Ph.D., of the Scripps Research Institute in La Jolla, CA.

Among those exciting projects include Dr. Leopold Kong's vaccine research project, which, if successful, could lead to a new vaccine trial. Kong is attempting to develop a vaccine on the basis of the protective coating of sugar-like molecules that surround the virus.

This coating is traditionally thought to hamper the development of antibodies that might form the basis of a vaccine. Kong will determine whether this protective coat can instead be turned against the virus to render it vulnerable to destruction by the body's immune system. His research will determine whether antibodies generated against these sugars might form the basis of a vaccine that could prevent infection.

As the first scientist at amfAR, Dr. Jeffrey Laurence said he "always believed we would have a cure before a vaccine. All the easy stuff has been done and it hasn't worked, so now it's a lot of trying to fund novel approaches," he added.

Dr. Christine Durand will address the case of the so-called "Berlin patient," Timothy Ray Brown, the first person known to have been cured of HIV, to determine which of the several interventions was responsible. Brown had HIV and leukemia when a bone marrow transplant from a donor lacking a key HIV receptor caused his HIV to drop to undetectable levels. After nearly four years, Brown remains HIV-negative.

Durand plans to investigate each of the three major possibilities separately: chemotherapy targeted against cancer; immune suppressive drugs; and the process of stem cell transplantation. The new information will not only help inform us about the contributions of each of these interventions to a possible cure, but may also reveal which are the most important barriers to overcome in the search for a widely available cure for HIV.

When the news of the Berlin patient first became known, amfAR formed a special Think Tank to discuss possibilities around the case. After that, two similar cases at Harvard became public, in which the patients didn't use a delta 32 donor and continued taking an antiretroviral regimen.

Researchers then began looking at whether using different conditioning or drugs would be equally effective. Additional time is needed to determine if the Harvard patients remain undetectable.

"If the Harvard cases prove true, that would indicate that they wouldn't have to go through the transplant itself and a donor; perhaps chemotherapy drugs used for the preparation of the patient would be enough," Laurence said.

These drugs are incredibly potent with a lot of side effects and even a small risk of death from the procedure itself or the conditioning, he warned, Few people are willing take that risk, given that the life expectancy for someone with HIV has reached near parity with someone who is negative.

"So then the third issue is, what can we make from those that would be a one-shot affair"" Laurence asked. That's where amfAR research comes in.

Could a person's own cell somehow create delta 32 cells? This is just one of the ways amfAR is trying to help researchers think about how to cure AIDS.

In December, the Centers for Disease Control and Prevention released their latest estimates of new HIV infections in the U.S. The statistics indicate that HIV remains a serious health problem, with an estimated 47,500 people becoming newly infected with the virus in the U.S. in 2010. A vaccine would be the best way to fight new infections.

Other Krim fellows will work on issues including cross-species transmission and finding drugs that prevent HIV from entering the cells. Etienne will work with Dr. Michael Emerman of the Fred Hutchinson Cancer Research Center in Seattle to investigate the genetic changes in the monkey version of HIV that allowed it to move to chimpanzees, then humans. They hope to better understand the risk that other viruses could make a similar leap.

In Boston, Dr. Alon Herschhorn will work with Dr. Joseph Sodroski at the Dana-Farber Cancer Institute to screen large libraries of compounds to identify leads that can prevent HIV entry at any stage of the process. The compounds may reveal new drugs that more effectively prevent the entry of HIV into target cells.

"AmfAR saw a gap about ten years ago, when the government was only putting money into large established labs. We saw a need to invest in smaller labs and replacing researchers as they aged," Laurence said. "When we saw a decrease in NIH funding again in 2005, we decided it was time to get back into the game, and to honor Dr. Krim with this special level of fellowship. Krim Fellows have to be at a higher level in terms of training, and they have an opportunity to apply for a third level of funding, to support them moving into an academic faculty position, rather than continuing with just another fellowship." Dr. Mathilde Krim co-founded amfAR with actress Elizabeth Taylor, among others.

In the past five years, amfAR has awarded more than $3 million through the program. Since it was founded in 1985, amfAR has invested more than $340 million in research and has awarded grants to more than 2,000 research teams worldwide.