ju st o u t ▼ a u g u s t 1. 1 9 9 7 T 13
REASONS FOR HOPE
Path to success
he arrival of protease inhibitors has
ushered in a new era of treatment and
hope for people with HIV disease, and
even for those who have progressed to
A few
AIDS. While the majority of people
using combinations of antivirals with a protease
inhibitor are doing very well, a significant minor
ity fails with this type of treatment. Sometimes
the virus is already resistant to the medication;
other times the treatment is just not powerful
T
important steps can minimize the risk of failure
with combination antiviral therapies
▼
by The Boston AIDS Writers Group
The use and dosages of experimental com
binations of drugs should be carefully consid
ered by both you and your doctor. This is
especially true of combinations including pro
tease inhibitors and non-nucleoside reverse tran
scriptase inhibitors, for example nevirapine
(Viramune) or delavirdine (Rescriptor).
Experimental therapies are just that, experi
mental, and as such involve risks. While some
new combinations (including the ones mentioned
above) show great promise, they may also involve
serious pitfalls such as an increase in side effects
and unforeseen changes in the effectiveness of the
drugs. For people who have failed a standard
triple combination, or who have already used up
most of the nukes now available, these combina
tions may be the answer, but it is important that
your doctor understand and explain how these
drugs interact with each other.
►
enough to reduce the viral load (the amount of
virus in the bloodstream) to a low enough level to
prevent resistance from occurring. In some cases
the drugs produce intolerable side effects or are
not used as directed. In fact most, but not all, cases
of treatment failure can be attributed to one of
these causes.
For most people the critical issue is to prevent
the development of a viral strain that is resistant to
the combination of drugs they are on. Resistance
can develop because the virus sometimes makes
imperfect copies of itself when reproducing, and
some of these copies may be able to survive and
reproduce despite the antiviral combination. When
a resistant virus emerges, it may make enough
copies that the drugs begin to fail. This article
outlines steps one can take to minimize the possi
bility of that happening, and addresses some
options for people who are unable to tolerate a
given combination.
By following these essential guidelines and
working closely with adoctor who has significant
experience with HIV disease, you can get the
most out of the current treatment technology.
The goal of antiviral therapy is to get rid of
all virus in the body or at least reduce viral load
as much as possible—preferably to levels that
scientists cannot detect with the most sensitive
viral load tests available, which measure as low as
400 or 500 copies of the virus.
The fewer virus copies that are in the blood
stream, the lower the chance that they will mutate
and become resistant to the antiviral combination
you are using. It is believed that the only way to
be sure that no resistant strain will emerge is to
prevent any virus from reproducing. Currently it
is not possible to know when that happens, but
getting viral load down as low as possible is the
next best thing.
The fact that an undetectable viral load is not
necessarily the same as no virus is just one of a
number of reasons why it is as important as ever
to practice safer sex.
Know what your viral load is when begin
ning a new combination. This is important for
two reasons. First, to make sure the drug is work
ing. You will want to check your viral load later
and compare it to your starting point. Second, you
need to consider if the combination you are plan
ning to take is strong enough to get your viral load
down to undetectable levels. People with very
high viral loads may want to consider something
more powerful than a standard triple combination
of a protease inhibitor and two nucleoside ana
logues (nukes).
All drugs must be taken as directed by your
doctor and pharmacist. Now that researchers
understand how and why resistance occurs, they
are insisting that skipping doses (or even taking
lower doses) can lead to viral resistance and then
to drug failure. For this reason it is imperative that
you are prepared to make a commitment to the
treatment regimen of your choice. If you falter
and miss a few doses, it is probably a good idea to
find a dependable alarm-type device to remind
you to take your medicine each day. Also, under
stand that if you miss taking a dose of an antiviral,
resistant, and makes that drug useless to you in the
future. When beginning a combination that in
cludes a protease inhibitor, it is best to start out
with antivirals that you’ve never used before. If
there are no antivirals (nukes) that you have not
used before, consider using a double protease
inhibitor combi nation like ritonavir and saquinavir
or a combination including both a protease inhibi
tor and a non-nucleoside reverse transcriptase
inhibitor (non-nuke).
Don’t panic if you make a mistake. While it
is important not to miss many doses of your
medication, it is unlikely (though not impossible)
that one missed dose will lead to drug failure.
Don’t let one mistake unnerve you to the point that
you make more mistakes, or stop the therapy. If
you find that you are often missing doses, or that
you avoid taking one or two of the drugs in your
combination, you should consult with your doctor
about whether or not you should continue to use
this combination given the increased possibility
of the drugs failing.
taking it late is better than skipping it completely.
Powerful antiviral combinations provide strong
pressure to stop the virus from reproducing. Any
let-up due to low drug levels gives the virus a
chance to mutate and eventually become resistant
to the therapy.
gerous side effects. For this reason you need to be
open with your doctor about the other drugs you
might be taking. Your pharmacist can be espe
cially helpful in this area.
Store your medications properly, especially
protease inhibitors. Indinavir must always be
stored in its original specially coated bottle or the
drug will quickly decay. The capsule formulation
of ritonavir must be refrigerated at all times or it
also will decay. When calling in your ritonavir
prescription to the drugstore, it can’t hurt to
remind your pharmacist to continue to refrigerate
it until you pick it up. Improper storage can affect
the strength of the drug and lead to drug failure.
When using a protease inhibitor, timing
meals around dosing is very important. Be
sure to follow all label directions, including
those regarding meals and side effects. Differ
ent drugs are absorbed differently by the body.
Instructions around meals are given so that enough
of the drug gets into the bloodstream. Taking the
drugs without paying attention to meals may
mean that the body is getting too low a dose, and
like skipping doses, that can lead to resistance.
The protease inhibitors ritonavir (Norvir) and
saquinavir (Invirase) should be taken after eating
fatty foods. Nelfinavir(Viracept) should be taken
with food, while indinavir (Crixivan) should be
taken on an empty stomach.
It is also very important to watch out for side
effects and report them to your doctor. Recently
high blood sugar levels was added to the list of
possible side effects of protease inhibitors.
Protease inhibitors should generally be used
with at least two other antivirals. Each drug
used sets up a different roadblock for the virus to
get around if it is to successfully reproduce. Using
more antivirals makes it less likely that the virus
will mutate to a form that can get past all the
roadblocks. Furthermore, the fewer virus copies
that reproduce, the less likely it is for them to.
mutate and become resistant to your antiviral
combination.
Do not take any drugs not prescribed to
you, over the counter or recreational, without
first talking to your doctor. There are many
drugs that can interfere with the effectiveness of
HIV antivirals.
Taking antivirals with other drugs can affect
the level of medicine in your body. Therefore
taking the wrong types of drugs with your treat
ment regimen can lead to drug failure or to dan-
Do not add an antiviral to an existing drug
regimen that is failing or may have already lost
some of its benefit. Although this is true of any
antiviral, it is especially important in regard to
protease inhibitors.
If you add a protease inhibitor to a combina
tion that isn’t working at its full potential, it is
similar to using the protease inhibitor all by itself.
This makes it much easier for the virus to become
There may be bumps in the road. Of course,
these guidelines are for people who are regularly
taking a combination. For others there may be a
more basic problem: that they cannot tolerate a
drug because of its side effects. This is not to be
taken lightly; some side effects can be very seri
ous, and some (such as vomiting or diarrhea) can
prevent the drugs from workingeffectively. Ifyou
cannot tolerate the combination you are on, con
sider the following:
Bad side effects may be temporary. For ex
ample, many people who take ritonavir report that
after one month or so, many of their bad symp
toms get better or go away.
You can change the drug causing the problem
to another drug of a similar type. Many people
have used this route successfully, and there are not
any obvious dangers in switching as long as an
extremely low viral load is maintained. However,
it is possible that some method of reducing the
impact of side effects is wiser than trying to
change therapies. Additional drugs, including some
over-the-counter drugs can alleviate side effects,
and changes in diet have reportedly helped many
people deal with nausea. Just because you can’t
tolerate a given combination doesn’t mean you
can’t find one that you can tolerate.
Finally, if two viral load tests in a row show
that your combination is failing, if at all possible
you should consider changing to a new regime. As
more drugs become available this will be an
option for increasing numbers of people, and it is
truly the best way to ensure that your therapy will
work for you.
The Boston AIDS Writers Group consists o f
Robert Folan and Lou Pesce o f ACT UP
Boston; and David Scondras, Robert Krebs,
Derek Libby and Larry Bresslour from Search
fo r a Cure. For more information, write Search
fo r a Cure, 58 Burbank St., Boston, MA 02/15;
call (617) 536-2474; or e-mail hope@sfac.org.