AIDS TREATMENT NEWS - July 11, 2007
David Scondras, hope@sfac.org

Summary: The c-word is coming back due to new research, after a decade of banishment.

Once again we are hearing about efforts to eradicate HIV, at least in some people. These efforts are being made, not by marginal actors, but by some of the country's top doctors, such as Anthony Fauci, longtime director of many HIV research efforts at the National Institutes of Health.

On May 24th the Bloomberg report (Bloomberg.com) headlined the issue this way:
"Top U.S. Scientist to Use New AIDS Drugs Seeking Cure" [1].

For a summary of scientists' efforts exploring the possibility of eradication, see [2].

So what happened?

For many years scientists have understood that after HIV gets into someone's body, it starts infecting lots of T-helper cells. They are sometimes called CD4+ T cells.

T-helper cells are the cells that recognize that the body has been invaded by some enemy germ. If these kinds of cells are significantly reduced, the body is unable to recognize many illnesses, which start infecting a person with HIV. This is what we call having "AIDS".

The way HIV works begins with HIV inserting instructions into these T-helper cells on how to make more HIV. These instructions are known as 'provirus'. They are kind of the brain of HIV and it is these instructions that turn the cell into a factory that can make HIV.

The number of these factories is dramatically reduced soon after an HIV-positive person takes strong HIV medications. Unfortunately the medicines we have today do not eliminate all of the provirus. If you checked the cells of people with HIV who are taking antiviral medicines, you'd see that although HIV medications have eliminated most HIV from their bloodstream, some cells with these instructions on how to manufacture HIV remain. It is still unclear why these cells containing instructions remain while most of the virus has been eliminated. The cells that have provirus but are not producing HIV are called 'latently infected'. They have the ability to spring into action at any time.

Scientists have at least two different theories that might explain why HIV in someone's body does not disappear altogether with the use of antivirals.

The first theory is that these latently infected cells can hang around for as long as twenty or thirty or forty years. As soon as someone stops taking antiviral medicines, these cells can spring into action and manufacture HIV.

The second theory is that the medicines we have been using until now do not shut off all HIV reproduction, just most of it -- and that is why when antivirals are stopped, the virus comes back.

The first theory makes us pessimistic about getting rid of HIV and curing someone infected with it.

We know that provirus does not make virus until the cell containing it is 'activated'. This means the cell is turned on by coming across footprints of a germ which cause the T cell to make proteins getting the immune system ready to fight the invader. When the T cell is manufacturing these proteins it also starts making HIV.

No one knows exactly HOW long it takes before all latently infected cells are activated.

For this reason, most scientists, doctors and activists have been very skeptical about finding a cure for HIV. Finding a cure would require getting rid of all cells that contain provirus. Unfortunately, the HIV medications we currently use do not get rid of these latently infected cells.

The second theory suggests that with more powerful drugs we might eliminate all HIV from the body.

New drugs which are in the pipeline are much more powerful than the one's we have right now. This leads us to a hopeful possibility. What if we could eliminate virtually all infected cells with the help of brand new HIV medications that are more powerful than ever before? What if the new drugs work so well that the immune system is able to get rid of the few infected cells that are left? This is the operating theory behind radiation treatments for cancer.

How can we find out which theory is correct?

First we would use the powerful new HIV medications now available -- which perhaps can shut down all HIV replication completely and then see if the body clears HIV infection.

Then, after testing to make sure no virus or provirus can be found, we would then stop using the powerful drugs and see if the virus comes back.

Sounds interesting, doesn't it? This extraordinary experiment is actually taking place right now.

Why try this now?

First, because it has been discovered that in fact latently infected cells, containing provirus, do get eliminated from the body. It is not clear why or how, but the data shows that the body does in fact get rid of these latently infected cells (provirus).

Dr. Fauci at the National Institutes of Health, whom I mentioned above, is conducting this study. His group found that in seven HIV-positive people who used strong antivirals within 4 months of being infected with HIV, there was a reduction in the amount of provirus by 50% every 4.6 months. If these results hold up, the scientists estimate that 7.7 years of the combination therapy could possibly eliminate HIV.

The second reason this study is being done now is because there are new powerful drugs such as entry inhibitors and others, which can be used to shut down viral replication, perhaps completely. Perhaps elimination of HIV would then happen faster, maybe in one year.

The experiment is underway. Patients will be dosed with the powerful new antivirals to hopefully shut down replication altogether for one year, and then they will be taken off the medication -- assuming no virus can be found -- to see if the virus comes back.

This is an experiment that needs to be done, and it's fine to hope for good results. But there are good reasons to think it will not work, and we should not raise our expectations too high. Perhaps it will work in a few unusual people -- those who are diagnosed with HIV soon after they were infected and go to the doctor and get HIV medication. Clearly we are far away from understanding how this could work for the majority of people with HIV. Perhaps it will work for a limited period of time in some people, giving them a vacation from meds. Perhaps it will succeed completely and we can look forward to a cure.

The world will be waiting to hear the results.

Note, JSJ: This article was written before publication of laboratory research on an enzyme that can target HIV in the DNA of latently infected cells [3].

References

1. http://www.bloomberg.com/apps/news?pid=20601087&sid=a.0x1mlV37Qw&refer=home

2. http://www.thebody.com:80/content/news/art41026.html

3. Sarkar I, Hauber I, Hauber J, and Buchholz F. HIV-1 Proviral DNA Excision Using an Evolved Recombinase. Science. 2007 Jun 29;316(5833):1912-5.

David Scondras is the founder of Search For A Cure. He developed the nationally recognized HIV treatment series, Reasons for Hope. All articles in the series are reviewed by expert HIV doctors & scientists as well as an HIV positive & negative focus group to ensure both accuracy and understandability. If you have any questions or would like to receive the Reasons for Hope series contact Search For A Cure at 617-945-5350 or e-mail at hope@sfac.org . Please visit our web site at http://www.searchforacure.org

2007-07-11
ATN070704

Copyright © 2007 - by John S. James. See "Permission to Copy" at: http://www.aidsnews.org/canhelp. How to help AIDS Treatment News: http://www.aidsnews.org/canhelp.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, Roche and Trimeris, and donations from users like you.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV. Always watch for outdated information. This article first appeared in 2007. This material is designed to support, not replace, the relationship that exists between you and your doctor.

Copyright ©1980, 2007. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .