Therapy Interruptus

To interrupt or not to interrupt, that is the question. Here is what we know that might help you decide.

STIs -- structured or strategic HIV treatment interruptions -- are controversial. They should be done only under a doctor's supervision because it is important to regularly monitor your T-cell counts and viral load during an interruption.

Here Are the Facts

Today, there are many clinical trials studying treatment interruptions. These studies are trying to find ways to help people who are in three very different kinds of situations:

1. Interruptions may be used when all drugs are failing. Carefully monitored interruptions might give old medicines a new life to fight the virus.

2. Interruptions may be used for people who are doing well with their therapy. The goal of these interruptions is to jump-start the person's immune system. This method may offer protection from drug failure. It may also allow a person to safely take a longer drug holiday. Occasionally, these particular studies also use vaccines and/or other immune-based therapies (like IL-2).

3. Interruptions may be used for people who need relief from drug toxicities. In these studies intermittent interruptions are being attempted on people who are doing very well with their medicines to see if a safe, but less toxic, way of taking drugs can be found. Some people hope these interruptions may also lead to better compliance and that this method may help resource-poor countries treat more people.

Studies Show Good News and Bad News

A current NIH study of eight people, using intermittent interruptions, is showing promise. Volunteers began taking their medicines every other week, seven days on, seven days off.

Every volunteer in this group has been doing this for at least 48 weeks, the longest for 80 weeks. So far, no one has lost control of the virus. Their viral load tests show that during the interruptions, the amount of virus stays undetectable or has a small blip, similar to what happens when people take their medicines all the time. An extremely careful look at their virus shows that, as far as anyone can tell, it is not becoming resistant to the drugs at all.

The data also shows the people in this study are experiencing decreased side effects. People in this experiment had 75% lower triglyceride levels and 15-20% lower cholesterol levels, about as good as drugs which lower cholesterol can do.

This is great news, but the study is too small to generalize to everyone.

Another NIH study shows long treatment interruptions may be dangerous for some people. In this study, some volunteers who took long interruptions before going back on drugs developed resistant virus. This depended on what drugs they were taking.

The class of drugs called NNRTIs, like viramune or sustiva, hang around a long time in the blood and the virus can become resistant easily to this class of drugs. So during long interruptions, a few people taking sustiva developed virus that was resistant to sustiva. So it seems NNRTIs are bad candidates for STIs.

People taking long STIs are also showing virus resistant to 3TC (epivir) as well, perhaps because 3TC hangs around in cells for a long time, and also is pretty easy to become resistant to.

Since it is very important to catch the development of resistance very early so something can be done to protect a volunteer, taking drug holidays outside of a clinical trial is not very smart. And if you DO do it, don't be on sustiva, viramune, or be depending on 3TC.

On the Horizon

Many new studies of STIs are starting; goals for these studies include:

• Using HIV vaccines and STIs to help the immune system fight HIV better.

• Treating people with antiretroviral drugs right after getting infected, then using interruptions or vaccines plus interruptions as a way to get the body to hold down HIV without any drugs.

• Larger studies of one week on, one week off treatment interruptions to detoxify and see if everyone can use this technique.

So, if you are intent on taking a holiday, get medical guidance, and, if at all possible, join a trial! It would be safer for you, and we all would benefit by learning about your experience. But please, don't take a holiday on your own!

Dr. Mark Dybul, NIAID, National Institutes of Health, reviewed and commented on this article.