An AIDS Patient Quits his Drugs

Dr. Tae-Wook Chun, from NIAID, in Vienna, 2010

One Patient's Story Illuminates a Whole Situation: 
Information and Commentary

Tae-Wook Chun,  a researcher at the National Institutes of Health's National Institute of Allergy and Infectious Diseases, gave a fascinating talk at the Vienna HIV reservoirs workshop. He had a patient who had been HIV+ for almost ten years, was being treated using HAART (Highly Active Anti-Retroviral Therapy) and had the lowest viral load ever recorded in Dr. Chun's lab. The patient had rarely ever even had a viral blip (a shortlived increase in viral load). Chun was using special tests to monitor the patient's viral load that are much more sensitive than the viral load tests many people with AIDS receive in their doctors' offices. Even with these sensitive tests, this patient's viral load was tiny, tiny.  The patient had been treated aggressively and early in his HIV infection ten years before.

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.

HIV Reservoirs Conference in Vienna. First, the room.

First: The room. The first HIV reservoirs workshop at the IAC is held at the University of Vienna, which appears to be a former palace. There are large statues of Austrian emperors. There are huge paintings of a man I am pretty sure is Louis XIV. The researchers are declaiming from what may or  may not be a throne. When I pan to the ceiling, what you can't quite see are colossal paintings by Klimt. Also, it is 90 degrees, and as the afternoon wore on, the comments and questions to speakers became more and more sharp and annoyed, I think because of the heat. If not for the temperature, I could stay in this room forever. Click on each image to see the full photo.  I'm not sure why the square below is black, but click on it--it works. Next up: The science.

Your Input: What would you like to ask top AIDS cure researchers?

Hi,

We're here at the two-day Reservoirs Workshop (HIV reservoirs is researcher talk for CURE research).

I'm here with the top AIDS cure researchers in the world. We have some good questions for them:

How much money are you spending to duplicate the Berlin Patient experiment?

How long will it be before we can try Paula Cannon's mice experiment in people?

What would you like to ask top AIDS *cure* researchers?

STARTING THURSDAY from Vienna: We're Blogging on a Cure!

Hi,

Starting on THURSDAY (so, soon) we will attend a special meeting on AIDS *cure* research as well as the Vienna International AIDS Conference. We will be blogging a lot, in plain English, about what we learn about AIDS cure research.

PLEASE FOLLOW US AS WE BLOG ON PROSPECTS FOR A CURE FOR AIDS:

The Cure Blog:              http://aidspolicyproject.blogspot.com/
Twitter:                           http://www.twitter.com/aidspolicyproj
Facebook:                       http://tiny.cc/vt38Y
Our web site:                  http://www.AIDSPolicyProject.org

With photos, so look out!

Study says increasing HIV drug treatment will save millions through prevention

Winnipeg Free Press: "The study was published in the U.S.-based journal 'AIDS,' the official journal of the International AIDS Society.
Montaner said the findings are the first to link savings to prevention through increased treatment.
'Until now people failed to incorporate into that cost effectiveness the fact that by treating me I am not infecting you, her, him or whoever and they are not infecting Peter, Paul, Mary and John,' he said.
'The failure of those new generations of infections to be materialized represents a huge saving,' said Montaner, who leads the BC Centre for Excellence in HIV/AIDS."

Who's the Berlin Patient?

The Berlin Patient. You may have heard about him, or his story may be news to you. If he is reading this, a warm hi from us at the AIDS Policy Project--we hope to have a beer some day with you.

So--basically, the Berlin Patient is an American man of about 40 who lived in Berlin, had AIDS and also leukemia. His leukemia doctor needed to give him a bone marrow transplant to treat the leukemia. But he used a special person as a donor--someone who was born with the "CCR5 deletion" (remember those initials) which means that the person cannot be infected with AIDS. About 1/1,000 Northern Europeans is born with this--it's a mutation.

And the rest, literally, is history.

Like the Berlin Patient, except in a mouse, and easier to do.

This is based on information from Jules Levin (www.NATAP.org), who tracks all things AIDS and research.

Basically a California researcher named Paula Cannon has demonstrated that in a mouse, if you treat human stem cells (yes, they're using a mouse that's been engineered to have a human immune system) with a new zinc finger technology, you can disrupt CCR5, which is something that HIV needs to infect cells. The healthy stem cells then reproduce and spread into many kinds of uninfected immune cells. And you don't need to do this to a ton of cells, because these new HIV-free cells you are creating spread quickly. Similar to the Berlin Patient, (he got a special stem cell transplant from someone whose immune system naturally lacked CCR5) but at least in this mouse experiment, a complete stem cell transplantation isn't necessary. Also, if it works in humans, it's a "one shot thing." OK now, we are cooking with gas. Article was in press (and possibly out of reach of most other researchers) for 9 months. Bolding is mine.

Great article on AIDS cure research by Jon Cohen

Basically a survey of the top research happening in California right now, much of it funded by the deep-pocketed, publicly funded but little-known California Center for Regenerative Medicine, California's stem cell research agency. Article discusses the Berlin Patient and the research that has followed that case (possibly the first cure of a person with AIDS).