In this episode, I’ll discuss the management of antiretrovirals in critically ill patients.
Management decisions regarding antiretroviral therapies in critically ill patients are complex. Drug interactions, lack of variety of dosage forms and decreased absorption threaten to expose patients to unintended monotherapy. This can promote the emergence of resistance, even when the unintended monotherapy occurs over a period of just days.
If HIV were to become resistant to a drug or drug class, that resistance will persist forever, and a patient would be forced to switch therapies to maintain efficacy.
While there are not formal guidelines or recommendations to prevent the development of resistance in critically ill patients who take antiretrovirals, a group of authors has published some guidance in the journal Critical Care Medicine in 2018.
Three of their major points are:
Virtually, all commonly used antiretroviral drugs are only available as oral formulations. Administration by this oral route in critically ill patients can lead to subtherapeutic drug levels and lifelong antiretroviral resistance.
Crushing tablets to put them down feeding tubes presents multiple additional dimensions of unpredictable delivery and absorption…in some situations involving uncertain gastrointestinal absorption that is likely to persist over several days or more, or inability to administer oral agents even through a feeding tube, ART should be stopped altogether since the absence of drug removes the selective pressure which drives antiretroviral resistance.
Discontinuation of multidrug or single tablet regimens when the individual component drugs have different half-lives can lead to periods when only one drug has measurable plasma levels, again increasing the probability of creating lifelong resistance. This problem is most notorious for Atripla (Gilead Sciences, Foster City, CA) (the combination oral tablet of efavirenz, tenofovir disoproxil, and emtricitabine) since the efavirenz component has a longer half-life (55 hr) compared with tenofovir (17 hr) or emtricitabine (10 hr). Thus, if Atripla is stopped, patients effectively receive efavirenz monotherapy for many days after the tenofovir and emtricitabine have been eliminated.
In practice, deciding what approach to take with antiretrovirals in the ICU is an individualized process for each patient, often in consultation with the infectious disease physician. Perhaps the biggest way a pharmacist can make an impact is to be alert for the possibility of unintentional monotherapy, especially in scenarios where not all of a patient’s antiretrovirals can be administered per tube, or providers are restarting antiretrovirals when GI absorption is uncertain.
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