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Intolerant, Resistant
But Still Complying!

Summer 1997

The last thing I see every night before I close my eyes to go to sleep is a bottle of Crixivan. I swallow a couple of pills and try to ignore the burning sensation creeping up through my chest as I lay my head down on the pillow. I think my last thought for the day: At least, no one can call me "non-compliant".

The next morning the alarm wakes me up at eight and the first thing I see is the bottle of Crixivan. I swallow two more pills with the half glass of water leftover from last night and I get up. I know at 4 pm my wrist alarm will go off, screaming for two more pills, yet, I look forward to living one more day. A day of a compliance.

Monotonous and sometimes painful, the truth is that the triple drug combination I take is improving my health. Two years ago it was going down hill with no brakes. I now have more energy, more T-cells and more weight. I have a new job and have regained some control over my own life. (Instead of letting HIV control it). I feel healthier and happier.

But, even though I am compliant, I know that other things may still go wrong. The threat of intolerance and resistance is still lurking around me and every other person on triple-combo.

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By intolerance I don't mean a new form of prejudice, (we already go through enough of that!) And resistance doesn't mean that we are stubborn people. In addition to difficulty in adhering to a rigid regimen of medications, (commonly referred to as non-compliance), intolerance and resistance, are the two main reasons why antiviral therapies fail.


Intolerance

The drugs used to combat HIV, called anti-virals, are strong, toxic chemicals that may provoke side effects. Some people will not experience any side effects. Some will experience mild but tolerable side effects. Others may experience side effects so intense that the results can't be tolerated. This last case is called intolerance to the medication.

If you feel no side effects, that's great. You have the best chance of getting the most out of the medications. Your doctor must still continue checking your lab work to make sure that no hidden side effects will go unnoticed. (Such as anemia and liver or kidney malfunction).

Mild side effects may be better tolerated with some help from your doctor who can prescribe remedies that will minimize the symptoms. Alternative therapies, such as acupuncture, acupressure, herbs and vitamins, are important tools that make side effects more tolerable.

We all try our best to stay on the medication regimen of our choice because there is a limited number of possible drug combinations. Every time we change medications we may be eliminating one more possibility for a future therapy.

When side effects are intolerable, the doctor must help you find a different drug combination excluding the drug or drugs, that caused the intolerable side effects.

It is not your fault if you are intolerant to a certain medication. It's the high toxicity of the antiviral drugs that is the cause of the intolerance. Therefore, even healthy and compliant patients will not be able to take some drugs. (Did you read the excellent article written by Pat Rolands in the last issue of Women Alive? Her experience is a good example of intolerable side effects.)


Resistance

Antiviral drugs work by suppressing, or inhibiting, substances that the virus needs to replicate in our bodies. When the drugs are working properly, the virus can't find those substances and it becomes unable to replicate. As fewer new viruses are produced, the amount of virus in your body also reduces. You know it's happening when your viral load test shows the level of virus in your blood stream going down. ("undetectable" is the desired effect ).

HIV, however, has a high capability of mutation. Mutation means that a new generation of virus produced in your body may be slightly different than the original. And the difference may be the capability of replication even in the presence of the antiviral drug you've been taking.

When that happens, resistance has occurred. One sign of resistance is a sudden and sustained increase in your viral load.

We all have heard people saying things as: I'm resistant to AZT or I'm resistant to Saquinavir. That shows some confusion about what resistance means. It's the virus that becomes resistant to the drugs, not the person.


The Cockroach Effect

There are some known factors that may result in drug resistant virus. We now know that a virus that has been treated with a single drug (monotherapy) will quickly develop resistance to that drug. That's why monotherapy is not recommended anymore. The current way to fight HIV is using at least three drugs (the so called "cocktail"). It takes one step for HIV to create resistance to one drug. It takes a triple step for HIV to create resistance to three drugs at the same time. Three drugs together have a better chance of delaying that mutation.

Many medications, if not taken in the right dosage, can also lead to mutation of the virus. It's the cockroach effect. Throughout history man has been using different poisons to kill roaches. The surviving bugs create a defense against that poison and the descendants of those bugs don't mind it at all. A new poison is used and a new cycle starts. The result is a strong, fortified super-roach that will survive mankind even in the event of a nuclear war.

With HIV a similar process takes place. A medicine taken in too small a dosage to control the entire infection, even if taken in a three drug regimen, will yield to the production of a new strain of virus that won't be affected by that drug any longer. That's why it is so important to take the medicines in the prescribed dosages, minimizing the chances for the virus to mutate.

Besides the possibility of HIV mutating in your body, there is also a chance that the virus you have was previously resistant to one or more drugs. This happens when the virus you were infected with has been exposed to antiviral drugs taken by the person or persons who had it before you. In the late 80's and early 90's it was considered standard therapy to treat HIV with a single drug. Remember, for a long time all we had was AZT. By treating people with only one drug, a new resistant breed of the virus emerged and it can theoretically be transmitted in subsequent infections.

There are some tests that may tell you if your virus is already resistant to some drugs, but these tests are not yet widely available. Activists are now pushing companies to develop and market more of these kinds of tests.

The more drugs the virus in your body is resistant to, the fewer drugs will be effective against the infection. So you will have fewer options left of drugs to compose a drug regimen that works for you. Although new drugs are coming out all the time, (Glaxo Welcome's 1592, for example is going to be rationed) there is still a limited number of drugs to choose from. We must try to extend their benefits by minimizing resistance.


Non-Compliance

Compliance has become an important issue after the advent of protease inhibitors. Before Invirase, Norvir, Crixivan and Viracept, we almost never heard about non-compliance.

This is because these drugs only remain effective in your body for a limited number of hours.

For example: It is known that Crixivan remains active for ten hours, at the most. It's best performance is for 8 hours only. That's why the recommended dosage must be taken 8 hours apart. If I woke up in the morning and instead of promptly swallowing those two pills I decided to take a day off, what would happen? Within two hours the remaining Crixivan in my body would lose its effect and the virus would immediately start replicating. Those new copies would be, you guessed right, resistant to Crixivan and soon enough I would have to change my entire drug regimen. (Changing only one drug within the cocktail could also cause resistance).

Since my virus is already resistant to AZT, ddC and Invirase, and I can't tolerate ddI, Delavirdine and Norvir, there are not many options of new combinations left for me to try. Adding insult to the aggravation, I would also be called "non-compliant".

Taking a triple-drug therapy will be most helpful to you, if you take your pills at the prescribed time, every day, without fail. If you don't follow this rigid rule of "not skipping doses" of your drugs, you could actually be helping the virus to breed into a stronger, more defiant super-virus. This is just like the cockroach effect.


Access

As patients, it is important for us to do all we can to improve drug efficacy. As activists, we must demand that drug companies come up with medications that are less toxic, more effective, and easier to take, with fewer side effects. (Wouldn't it be nice to take only one tablet a day, without choking or being nauseated?)

We need widespread access to all AIDS drugs, not the unethical rationing life-prolonging drugs to a few hand-picked individuals. New medications are needed to expand the choices for those who have exhausted the possibilities available in the present market.

In the meantime, like so many others, I'll continue going to bed and awakening with my bottle of Crixivan. At least until I become intolerant or my virus gets resistant. Then I'll think of what to do.



  
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This article was provided by Women Alive. It is a part of the publication Women Alive Newsletter.
 
See Also
6 Reasons Why People Skip Their HIV Meds
Word on the Street: Advice on Adhering to HIV Treatment
More Personal Accounts of Staying Adherent to HIV/AIDS Medications
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