CROI 2008: Boston, Massachussetts; February 3-6, 2008

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The Body PRO Covers: The 15th Conference on Retroviruses and Opportunistic Infections

Among Patients on Boosted-PI Regimens, Dose Staggering and Selective Non-Adherence to Ritonavir Is Relatively Common

An Interview With Jonathan Shuter, M.D.

February 6, 2008

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There's nothing like hearing the results of studies directly from those who actually conducted the research. It is these women and men who are transforming HIV treatment and care. In this interview, you'll meet one of these impressive HIV researchers and read an explanation of the study he is presenting at CROI 2008. The interview was conducted by Dr. Gerald Pierone, an HIV clinician/researcher and the founder and executive director of the AIDS Research and Treatment Center of the Treasure Coast in Fort Pierce, Florida.

Jonathan Shuter, M.D.
Jonathan Shuter, M.D.
I'm here with Jon Shuter of Montefiore Medical Center. Can you tell us about your research?

We enrolled and completed a study on 35 patients to look at the question of whether patients were selectively not adhering to the ritonavir [RTV, Norvir] in boosted PI regimens.1 The regimens [all contained] boosted atazanavir [ATV, Reyataz] or boosted fosamprenavir [FPV, Lexiva, Telzir]. All the patients were receiving once-a-day [therapy], except for one [boosted] fosamprenavir patient who was receiving twice-a-day therapy. We placed MEMS [Medication Event Monitoring System] caps on both bottles of the regimen.

Can you tell us what MEMS caps are?

MEMS caps are electronic monitors. They give very, very rigorous, quantitative data regarding adherence over time. These patients were followed for 24 weeks with MEMS caps on both bottles. Our finding at the end was that three out of 35 patients who completed the study were selectively non-adherent to ritonavir in these boosted regimens. We define selective non-adherence as taking 5% less; we quantitated adherence with MEMS caps and get a final number, which is a percentage of adherence. Those who took ritonavir with an adherence rate that was more than 5% lower than the adherence rate to the boosted PI -- either atazanavir or fosamprenavir -- were considered selectively non-adherent to ritonavir. We found that occurred in 9% of the patients.

We also looked at dose staggering: taking the dose of ritonavir more than four hours apart from the boosted PI dose. [Both doses] are supposed to be taken simultaneously; there might be pharmacokinetic consequences of taking them apart. We found that seven patients -- that is 20% of the population that we studied -- staggered doses more than 5% of the time.

Were your patients instructed to keep their ritonavir in the refrigerator? Did some of them do that and some not?

We didn't get involved in instructing patients one way or another. We didn't want to be an intervention; we wanted to be observers. I do know that the pharmacies that we deal with routinely put a "please refrigerate" sticker on their meds -- on their ritonavir, at least. My own clinical experience tells me that most patients keep it apart [from their other meds], in the refrigerator.

Did you find that the selective non-adherence or the staggering, although the sample size was small, translated into differences in clinical outcomes?

We did not find that. We looked at viral load at 24 weeks, and the three patients who were selectively non-adherent to ritonavir were all suppressed below 75 copies per mL. Although, as you say, the sample size was probably too small to really evaluate that in a good way.

The take-home message for clinicians?

The take-home message is that selective non-adherence to ritonavir occurs. It occurs in around 10% of patients. It's easy and quick to at least reinforce the message to [patients] that they should take these medications together and simultaneously every time.

Have you made any changes in your clinical practice as a result of this study, other than intensifying your educational message?

Other than that, no.

Have you considered using pillboxes for adherence issues in your patients?

We encourage the use of pillboxes. Obviously, that doesn't work well in a MEMS cap study. But for certain patients, pillboxes are a very valuable tool, and we do encourage their use.

There have been some studies showing better adherence with pillboxes.2 We've also found that because of that refrigeration label on ritonavir, in some cases patients have all their medications in pillboxes except the ritonavir, which is in the refrigerator.

They could put the whole thing in the refrigerator also.

Yes. Or, I suppose, they could keep everything out of the refrigerator, if they're doing a weekly pillbox. Ritonavir should remain stable despite lack of refrigeration for at least one week, probably much longer.


Thank you.

This transcript has been lightly edited for clarity.


  1. Shuter J, Rode R, Sarlo J, Zingman B. Rates of ritonavir non-adherence and dose staggering in HIV+ patients receiving RTV-boosted atazanavir or fosamprenavir. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 803.
  2. Petersen ML, Wang Y, van der Laan MJ, Guzman D, Riley E, Bangsberg DR. Pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and viral suppression: a marginal structural model analysis. Clin Infect Dis. October 1, 2007;45(7):908-915.

This article was provided by TheBodyPRO.

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