The Hunt for a Cure

The ARA has been at the forefront of HIV treatment and prevention research for 22 years, but the work of the Los Angeles-based nonprofit is now primarily focused on finding a cure. ARA president and CEO Carolyn Carlburg and Stephen Brown, ARA vice president and medical director, talked to HIV Plus about their work for a cure and why you'll be hearing the words 'prostratin' and 'reservoirs' much more in the coming years. HIV Plus: We just passed the 30th year of the first diagnosed case of AIDS. We hear a lot about prevention and treatment. Why aren't we hearing more about a cure? Stephen Brown: Part of the reason is that for many years a cure seemed too difficult a goal to pursue, and there didn't seem any widespread support for research in that area. For example, when grants came out about 10 years ago and they identified the areas of science where research really needed to be done, there was a spot on the list for persistent infections including HIV, but it really wasn't followed up with funding. The funding in this area has always been difficult to obtain and some of these [research] institutions have been under the financial pressures'the amount of institutions getting their grants funded range from 25% to as low as 8%. And so when you have situations like that, what gets funded tends to be safe research that will produce the expected results or insights'there's not a big sense of risk taking at those institutions. So it was only really two years ago that National Institute for Health began to entertain the possibility of a research program in this area. So much government funding is put toward treatment. Do politicians understand the savings that could be achieved should a cure be found? Carolyn Carlburg: The funding for research, whether for treatment, vaccine, or cure, almost 100% of it is going to come from [the National Insitite of Health]; there's not a whole lot of it right now that's going to come from big pharmaceutical companies. But NIH, I think their focus is more on the science'other departments like health and human services or maybe even the White House would be greatly influenced by achieving that kind of savings. I think NIH is focused primarily on science. I don't mean to sound critical of government, but I think different departments of agencies think about their own areas of responsibility. Much of your work involves targeting HIV reservoirs through something called prostratin. What is exactly prostratin and what exactly are reservoirs? Brown: When we're talking about the reservoirs we're talking about cells holding just the information to make HIV. For most of these cells, there are no HIV particles or pieces, all of that is integrated into the person's DNA and exists purely as the information for making HIV. These cells are programmed to kind of remain silent, but we activate it and once it's reactivated, instructions are followed and the cell begins making HIV again. Prostratin is related to several other chemicals that have been used frequently in scientific experiments in order to activate T-cells and it's this activation process that actually causes the information to be changed into virus. The important part about prostratin is while it does cause activation, it doesn't cause these cells to proliferate or replicate, and that's very pretty important because if you give someone something that could replicate, that's often the beginning of something like a cancer. But prostratin is very closely related to something that's been already been tried, and given clinical trials for some other diseases. We think prostratin is safer then those chemicals. Carlburg: The way the anti-HIV drugs work is they primarily block and suppress the replication of virus. The irony is that you can't get rid of the reservoirs because the virus has become latent. So, if it's not replicating then we can't kill it. We want to find a safe way to attack it. You're trying to find a way to cure it without it advancing from HIV to AIDS. Carlburg: Exactly. So in a way we want to do the opposite of the antiretrovirals do. We want to drive it to the point where it can't replicate, but we want to make it visible where we can attack it. Brown: So the immune system sees [HIV] and the cells keeping it there in a reservoir latent stage are activated or killed by the immune system or killed by the replication of the virus' similar in what you might do in a cancer protocol if you're trying to get rid of a certain number of tumor cells. You might do something that might get rid of 15-20% with each round. Can you talk about how it was first developed? Brown: The traditional use for prostratin is in Samoa, where it's given as a tea to treat hepatitis. And as a tea, prostratin would go right from your intestines into the liver so it's a good way to get that administered. It's derived from a tree called the Mamoa tree. We actually went to Samoa and we observed two of the healers prepare the samples of the tea and we brought samples home. They cut off a piece of the tree and basically scrape off the outer part, which is the very thin bark of the tree. Then there's this stuff underneath before you really get to the wood and that's the part that they scrape off and use to make the tea. How did you first found out about it? Brown: It first came to my attention in 1999. The information was being presented by Dr. Michael Boyd from the National Cancer Institute. It was a small invitation-only scientific conference held in Ventura, Calif., that year. I was invited and went and we had been looking for chemicals or potential drugs or interventions that did precisely what prostratin did. So when I saw the information at the conference I was very excited, spoke to the presenter, he sent us some samples, and I went to Washington and saw where they had done some work at NCI. So, we were able to obtain a significant amount [of prostratin samples] which we then began using primarily by funding other researchers [to work with it]. It was hard to get anyone interested in looking at this so we had to fund them to do the initial experiments. But when [the science community] saw the results, suddenly everyone was excited. In 2009, you were granted the rights to the technology used to synthesize prostratin. What's the latest on your work with prostratin and reservoirs? Carlburg: We basically pulled together hundreds of pages of data and information on prostratin. Brown: We felt quite encouraged by the FDA's response [to the documents] but they did have a series of experiments that they wanted us to conduct. So, we are currently in the beginning stage of doing those experiments.