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How About Clinicians for a Cure?
Nov 7, 2004

You are giving your life for your work, and I say thank you. But I think that most cliniciansd and researchers seem jaded, and leave activism for medical progress to the patients. Do you think docs could get involved in campaigning for change?We are not gonna get real progress from the big funding sources; the last thing they seem to want to do is look at this disease in a rational manner and coherently fill in the gaps in our knowledge. But a consortium of researchers-- Aids Docs for a Cure say --- would really get things going. In a way it might be easier for clinicians to get involved in this. Researchers have to depend on not rocking the boat from funding sources.

What do we mean by a cure? The chance for people infected with HIV to live in good health again.

It seems that there would be two main ways to get a cure, either change the virus or change the immune system, or both.

Most research so far has been on killing the virus. This has resulted in some progress, in the form of expensive, toxic drugs, but it is short sighted. When has medicine ever succeeded in eradicating a virus? We've won the war on some diseases, such as polio, with vaccines, but we never learned how to kill the polio virus. We can't even kill the common cold.

Doctors always say take HAART, better, less toxic medicines are coming. Or maybe some kind of treatment interruption can help, say starting when t cells reach 200 and stopping when they go up to 350, or starting early stopping when they go up to 800 and then starting again when they drop to 400. This will win some time off meds but its not a solution. What medicine is nontoxic enough to be taken daily for decades? Let's hope those medicines come along soon, but this should not be the only funding focus.

Adam Arkin et al are looking at engineering the hiv virus to attack itself. Now that is a promising area for research. But we need more than one team working on it. There are many many teams working on tiny variations of the same antiretroviral drugs.

Numerous scholars have reengineered the virus to deliver gene therapy for other diseases. Thats right, they change the AIDS virus so it won't cause AIDS but may deliver an anti cancer or anticystic fibrosis gene. Numerous scholars have reenigineered the virus so that it will infect various species of animals for testing or in order to more safely study different properties. Its time to put much more into trying to change the virus so that it will be harmless to man. There are many viruses that can live in us without causing serious problems. Maybe HIV can become one of them.

Alternatively,maybe the immune system can be changed so the virus won't damage it so badly. Efforts in this area include vaccines and gene therapy. There is lots of work now on vaccines after years of stalling. So far they don't work well. HIV mutates rapidly and specifically attacks the immune system so its hard to train the immune sytem to fight it. There should be more work on this, but maybe its the wrong approach. Maybe it would be better to train the immune system to tolerate HIV. Sound crazy? Well the sooty mangabey lives for 20 years or more with a high viral load and never gets sick because the body seems to ignore the virus. Most of the destruction of T cells in HIV seems to be due to an overly intense immune response rather than too sluggish a response. Over a certain number of years the immune system gets worn out and then the CD4 cells are gone. This is why immune suppressant drugs such as cyclosporin and prednizone sometimes help. But they have side effects. If instead we could train the body just to relax, accept the hiv as a passenger and stop overproducing CD4s we might be able to get a steady healthy number. See Feinberg, M 2002.

Also we need to look at ways to stop the apoptosis of uninfected cells. Apoptosis iswhen the cells die off on their own without being infected. HIV seems to somehow tell unifected cells to die, while keeping the infected ones alive.

The hot thing now seems to be drugs to drive HIV out of latency so HAART can fight it. Hello?! How about putting it INTO latency and keeping it there!!! Oral herpes and Epstein Barr stay latent for decades. Yes, in some people they may contribute to cancer, chronic fatigue or MS, but in most people they are relatively harmless. If we could make HIV truly latent this would be almost as good as a cure.

Gene therapy includes engineering CD4s that won't be killed so easily, and there are several current trials of this. Its not easy, but it has had some good successes. Also the cloning of CD4s and replacement of them.

If you look at the latest stuff there is lots of hope. But lots of these ideas were being tried years ago. But in small studies. The only thing that seems to get real support is variations on the same antiretroviral drugs. And even there, most of these are me-too drugs that don't represent much of an advance. Some of them are at least good to fight resistant virus but thats not even true of most.

Any clinician or researcher who is serious about helping people should try to find ways to get more studies of the alternative ways to fight HIV disease. Temporarily killing viruses is not the only way to control AIDS, maybe not even the best.

Response from Dr. Frascino

Hello,

Thank you for your comments. Since I am an HIV/AIDS physician specialist, a Board Certified Clinical Immunologist, an HIV/AIDS researcher, an HIV/AIDS advocate and activist, an HIV/AIDS philanthropist, and person cohabitating with the virus (HIV positive), I'll add a few of my own comments to yours.

In general, I think we do get what we demand. In the bleak early days of AIDS, those diagnosed typically survived no longer than a year. We demanded something anything to help. Given the grim prognosis of those days, we were pleased to see the development of AZT that extended life for about six months. We demanded more. A decade or so later, multiple other drugs followed and HAART treatment promised years of extended life. Soon we realized how difficult and toxic these therapies are in the long run. We demanded simpler therapies and that's what we got once- or twice-a-day regimens with fewer pills and fewer, although still significant, side effects.

These "improvements" have taken the pressure off the urgency of and search for a cure. However, although I agree therapies today are far superior to those a decade ago, anything less than a cure is suboptimal and unacceptable. As the arsenal of new drugs and strategies continues to grow, we must continue to ask, "Are these new therapies minor advanced or real progress toward a cure?"

Your question reminded me that even the word "cure" is often absent form the vocabulary of many HIV/AIDS advocates, activists, community leaders and scientists. I don't mean to dismiss the ongoing "minor advances," as I have certainly benefited from them, and until there's a cure, they are certainly needed and welcomed. Minor advances after all are at least advances, and advances are progress. What they are NOT, however, is enough.

So when will there be a cure for AIDS? I don't know. But I do know we get what we demand. The demand for a cure must be reinstated into our community's lexicon at all levels. As we reclaim it, we must hold our elected leaders, activists, physicians, researchers, scientists and bureaucracies that determine research priorities accountable for making it a goal. History clearly shows HIVers hold incredible power, even when the odds are stacked against us. We and our advocates have revolutionized the system that evaluates and approves new drugs and that created mechanisms for earlier access to experimental therapies. The current administration (oh lordy, did we reelect those cuckoo clocks again???) hasn't been friendly to AIDS, either for research or for programs that serve positoids. It's time to reinvigorate the quest for a cure among ourselves and inspire others who have never known a world without AIDS to realize a cure is possible!

Our history proves that a few people can make a difference. More people can make a greater difference. So what do we do right now? How do we ensure a cure will be realized today as opposed to tomorrow? This year rather than next year? I'd suggest the first step is believing that we can make a difference, finding our voice and simply trying. There is no harm in trying; there is merely the possibility of success with no downside. If we fail, we are no worse off than yesterday. Change only happens when we find the will and courage to make it happen. Join me; demand a cure today. (www.concertedeffort.org)

Dr. Bob


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