Once Again, One a Day
Once-daily drugs are now more widely available to treat HIV. This has been a dream of those people forced to schedule their days around timing of the doses of drugs and food in order to maximize the benefit of the life-saving compounds. It is obvious that we all want simpler regimens with fewer side effects, but we also need to feel confident that we are making the correct clinical choices for today and the future.
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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