A lab, a plant, a compound ten times more powerful than prostratin?

The Man: José Alcami

The Plant: Euphorbia (one of many types of Euphorbia)

Interview with José Alcami, from the the Instituto de Salud Carlos III in Madrid

Interview conducted on July 17, 2010 at the "Toward a Cure" HIV Reservoirs Workshop, Vienna, Austria

AIDS Policy Project: Thanks so much for sitting down with us. Tell us about your work.

I work in Spain in a basic research lab*. We study the mechanism of HIV latency and re-activation--we want to understand why and how the virus can remain silent in some lymphocytes [a type of immune system cell] and what are the triggers for the replication of the virus. The virus can be completely asleep in some cells.
We are interested in mechanisms of entry of the virus into cells-- how chemokines--small protein molecules that guide cells--block the entry of the virus.

[Remember: The goal is to flush out and kill the latent HIV virus in "viral reservoirs" that remain in the body even when viral load is considered undetectable.]

One thing we do is test new compounds. We receive compounds from pharmaceutical companies, universities, and small biotech companies, and we check the antiviral activity of these compounds--those that can induce activation of the virus, and some that block the entry of HIV into the cell.

To do this, we check the compounds in recombinant viruses and some cell models [HIV grown in labs rather than from people’s bodies]--they are cheap and sensitive and we can check the induction and replication.

We are studying the mechanisms by which the virus activates.

Right now we are looking a compound, jatrophane diterpene (SJ23B), that triggers SJ23 ( a cell membrane protein). It's a plant extract from a plant called Euphorbia that is found in the Mediterranean. This chemical compound is very useful to reactivate the virus. [The abstract states that SJ23B is 10 times better at activating latent virus than prostratin, another HIV activating compound.]

It's exciting--the compound works using two different mechanisms. When cells are latent, it reactivates the virus. Also, it protects  uninfected cells around any infected cells.
So it activates HIV but decreases HIV infection in culture [in the Petri dish or test tube]. The idea would be to use pulsing treatments—on again, off again.

Next step: To test the compound in mice.
Obstacles: There is not much money for basic science research in Europe.

*  Basic research is essentially test-tube and petri dish research. The work, if it is successful, is eventually tested in people. That is called clinical research.

PD-1 Inhibitors, a Curish Therapy Ready for Clinical Trials

PD-1 (Programmed Death-1--very Star Wars) is a T-cell receptor. Technically, it is a signaling receptor that appears not only on T-cells, but on other immune system cells: B cells, natural killer T cells and macrophages.

For this discussion, though, let's focus just on T-cells. PD-1 signals to T-cells not to activate. T-cell activation is when a t-cell recognizes that cells coming at it are from a particular disease and the T-cells then present a custom package of disease-fighting strategies just for that disease. PD-1 signals to T-cells not to do this.

PD-1 seems to be a way to target latent, HIV-infected T-cells so that they can be killed. Dr. Sandrina Da Fonseca from the  Vaccine and Gene Therapy Institute, in Florida, presented test tube data at the International AIDS Society HIV Reservoirs Conference (remember, when you hear the term "HIV reservoirs," it usually means AIDS cure research). The data showed that T cells taken from people with AIDS that had a lot of PD-1 also had a lot of HIV-1 DNA in them and that contributed to bigger viral reservoirs. 

So: Lots of PD-1 in cells = lots of AIDS genetic material = a bigger viral reservoir.

Photos from the Vienna AIDS Conference-Click for the Whole Image

The media center at the International AIDS Conference in Vienna, 2010

One of many huge statues on the library

Asia Russell, Health GAP member and West Philadelphia neighbor, making it happen at a press conference as broadcast on closed-circuit TV in the media room.

March ended inside the courtyard of Vienna's old library

A scientist explains what's going on in AIDS cure research.

Dr. Sharon Lewin is an MD PhD and a former post-doctoral student in David Ho's laboratory (if you don't know David Ho, google him). She was chosen to deliver a plenary speech on the cure the night the Vienna International AIDS Conference opened. It is remarkable that this ignored and marginalized subject, the cure for AIDS, actually managed to get a place on the plenary. There are barely any sessions about it during the conference itself. Sharon is from Australia, where she runs a research lab. There is not much money for AIDS cure research in Australia.  The US is spending only 3% of its AIDS research budget on a cure for AIDS, but even that money is largely unavailable to foreign researchers. This needs to change.

Sharon explains the current state of AIDS eradication research in the video attached to this blog post. It's about 1 hour, 55 minutes into the video. She speaks for about 25 minutes. It gets pretty sciencey, but stick with it because you'll learn information about cure research.

Here's the link to the video: http://globalhealth.kff.org/AIDS2010/July-18/Opening-Session-LIVE-WEBCAST.aspx

Dr. Fauci: Stop operating like a bureaucrat and start acting like a genius

Larry Kramer to Tony Fauci, asking him to lead on AIDS cure research, this morning: "Stop operating like a bureaucrat and start acting like a genius." Fauci's emailed response is below.

Controlling and Ultimately Ending the HIV/AIDS Pandemic
A Feasible Goal

Gregory K. Folkers, MS, MPH; Anthony S. Fauci, MD
JAMA. 2010;304(3):350-351. doi:10.1001/jama.2010.957

Le Deluge

I just attended a small, two-day workshop focused on the science of AIDS eradication and persistence research. "Eradication" is the study of how to get rid of AIDS; "HIV persistence" is the study of why it persists in the body even if AIDS drugs get rid of most of it. The workshop included some very complex basic science. Basic science means studying what is happening at the test tube, blood/cellular level. Clinical science is then taking that information and testing new therapies in people.

Some of the new information is embargoed, meaning I cannot write about it until it is officially released in a few days. But it is coming.

Sharon Lewin, an MD PhD from Australia, gave a preview of her plenary lecture tonight at the opening of the (bigger, six day, 25,000 people) Vienna AIDS Conference. She will be echoing the call in our report, AIDS Cure Research for Everyone for TEN TIMES more spending on AIDS cure research. Also, she showed a slide that read, in big letters, "THE CURE FOR AIDS IS A HUMAN RIGHTS ISSUE." That is the second time I have ever read that; the first was in our report. And for millions and millions of people, many with no access to treatment, the cure is their best hope.

There is a lot of important research coming from French researchers.
I wonder if the cure for AIDS will come from France, just as the discovery of the AIDS virus came from the Institut Pasteur in Paris?

I am told that it is the hottest July ever on record in Vienna, and last night the heat broke with an electrical storm. I went out in the pouring rain to find something to eat, and there, smiling and walking along with a friend under an umbrella in the rain, was Francoise Barre-Sinoussi, the Nobel laureate for discovering the AIDS virus. Perhaps it is a good sign.

Do all AIDS researchers want a cure?

Here at the HIV reservoirs workshop in Vienna, I just spoke to a Dutch researcher. I asked him when he thought there would be a functional cure for AIDS and he said never. He said he is explicitly not interested in finding a cure for AIDS; he is interested in host-virus interactions only. When I seemed surprised, he said--"If I were interested in a particular result, I would prejudice the experiment." He said, "If I were trying to cure some disease, which one would I pick? I'd be lost in the choices. Besides, the best thing to do if you are interested in ending the epidemic is to work in prevention!

I asked if he had ever met a person with AIDS, and he mentioned the patients in his community advisory board. He didn't sound very impressed.