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Some clinicians feel that
once-daily regimens will mean that patients will have better
adherence to medication. After all, patients will have to
remember to take drugs fewer times each day. This may also
translate to fewer “reminders” that the patient has a very
serious disease, and therefore be emotionally very valuable
to the success of therapy.
However, it is important
to note that poor adherence cannot be fixed by the availability
of once-daily dosing. Adherence becomes even more critical
as each dose becomes more important. A missed dose of a once-daily
dose will leave a 24-hour period for HIV to replicate before
the next dose is taken, and resistance may form. Missing three
doses per month on a twice-daily regimen means that you had
95% compliance. This is the number that most experts agree
is critical for success with treatment. If one were to miss
three doses per month in a once-daily regimen, this would
translate into less than optimal drug levels and possible
drug failure. That is less than once each week and pretty
tough to accomplish for anyone!
Failing to remember a once-daily
dose will have long-term effects if resistance occurs. Probably
more important is the fact that future treatments options
may be limited if once-daily regimens are not adhered to.
Drug resistance is the most important factor in how long drugs
will work to keep viral replication suppressed. Before committing
to a once-daily regimen, we have to ask ourselves which regimen
will be most effective in keeping the virus undetectable for
the longest period of time. The once-daily convenience would
be nice, but what is more important to you? Will there really
be that much of a difference in your lifestyle going from
a twice-daily combo to a once-daily regimen, that may require
two dosing times every day anyway?
The most interesting data
about adherence is the studies that have been done in prisons
with DOT (Directly Observed Therapy). DOT is when each dose
of drug is given directly to a patient at the prescribed time
and a clinician observes the drug being ingested. In some
studies, 100% of patients using DOT for therapy are undetectable
after one year. In the same study where patients are allowed
to take the medication without an observer (self-reported
adherence), less than 80% of these people got to undetectable
in the same amount of time. Adherence is a major factor in
the success of any combination therapy.
Advertising can be a tease
and also a little misleading. Because prior use of HIV therapies
can impact which drugs an individual can use, once-daily drugs
are not for everyone, no matter how much a person would like
to have them. Even patients never having taken drugs for HIV
can have resistance to some drugs, and therefore not be able
to take advantage of some of the “easier” drugs.
I also would question each
person’s commitment to adherence, especially someone just
starting on therapy for the first time. In my experience,
the people who do better on once-daily drugs are those who
were doing well on adherence to twice and three times daily
regimens. If someone cannot adhere well to Trizivir twice
daily, how will they do on a once-daily regimen? Remember
that not all once-a-day drugs can be taken at the same time,
so it is very possible that there may be two or three dosing
events within the day. Timing of food is still important.
For example, Videx and Videx-EC and the Sustiva 600 mg tablets
are taken on an empty stomach, while Viread is taken with
food. All are once-a-day medications.
We do have a few drugs that
already approved for use as a single daily dose. Sustiva is
somewhat forgiving about the timing of the doses because of
its long half-life (the amount of time the drug stays in the
blood). Other drugs like Ziagen and even Retrovir (AZT) are
being studied to be used in a once-daily regimen. Until we
know conclusively that these combos are workable, we have
to take a wait-and-see attitude.
Once-daily regimens can offer
great hope and benefit to those who are able to take advantage
of them. We cannot forget that these are still potent drugs
and must be taken correctly for maximum benefit. All aspects
of an HIV regimen should be considered seriously, not just
the number of pills or dosing times per day. Each available
drug has advantages and disadvantages and the choice of which
combination to choose must be evaluated on potency, durability,
and resistance in addition to pill burden, side effects and
the patient’s ability to tolerate the drugs.
Glen Pietrandoni is director
of Clinical Pharmacy Services for the Walgreens Specialty
Pharmacy, focusing on HIV, located in the Howard Brown Health
Center of Chicago. Contact: Glen.Pietrandoni@walgreens.com.
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