And so this is Christmas.

"What this group in Philadelphia has so miraculously done is reignite this issue and run with it." –Larry Kramer, playwright and AIDS activist icon

“To someone like me, this means more than you know. –HIV-positive young man in rural Pennsylvania                                                               

Dear Friends,

Please make a donation to the AIDS Policy Project and join our campaign to push the search for a cure for AIDS. Your money will go straight to bold, effective, and original activism.

We are shaking things up. We are working with the world’s leading researchers and reminding them that the world still desperately needs a cure for AIDS. We are calling out the National Institutes of Health for spending only 3% of its AIDS dollars to actually find a cure—a fact no one knew until we got the information after a five-month campaign.

In one year, we've put the cure back on the map in the AIDS community and we’re helping to make the cure cool again in the research community. Our campaign was on the cover of POZ Magazine. Our executive director was chosen as one of the top 100 activists in the US.  Researchers are citing our influence in their own articles. This blog even won an award; it's read from San Francisco to Soweto.

Please join us to fight for a cure for AIDS. Make a tax-deductible contribution to the AIDS Policy Project:

We are calling for more funding for the science, and new models of medical research that encourage collaboration and move faster. We are helping scientists remove bureaucratic roadblocks that prevent them from pushing forward toward a cure. With your help, together, we can do it.

We are doctors and nurses, longtime AIDS activists and college students--the only organization laser-focused on a cure.

Happy holidays. It's time for a cure!

Kate Krauss, for everyone at the AIDS Policy Project

AIDS Policy Project

5120 Walton Avenue

Philadelphia, PA 19143 

tel: 215-939-7852 

(we have members all over the US)

White Paper on New Models for Accelerated Drug Discovery and Development Is Released

Kauffman Foundation: "Five leaders in the medical innovation field released a white paper today titled The New Role of Academia in Drug Discovery and Development:  New Thinking, New Competencies, New Results.  This white paper reflects key recommendations from a July 2010 town hall meeting in Kansas City hosted by Friends of Cancer Research, Kansas Bioscience Authority, The University of Kansas Cancer Center, Ewing Marion Kauffman Foundation and Council for American Medical Innovation.

"The white paper outlines how government, nonprofit organizations and academic institutions can define new models of working with the private sector to enhance drug development efforts and bring safer, more effective drugs to the market more efficiently. ...

"'This white paper outlines critical steps toward much-needed increased interagency collaboration,' said Dr. Ellen Sigal, Chair, Friends of Cancer Research. 'The proposals discussed within this document aim to accelerate the process to help get scientific breakthroughs to patients. The message is clear; without collaboration among all agencies and academic centers, the full potential of biomedical research may be stifled.'"

More info: http://www.focr.org/kansas-town-hall.html

Speech on a cure for AIDS to the Philadelphia Town Meeting.

Local medical students listen to Dr. Kostman at our town meeting.  
Photo by Harvey Finkle.

There's lots more to say than this--I could talk about the need to actually support (and not just say one supports) new ideas, and back them up with funding. Like the idea that has, so far, cured the Berlin Patient of AIDS. Or the new idea that is curing mice in Southern California. Even if those ideas come from regular doctors, and not AIDS researchers. Or from brilliant researchers who are starved for funding simply because they live in Europe and not the US.

I could talk about the obstacle course thrown up by funders, institutional review boards, the FDA, and other bureaucracies in front of even the best researchers and the most brilliant ideas. We need the brightest scientists, not people who are smart at negotiating red tape or gaming the system because they have to. We are at a pivotal moment in the AIDS pandemic--a moment of great opportunity, if we recognize it, and act.

A cure for AIDS, whether it is developed in Bethesda or Madrid, would save 30 million lives and the US government $17 billion per year. Yet the NIH is spending only $40-$60 million on AIDS cure research. Where are the great philanthropists to support a cure? We need you. We also need President Obama, federal officials, and drug companies to step up. We saw that President Obama called for a cure for AIDS in his World AIDS Day proclamation--the first time a cure has been mentioned since at least 2005. But without the proper support, including more funding, we will lose an opportunity to save millions of lives. 

Can we be the generation that ends the AIDS pandemic?

Here's what I said to our friends in Philadelphia, many of whom are AIDS prevention activists, at our town meeting on a cure.

Winners: Who HAS doubled the budget of the NIH?

The National Institutes of Health has been flat funded since 2003, and due to high biomedical inflation, the lack of money is eating into major research opportunities for major diseases, a fact that has somehow escaped the attention of the American people.

Love him or not, former Representative Newt (short for Newton) Gingrich helped double the size of the National Institutes of Health when he was Speaker of the House of Representatives. We at the AIDS Policy Project always like to identify who actually did what. 

The clock is ticking.

On Friday, I was in downtown Philadelphia with my colleague Jose Demarco talking to the staff and clients of a local AIDS organization; we have a town meeting this Thursday.  I was explaining the case of the Berlin Patient and the follow up research taking place. People were fascinated, and a small crowd gathered around me. 

One man said, "My partner has that, (the CCR5 deletion that helped cure the Berlin Patient), and we're always trying to enroll in cure studies, but no one seems to be interested." I said that we are going to be collecting a list of people who want to participate in cure research. 

Then I pointed out that many researchers don't realize that people with AIDS still need a cure, since there are effective treatments. The group fell silent. They were stunned--They could not believe that researchers didn't know that they desperately want a cure.  Then there was a flurry of conversation and people wanted to know how they can send a message to researchers that people with AIDS need a cure.

We talked about what it's like to have HIV, even if you have access to AIDS meds. You could have an AIDS-related heart attack, or get lethal liver cancer or AIDS-related lymphoma that your body can't fight off. I have lost friends this way. A lot of people seem to be developing cognitive problems, including dementia. You can get facial wasting, or wasting through your whole body, or a hump on the back of your neck that tells the world you have AIDS. People seem to slide ominously from youth to old age.

Picture these people in the hundreds of thousands.

But the US is only a sliver of the global AIDS epidemic:  We are home to about 1/33 of the people with HIV in the world.  Of the roughly six million people who urgently need AIDS drugs right now, only 20%-30% have access to medication. The others are dying. And we may be at a high water mark for access to AIDS treatment--wealthy countries are cutting funding for AIDS treatment for people in developing countries. Getting treatment will be a struggle for them for the next 50 years, if they are successful. But without treatment now, they won't live to see a cure.

When you think about AIDS cure research, remember this: The clock is ticking. For people with AIDS in the US. And for the millions and millions of people in developing countries who are dying just like it's 1989. We need a cure.

Town Meeting on a Cure for AIDS: Philadelphia (November 18)

Please forward widely:

The AIDS Policy Project is sponsoring an AIDS CURE town meeting in Philadelphia on Thursday, November 18th, 2010. There is major research taking place that is pushing us closer to a cure. The stakes are huge for the 33 million people with AIDS, most in developing countries, most with no access to AIDS drugs. We will talk about the science and the global health implications of cutting-edge AIDS cure research.

Jay Kostman, MD, HIV physician and researcher, will examine the science, and activists will discuss a new campaign.

November 18, 7 pm, 1501 Cherry Street, Philadelphia, PA
RSVP:  info@AIDSPolicyProject.org

Snacks will be provided.

Los Angeles Town Meeting on AIDS Cure Research

TOWN MEETING ON NEW PROGRESS TOWARD A CURE FOR AIDS

November 3, 7:00 pm

Plummer Park Community Center, 7377 Santa Monica Blvd, West Hollywood, Rooms 5 & 6

The AIDS Policy Project is holding a public town meeting to discuss some exciting new AIDS cure research, as well as a new grassroots, activist campaign for a cure AIDS.

The meeting will feature a talk by two scientists, Paula Cannon, PhD, from the University of Southern California; and Dr. John A. Zaia, from City of Hope Medical Center in Duarte, CA. Both are studying ways to change the immune cells of people with HIV to make them resist HIV infection; the HIV-resistant cells would then replace infected cells. This work follows up on the 2008 case of the Berlin Patient, who was cured of AIDS through a bone marrow transplant using a donor who was born immune to HIV. The event is being co-sponsored by AIDS Project Los Angeles and CIRM, California’s state stem cell agency. The AIDS Policy Project's cure campaign is the subject of the cover story of this month's issue of POZ Magazine (www.POZ.com).

Says Kate Krauss, Executive Director of the AIDS Policy Project, “Most people don’t realize that a patient was cured of AIDS in 2008. California is leading the way in both funding and actually doing the critical research that follows up on that case and might lead to a cure for millions of people. Thirty-three million people have AIDS right now, and most can't get treatment. It’s important for the community to stand up and say, ‘we need a cure.'”

The town meeting is open to the public and anyone with an interest is encouraged to attend. While not required by organizers, RSVP emails from attendees to info@aidspolicyproject.org or call 215-939-7852. For more information about the cure campaign, see www.AIDSPolicyProject.org   Please spread the word.

Elite Controllers Display Higher Activation on Central Memory CD8 T Cells Than HIV Patients Successfully on HAART

AIDS Research and Human Retroviruses:: "Factors other than the size of the viral reservoir should explain the high level of activation of central memory CD8 T cells characteristically seen in HIV individuals with spontaneous control of viral replication."

Comment: It seems likely that this immune activation is helping these patients control HIV.

New HIV Eradication Study in Progress

AIDSmeds: "Cytheris has announced the launch and recruitment of a new Phase II study of the company’s interleukin-7 (IL-7) drug—combined with the entry inhibitor Selzentry (maraviroc) and the integrase inhibitor Isentress (raltegravir)—with the goal of eradicating HIV."

First patient treated in Geron stem cell trial

Reuters: "Geron, whose shares were up 6.4 percent on the Nasdaq late on Monday afternoon, has the first U.S. Food and Drug Administration license to use the controversial cells to treat people, in this case patients with new spinal cord injuries. It is the first publicly known use of human embryonic stem cells in people."

Our AIDS Cure Campaign Made the Cover of Poz Magazine!!

Please check out www.Poz.com or get a newsstand copy--our TEN MONTH-OLD AIDS cure campaign made the cover of Poz Magazine!! There are five articles in total about a cure for AIDS. 

Also consider going to our web site, pressing the donate button and making a contribution to keep us going: www.AIDSPolicyProject.org

Check back later; we will blog about the articles and also discuss the state of the campaign for a cure for AIDS soon. 


Thanks to Poz for covering the research and activism that are working hand-in-hand to get us to a cure.

This Tuesday: Casual dinner to discuss AIDS cure campaign (San Francisco)

The AIDS Policy Project launched its AIDS cure campaign 10 months ago, and so far, it's going amazingly well. Two of our board members, Stephen LeBlanc and John James, are in town at the same time, so we're having a super casual meeting of people who are interested in learning more about the campaign and might want to get involved.  We're just going to grab dinner and chat.

Time and place: 

THIS Tuesday evening at 6:30 pm at the Red Jade restaurant at 245 Church Street (it's at Church and Market Streets).

If you think you might want to come, RSVPs are useful but not necessary; shoot us an email at info@aidspolicyproject.org

Look forward to seeing you--

Katie Krauss for the AIDS Policy Project
www.AIDSPolicyProject.org

ps: Check out our report, AIDS CURE RESEARCH FOR EVERYONE, a plain-English primer on some of the stuff we're thinking about (that caught the attention of CNN). We also have a super-simple new fact sheet. Both are available at www.AIDSPolicyProject.org

An AIDS activist participates in a clinical trial for the cure.

It seems like a long time, about a half of my life, that I’ve lived with HIV. Looking back on the days when HIV was not even named yet I can hardly believe I have survived this long. My struggle for survival has been rocky yet I’m lucky to be alive despite the toll on my battered immune system by a devious virus. But I’ve also been tenacious and resilient in trying drug after drug and enrolling in many risky clinical trials, always looking forward to the next treatment, making it to a ripe old age of 54. 

Almost from day one I read everything there was about this disease. I ordered fact sheets from Project Inform where I am now on staff, leading advocacy efforts to find a cure. I taught myself, as many of my comrades did, to learn all there was to learn about HIV and the immune system it attacked. As a member of ACT UP I was arrested in civil disobedience actions, fighting for everything from stigma and discrimination to NIH funding and FDA inaction. Things have quieted down due to the success of the very drugs many people tested in those clinical trials. But I recognize that a life of antiretroviral medications just won’t cut it, for me and for the millions of HIV+ people, especially when there is now a concentrated effort to find a cure. I feel like we deserve an end to this fight.

Today, almost 22 years after my diagnosis I am in an early phase clinical research study to test a gene therapy concept that may lead to more answers towards a cure.

AIDS Quest to Kill `Sleeping' Virus Enlists Merck Cancer Drug

AIDS Quest to Kill `Sleeping' Virus Enlists Merck Cancer Drug - Bloomberg: "Researchers at the University of North Carolina in Chapel Hill plan to test Merck’s drug, Zolinza, next year in about 20 people infected with HIV, the AIDS virus. The goal is to determine if Zolinza, or a medicine like it, can force HIV out of cells where it can reside, concealed from attack by potent antiviral treatments, said David Margolis, a professor of medicine who’s leading the research."

Specific eradication of HIV-1 from infected cultured cells

AIDS Research and Therapy: "A correlation between increase in the integration of Human Immunodeficiency virus-1 (HIV-1) cDNA and cell death was previously established. Here we show that combination of peptides that stimulate integration together with the protease inhibitor Ro 31-8959 caused apoptotic cell death of HIV infected cells with total extermination of the virus. This combination did not have any effect on non-infected cells. Thus it appears that cell death is promoted only in the infected cells. It is our view that the results described in this work suggest a novel approach to specifically promote death of HIV-1 infected cells and thus may eventually be developed into a new and general anti-viral therapy." [full text free]

Vienna Cure Report from Project Inform

One of the standing-room-only sessions on HIV cure research at the Vienna AIDS Conference. There were also dozens of people watching the session on a closed-circuit TV set up outside the door. Photo Credit: AIDS Policy Project

We are inviting a few guest bloggers who are also interested in AIDS cure research to post on our Cure Blog. Matt Sharp, a longtime AIDS activist, is the first. --Kate Krauss, AIDS Policy Project

The road to a cure for HIV, by Matt Sharp

There continues to be excitement and buzz especially in the research community regarding more understanding of the pathway to a cure for HIV. Recently, an NIH collaborative grant for cure research named in honor of Martin Delaney was announced that will provide even more federal dollars to the effort—though not enough. Advocates are scaling up their knowledge and working with the important players to lead to the most direct research path to a cure. There was an exciting workshop before the Vienna conference entitled: Towards a Cure: HIV Reservoirs and Strategies to Control Them. And while the efforts are moving in the right direction, there is a way to go to unlocking critical basic scientific and practical questions that scientists have long pondered, such as: Why there is residual virus and how is it causing long-term inflammation that eventually leads to the cause of most mortality seen in AIDS today? What are the biological keys to unlocking these problems? How can scientists work better together in a focused effort for a cure? How will studies ethically allow for cure research in people who are doing well?

Sharon Lewin from Monash University in Melbourne, Australia gave a succinct and motivating opening plenary speech stating that even treating the current 40% of HIV-positive people in low- and middle-income countries starting at the CD4 threshold of 200 cells would cost $25 billion by 2030, while increasing coverage to 80% would raise that cost to $35 billion. We cannot treat ourselves out of the epidemic as current cost projections and universal access and sustainability are improbable. She said that “while there won’t be a cure announced in Vienna, it will mark the future where we seriously prioritize finding a cure”.

Finding a cure is the new wave of HIV research and knowledge in this area is growing at every HIV meeting. Pharmaceutical companies have teams of scientists focusing on new drug targets and are screening millions of candidates that will flush HIV out of cells. Some two dozen HDAC inhibitors (histone deacetylase) are being studied to activate latent virus for these cells. Some of these compounds are also being studied in cancer. IL-7 can also activate cells and is moving forward in Phase 2 clinical studies. This is one area of eradication research that is moving ahead that many are not aware is happening.

Lessons are being learned from the Berlin “cure” patient who received a bone marrow transplant for lymphoma using HIV resistant cells. He remains free of HIV today. Several cell therapy strategies rendering HIV resistant by genetic manipulation are already in clinical studies.

Project Inform's full Vienna report is here.

LOYOLA RESEARCHERS ZERO IN ON PROTEIN THAT DESTROYS HIV

loyolamedicine.org: "Using a $225,000 microscope, researchers have identified the key components of a protein called TRIM5a that destroys HIV in rhesus monkeys.

"The finding could lead to new TRIM5a-based treatments that would knock out HIV in humans, said senior researcher Edward M. Campbell, PhD, of Loyola University Health System.

"Campbell and colleagues report their findings in an article featured on the cover of the Sept. 15, 2010 issue of the journal Virology, now available online."

Front Page Article on AIDS Cure Research--Go Paula Cannon!

Hey Paula--we'll call this a cure! Note that the photo was taken on July 16, 2010, when the rest of the AIDS world was at the Vienna AIDS Conference.


HIV-resistant cells work in mice. Can they help humans?
California scientists, boosted by stem cell research funding enabled by Proposition 71, are aiming for clinical trials involving gene therapy through bone marrow transplants.

Paula Cannon, a biology professor at USC's Keck School of Medicine, inspects a mouse that will be infected with HIV. (Allen J. Schaben, Los Angeles Times / July 16, 2010)

By Rachel Bernstein, Los Angeles Times

August 21, 2010|6:44pm

Clad in a yellow gown, blue foot covers, hair net, face mask and latex gloves, Paula Cannon pushed open the door to the animal room. "I hate this smell," she said, wrinkling her nose.

The stink came from scores of little white mice scurrying about in cages. Some of the cages were marked with red biohazard signs, indicating mice that had been injected with HIV.

Yet, in some of the animals — ones with a small genetic change — the virus never took hold.

Like mouse, like man? Maybe so.

In early 2007, a patient in Berlin needed a bone marrow transplant to treat his leukemia. He was also HIV positive, and his doctor had an idea: Why not use the marrow from one of the rare individuals who are naturally resistant to HIV and try to eradicate both diseases at once?

It worked. Sixty-one days after the patient's transplant, his virus levels were undetectable, and they've stayed that way.

Since news of the man's cure broke, HIV patients have been telephoning doctors to ask for bone marrow transplants. But it's not that simple. The treatment is too risky and impractical for widespread use.

"A bone marrow transplant — it's a horrible process you would not wish on your worst enemy unless they needed one to save their life," said Cannon, a biology professor at USC's Keck School of Medicine. There are grueling treatments to prepare a patient for transplant; the danger of rejecting the marrow; and the risk of graft-versus-host disease, wherein the marrow attacks the patient.

And that's assuming the patient can find a matching donor — a difficult proposition in itself — with the right HIV-resistant genetic constitution, which is present in only about 1% of the Caucasian population.

But there could be another way.

New Strategy Could Eradicate Latent HIV-Infected Cells

AIDSmeds: "Researchers report that they have taken the first step toward killing cells that are latently infected with HIV—cells that serve as a reservoir of persistent HIV reproduction and that current antiretroviral (ARV) drugs can’t reach. Their findings have been accepted by the open-access journal AIDS Research and Therapy. ...

"After two weeks of treatment with the combination, no HIV DNA could be found, and this remained the case for an additional two weeks after the last dose of the treatment was added to the cells. The authors caution it is possible that some residual integrated HIV DNA was still present in the cells. Nevertheless, their results are encouraging.

“Stimulation of viral integration by the INS and INrs peptides, combined with the prevention of virion production by the protease inhibitor, not only resulted in blocking of HIV-1 infection but also in extermination of the infected cells by invoking apoptosis,” the authors concluded.

“Whilst this research is promising, a major caveat with these studies is that they are preliminary,” Loyter cautioned. “So far these experiments have only been shown to ‘cure’ HIV from small dishes of cultured cells in the authors’ laboratory, but the findings are an exciting development in the quest to eradicate this devastating global pandemic.”a>: "Resear"

HIV Cure: Controversy, Consensus, and a Consortium

AIDS Research and Human Retroviruses: "In an address at the 2010 Conference on Retroviruses and Opportunistic Infections, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, issued a clarion call to action. Describing research toward a cure as “high risk but very high impact,” he continued: “I feel strongly that this is a direction we should go, even though years ago this would have been unimaginable.” At amfAR, we wholeheartedly concur."

"You Only Need One Talking Dog to Know that a Dog Can Talk."- Jon Cohen

So the Kaiser Foundation made videos during the Vienna AIDS Conference--videos that apparently nobody is watching. This one is with Jon Cohen, the famous Science reporter who has been covering AIDS since at least 1990. On July 19, 2010, he talks about AIDS cure research starting at 5:02 minutes in (though the first part, about global AIDS funding, is interesting too). So far, only 8 people have viewed the thing, so maybe together we can spike that number.

I attended the basic science pre-conference that he describes, and that is what I have been blogging about (and I'm not finished yet). And we at the AIDS Policy Project are excited that the organizers are going to keep having those AIDS cure basic science conferences--a big step forward in the effort to find a cure.

We're a little more optimistic than he is about the prospects for a sterilizing cure (no HIV anywhere in your body) because of the example of the Berlin Patient. As Jon himself puts it, "You only need one talking dog to know that a dog can talk."  

Our strongly held view is that researchers shouldn't start out trying to find a cheap cure; that they shouldn't tie one hand behind their backs. They should develop any safe and effective cure, first. If it turns out to be tricky to administer and expensive to produce, we will all work together to simplify it and bring down the cost and make it accessible to the masses of people--as we did for AIDS drugs in Africa. And meanwhile, other curative therapies may come along that are simpler and cheaper.

After all, a year of AIDS drugs used to cost, what? $15,000 per year in Africa, and require refrigeration. Not anymore.

What's all this about neutralizing antibodies against AIDS?

Dr. Paul Sax

There is a new video explaining the whole new "anti-HIV antibodies" discovery.

Check out Dr. Paul Sax from Brigham and Women's Hospital in Boston as he very clearly explains, in a four-minute video, all the excitement over the new research published in Science regarding HIV-neutralizing antibodies. (Science seems to be on a roll.) Researchers have discovered a man whose anti-AIDS antibodies actually kill AIDS! Unlike almost everyone else's. It's an understandingly perky and enthusiastic Paul Sax, on video in what appears to be his living room.

Thanks, Paul--super clear and helpful!

http://www.medscape.com/viewarticle/725376?src=emailthis

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).

Conference reporting from Aidsmap.com

For excellent reports see http://www.aidsmap.com/cms1374931.aspx.

Topics reported include:

Successful hepatitis C treatment reduces HIV disease progression and non-liver-related mortality 

Antiretroviral drugs have variable effects on bones and fat, lipoatrophy uncommon with modern regimens

HIV treatment may prevent at least nine out of ten transmissions

Vitamin D deficiency extremely common among HIV-positive patients in diverse regions

Maraviroc showing tantalising promise as microbicide in preclinical studies

Smoking cessation lowers cardiovascular risk in D:A:D cohort

Immune restoration in DART study: late start means low CD4 count for years

New CCR5 antagonist TBR-652 shows good antiviral activity in early study

Elvitegravir 'Quad' pill performs well, new booster cobicistat works as well as ritonavir

Risk factors for lung cancer in people with HIV: smoking vastly outweighs HIV

Goosby warns of need for long-term funding commitment for AIDS, says financial trades tax is 'interesting'

and many more.

Microblog post from Retroviruses Conference in SF

RT @jsjcroi CURE research and possibilities came up again and again in the opening press conference. After years in limbo, it is back on the agenda [!].

AIDS cure research needs your help

Bay Area Reporter Guest Opinion
Published 02/18/2010

by John S. James, Stephen J. LeBlanc, and Kate Krauss

This Saturday, February 20, the AIDS Policy Project will hold a public town hall meeting on the state of AIDS cure research, with expert HIV eradication researchers Dr. Steven Deeks of UCSF, and Dr. David Margolis of the University of North Carolina. This meeting happens right after the most important annual U.S. AIDS scientific conference, held this week in San Francisco. The town hall will take place at the API Wellness Center at 730 Polk St. (near Willow) in San Francisco, from 6 to 9 p.m. All are welcome.

The AIDS Policy Project organizes and educates activists and the community to support research for a cure for HIV. Good research is already happening, but the information often doesn't reach the world outside science circles. Today, most clinical trials test "me-too" drug combinations that will never lead to a cure – but instead create marketing claims for highly profitable pharmaceutical companies. New ideas that could be game changing always find it hard to get funding; more so now with the economic crisis.

Credible AIDS cure possibilities are being studied. (For more information on any of these, see www.aidspolicyproject.blogspot.com). CD4-cell modification approaches have received heightened interest in light of the possible cure of one American Berliner with HIV. The man had successfully controlled HIV with anti-HIV medications for several years. When he was diagnosed with relapsed leukemia, the available remaining leukemia treatment was the destruction of all of his blood's immune cells through radiation and chemotherapy and then a bone marrow transplant. His leukemia doctor, Dr. Gero Hütter, located a matching bone marrow donor who had a mutation called a double CCR5 deletion (found in about 1 percent of Europeans) that makes people immune to most HIV. The double CCR5 deletion donor cells completely replaced the patient's own immune cells in the blood – and the mutation prevented re-infection from any HIV that might have survived in the body.

This patient has been off all anti-HIV drugs for over three years, and no HIV has been found in his body. The bone-marrow transplant treatment is too difficult and dangerous to give to everybody and is generally only used in terminal cancer patients with no other options. But, it is a "proof of principle" for CD4 cell modification therapies. For example, an HIV infected person's own T-cells might be genetically modified to be made immune or resistant to HIV. One such T-cell modification treatment is being studied in clinical trials by Sangamo BioSciences Inc., some of which will be run in San Francisco.

Current anti-HIV drugs treat but do not cure AIDS because a tiny amount of HIV remains in "reservoirs" in the body, generally inside the nucleus of inactive cells, such as CD4 memory cells. Research indicates that only about 1 in 1,000,000 CD4 cells of a person on anti-HIV drugs is latently infected with HIV. Virus inside such cells is not killed by anti-HIV drugs and some of these cells live for a very long time, possibly decades. A few of these latently infected cells constantly become active as a result of the normal functioning of the immune system. So, when anti-HIV drugs are stopped, HIV infection generally restarts quickly.

Therefore, another approach to a cure is to identify drugs that selectively target infected resting CD4-cells. Once a latent HIV-infected CD4-cell is activated, research indicates that the cell dies quickly. Research also indicates that existing anti-HIV drugs might be effective enough to prevent these short-lived activated CD4-cells from infecting any new cells. However, the activating drugs may cause other, unwanted immune stimulation. Finding a therapy that can activate HIV-infected CD4-cells but not cause other harm will be challenging. It is also possible that other reservoirs of HIV may be uncovered after virus from inactive CD4-cells is purged. Margolis, at the University of North Carolina, has conducted trials with one inducing compound (valproic acid), and while this compound is, at least by itself, clearly not sufficient to do the job in most patients, work is continuing to identify better approaches to clear persistent reservoirs of HIV infection.

Other researchers are working on new scientific approaches for detecting HIV activity at levels far below the existing viral load tests. These new tests will be necessary to determine whether or how well HIV eradication therapies are working. Deeks, at UCSF, is working on one approach that measures HIV T-cell activation markers. If successful, doctors could use the markers to determine if an HIV eradication therapy has been effective without requiring a patient to repeatedly stop anti-HIV medication to see if the virus returns.

Human clinical trials aimed at curing HIV will be challenging to conduct because they may require cooperation from several different researchers or institutions that have access to different components of an effective treatment strategy. Companies don't always like to collaborate in this way because they may be asked to give up proprietary information. class=msoIns>

Also, these trials might be difficult to fill because the patients needed for enrollment will often be those who are otherwise doing very well on HIV therapy, and there may be some intrinsic risk to initial studies. However, once those barriers are overcome, HIV eradication trials could be much smaller, much faster, and much cheaper than vaccine or prevention strategy trials, which remain vitally important. A proof-of-principal HIV eradication trial might require only a few dozen to 100 enrollees, rather than the thousands that are required for vaccine trials.

Advocacy focused on HIV eradication will increase public awareness of the possibilities and encourage political support for cure research. If you want to help or just keep informed, see www.aidspolicyproject.org.

John S. James founded AIDS Treatment News, available at www.aidsnews.org. Stephen J LeBlanc is a member and Kate Krauss is director of the AIDS Policy Project, which supports advocacy for research to cure HIV. Visit www.AIDSPolicyProject.org

Reference pages: www.aidspolicyproject.org/downloads/ScienceMagazine.pdf, www.thebody.com/content/art53624.html, and www.scientificamerican.com/article.cfm?id=hiv-aids-latent-reservoir-treatment-cure

REFERENCES for "AIDS Cure Research Needs Your Help" (article that will be published Feb. 18, 2010)

For more information on several credible scientific possibilities for an HIV cure (or entirely new kind of treatment) discussed in "AIDS Cure Research Needs Your Help," see:

* The "Berlin Patient" -- the single person already cured of AIDS:
http://www.thebody.com/content/art53624.html

* How certain apes have evolved to tolerate HIV or SIV and not get sick:
http://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2009/11/siv-pathogenesis-an-immune-response-unresolved.html

* Stimulating latent HIV so that it can be killed with ordinary antiretrovirals:
http://www.scientificamerican.com/article.cfm?id=hiv-aids-latent-reservoir-treatment-cure


* Catalytic antibodies (abzymes), the technology in the Newsweek report:
http://www.uth.tmc.edu/pathology/research/circ/hivtherapyandvaccination.htm

Welcome to the Cure Blog!

Welcome to the Cure blog, where we will blog on AIDS eradication research issues.

For example, the excellent Treatment Action Group of New York has well summarized some very important recent research on nonpathogenic infection, much of it available as free full text, at http://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2009/11/siv-pathogenesis-an-immune-response-unresolved.html