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.
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
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
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
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
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
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 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
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
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
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