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"