Breaking Barriers to Medication Adherence in HIV: An Interview With Robert Gross, MD

Robert Gross, MD; Shira Berman


August 05, 2013

In This Article

Less Is Not Necessarily More

Medscape: What about things we thought might work but don't? In one presentation from the meeting, they showed that less frequent, intermittent dosing does not necessarily lead to better adherence in patients on preexposure prophylactic antiretroviral medication.[2] This seems almost counterintuitive; you would think that a regimen that requires fewer doses would be easier to adhere to.

Dr. Gross: Yes, it is counterintuitive, but we've learned a lot about medication adherence and can now understand why fewer doses might not always be better.

It seems relatively clear that more than 1 dose per day is a relative barrier to adherence, and 1 dose per day is preferred over more doses per day. But fewer doses per week may not be an improvement over a daily dose because of the way a patient's daily cycle functions -- doing something 3 times a week may be harder to remember than something you do daily.

If you are self-administering something once a week or once a month, it's not necessarily better than a once-a-day administration because you've lost that reminder system that goes along with a routine: "Every day I brush my teeth, every day I eat breakfast, every day I take my medication." There aren't too many things that we do weekly that we can link to. This is an issue that will come up as we develop longer-acting drugs, and it's not at all clear that less frequent self-administered dosing will improve adherence.

What does seem likely is that if dosing is less frequent, such as once a week or once a month, and it is self-administered, you can build interventions that are more intensive than interventions that would need to be delivered every day. Because they are delivered so infrequently, more intensive interventions might hold more promise of being cost-effective, implementable, and scalable than they would be if we were trying to target more frequent dosing.

And, in fact, this may turn out to be necessary when it comes to longer-acting drugs that are taken less frequently. For a drug for which the dosing is near its half-life, any one missed dose may be more damaging. Let's say you are on a once-weekly treatment. Your adherence rate might need to be 90% in order for that treatment to work; but if you are on a daily treatment, it might be that only an 80% adherence rate is needed. The daily schedule allows for more missed doses because of how drug dosing is related to the pharmacokinetics. There is no simple answer here; an optimal dosing schedule for each drug is ultimately going to be related to the potency of the drug, its pharmacokinetics and pharmacodynamics, and the adherence rate.