Advertisement
The Body: The Complete HIV/AIDS Resource
Follow Us Follow Us on Facebook Follow Us on Twitter Download Our App
Professionals >> Visit The Body PROThe Body en Espanol
  
  • Email Email
  • Printable Single-Page Print-Friendly
  • Glossary Glossary

Sick of Taking Your Medicines? Hang in There, Help Is on the Way

May 2000

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Originally, it was hoped that HAART would lead to eradication of HIV. We are now much less convinced that this will be possible. Side effects may limit the length of time a person can keep taking the medicines, and are affecting many people's quality of life. These side effects have led to difficulties with compliance, and eventual loss of control of the virus.

Because of these problems, there is evidence that people are taking unsupervised drug holidays, and there is also statistical evidence of drug failures that may reflect lack of compliance associated with side effects.

Scientists and doctors around the world are looking at better ways to use our drugs. One of these is taking structured and supervised "drug holidays" that may not only be safe but also may help your body's immune system kick in and fight HIV by itself.

The method is known as STI or Structured Treatment Interruption -- a fancy way of saying a planned and doctor-supervised drug holiday. Please do not try this at home.

Advertisement
Enough has been discovered to give us hope that a way can be found to safely interrupt the endless drug cocktails that have worked so well for so many but which have serious, often toxic, side effects.

For those of us in the northern hemisphere (like the USA and Europe) which tends to have more money, the objective of STI is to lengthen the lifespan of our antiviral cocktails, stretching out the time until resistance emerges and allow the body an opportunity to recover from the side effects of the medications. In the southern hemisphere, where there are the poorer countries, STI represents hope that there may be a way to use antivirals that folks can afford.


What do we know so far?

For the most part there is general agreement, and lots of data, showing that if you stop taking your medicines, HIV comes back. HAART (highly active antiretroviral therapy) is a very effective therapy for HIV infection, but it is not yet a cure. However, there is new evidence from many small studies that some people are able to stop taking their cocktails and control the virus without drugs for some period of time. Enough people in small studies have interrupted therapy for us to reach some tentative conclusions:

  1. Virtually everyone who interrupts their therapy, if they are successfully suppressing HIV when they are on drugs, can successfully get back on the drugs, and the level of virus in the blood once again becomes undetectable.

  2. There has been some indication that some people who have interrupted therapy have not been able to get their T-cells back up to the level that they were prior to the interruption. For this reason, we need to say at the outset that NOBODY should be stopping his or her therapy out of the context of a study!

  3. Enough people are able to contain HIV without the use of drugs for long enough periods of time to make it important for the scientific community to learn why this happens and who is able to do it.
For these reasons a series of studies have begun across the United States and Europe of Structured Treatment Interruptions (STI). Some of these studies alternate Immune-Based Therapies (IBT) during the period of time that HAART is interrupted. Immune-based therapies are therapies that attempt to strengthen the immune system's efforts to fight HIV. Two examples of IBT are IL-2, and Remune.

At Massachusetts General Hospital, Dr. Eric Rosenberg is beginning a study of STI in chronically infected people, having conducted a series of interruptions among recently infected people with significant success. Dr. Kendall Smith at the New York Presbyterian Cornell Medical Center has been using low-dose interleukin 2 (IL-2) to boost the immune system when antiviral drugs are withdrawn. As these studies begin to provide us with data, we will be increasingly able to identify what methods work for which people.


The Theory

It has been known for a long time that some people can control HIV without help from drugs. These people are called long-term non-progressors (LTNPs). There are three apparent reasons why LTNPs can keep HIV under control without the help of powerful antivirals.

  1. Some people have a type of virus that is very slow.

  2. Some people are born without a kind of "receptor" on their cells making it very difficult for the virus to get inside of their cells.

  3. Most LTNPs, however, have only one thing in common: unlike people who progress, their soldier cells (both T-cells and natural killer cells) attack HIV-infected cells aggressively. Most people with HIV have sluggish soldier cells as if they did not recognize HIV as an enemy. For this reason, the late Jonas Salk called HIV illness the, "Alzheimer's of the immune system."

Drs. Bruce Walker and Eric Rosenberg from Massachusetts General Hospital have tried to understand how to make a person with HIV into a long-term non-progressor. They began by identifying people who had been recently infected and then immediately gave them powerful antivirals. This protected their soldier cells and as a result, these people looked a lot like LTNPs. In fact, after stopping antiviral therapy, these people seem to be able to control the virus for long periods of time without drugs.

The next step for scientists is to see if there is a way to cause people who did not take antivirals immediately after getting infected to look like long-term non-progressors. There are three ways this is being attempted, with many variations:

  1. using HIV vaccines

  2. using IL-2, which may increase the number of the killer soldier cells and help them fight better

  3. through interrupting therapy repeatedly in an attempt to "immunize" the soldiers with a person's own virus.


Why HIV Vaccines?

If HIV is the "Alzheimer's of the immune system," then it makes sense to try to get back the memory. And now there is evidence that an HIV vaccine can increase the number of new soldier cells that can recognize and fight HIV.

There is a test to measure whether or not soldiers are recognizing HIV as an enemy. Dr. Fred Valentine at New York University Center For AIDS Research, has done a study of an HIV vaccine called Remune: he got a group of HIV+ people taking HAART and administered the real vaccine to half and a placebo to the rest. Those who got the real HIV vaccine, acquired soldiers that fight HIV just like the long-term non-progressors and those who did not get the vaccine did not have soldiers that fight HIV. This means that we may be able to increase the number of soldiers born after drugs control the virus that have the capacity to recognize and fight HIV.


IL-2

Another method that might be helpful in trying to control HIV without drugs is to get the soldier cells to behave properly. Whatever HIV does to make the soldier cells work poorly might be reversed if we understood why they don't work well. Some people think that IL-2 might do this. There is some evidence that this might be so, and there will be a study of this in New York City. In fact, there are several things that IL-2 seems to do that might help the immune system. For one thing, it increases the number of soldiers by a huge amount. T-cell levels often go up to normal when using this chemical messenger that tells T-cells to make copies of themselves.

Dr. Kendall Smith, who is at Cornell University Medical Center, has been studying the effect of low, daily doses of IL-2 given after HAART has been discontinued, and has found that IL-2 promotes a marked increase in killer T-cells that then function to control the virus. A new trial planned at the Cornell Medical Center will test the combination of IL-2 and HIV vaccination while people are on HAART, followed by treatment interruption to see whether the viral relapse can be prevented.


Try it All

A few trials are trying to combine methods. These studies involve four steps:

  1. using HAART (powerful combinations of antivirals) which suppress the virus. Expected result -- new soldier cells start to grow.

  2. using a vaccine to increase the number of new soldier cells that recognize and fight HIV.

  3. using IL-2 to further increase the number of new soldier cells and repair cell dysfunction.

  4. using a series of treatment interruptions so the virus comes back a little bit, causing a further increase in the number of new soldier cells which recognize and fight HIV.
It is important in these interruptions to make sure that the amount of virus that comes back is not allowed to overwhelm the new soldier cells, so the amount of virus must be measured very often, sometimes daily, and then when there is too much virus, push it down with antivirals again until more soldier cells are born ready to fight HIV.

The hope is that over time this will lead to the body's soldier cells being able to contain the virus without constant help from antivirals. This is very important since the most serious thing limiting how long the new drug cocktails will work, might well be the side effects. It makes sense that anything that allows for strategically planned interruptions in using the drugs, allows the body the opportunity to recover from those toxicities. In this regard, it is important to realize that the toxicities of the antiviral drugs can be severe, and in some cases may be irreversible. Therefore, indefinite therapy with the antivirals may be unrealistic.


Don't do it on your own!

We hope that we can find a way over the next few years to get off of drug cocktails using STI and IBT. What you should NOT do is try out any of these methods on your own. Join a study so you will be carefully and safely monitored and everyone will benefit from your efforts. Or at very least, make sure you are stopping therapy or using IBT under the supervision of a doctor.

If we can learn how to use STI and immune boosters correctly, not only do we all benefit from lower toxicities, longer lifespans for our cocktails, and the possibility for some of us to stay off drugs for long periods of time -- we also perfect a method of using our medicines that might be inexpensive enough for the rest of the world to afford the cocktails we use.



David Scondras is the founder and chairman of Search For A Cure. Scondras developed the nationally recognized HIV treatment series, Reasons for Hope. All articles in the series are reviewed by expert HIV doctors and scientists and an HIV positive and negative focus group to ensure both accuracy and understandability.

Community reviewers include: Matthew Daloisio, Stuart Pynn, Dede Ketover and Robert Krebs.

The Scientific Review Panel for this article includes: Dr. Alfred DeMaria, Massachusetts Department of Public Health; Dr. Kendall Smith of Cornell University Medical Center, Dr. Ronald Mitsuyasu of UCLA, and Dr. Fred Valentine of New York University Center For AIDS Research.

If you have any questions or would like to receive the Reasons For Hope series, contact Search For A Cure at 34 Edgerly Road #1, Boston, MA 02115 or call Search For A Cure at 617-536-2474 or fax 617-266-0051, or e-mail at hope@sfac.org. Visit our Web site at www.searchforacure.org

Search For A Cure is a not for profit organization providing education, promoting access & advocating the basic human right to safe and effective treatment for all people living with AIDS.

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!



  
  • Email Email
  • Printable Single-Page Print-Friendly
  • Glossary Glossary

This article was provided by Search for a Cure. It is a part of the publication Reasons for Hope.
 
See Also
More on Immune-Based Therapies: Basics

Tools
 

Advertisement