Navigating Polypharmacy and Drug–Drug Interactions in People with HIV

Among the major achievements in HIV care is the advent of effective antiretroviral therapy (ART) that has led to longer life expectancy. Since ART is lifelong, however, this comes with a new set of challenges, as older persons tend to have other chronic diseases that are managed with separate medications. Cardiovascular disease, which is more prevalent in people with HIV vs people without HIV, is one of the most common culprits. Liver diseases and cancers are also more common in older patients, and their treatments can pose issues from a drug–drug interaction perspective. We must therefore be mindful and vigilant about the effects of polypharmacy as our patients with HIV age.

Polypharmacy and ART
When initiating ART, it is important to obtain a thorough medical history to uncover any comorbid conditions and medications the patient may be taking, including over-the-counter medications and complementary alternative medications. In an ideal world, all of our health systems would communicate with one another, and we would capture the prescribing provider and pharmacies where patients are filling their prescriptions. However, we all know this is not necessarily the case, and therefore, it is important to fully investigate.

Moreover, I recommend establishing yourself as a central provider who performs a medication reconciliation at every visit. It is important to maintain an up-to-date list and ensure that patients are tolerating their medications. Patients with comorbid conditions may be seeing multiple providers in different specialties, and our patients with HIV tend to receive most of their primary care in their HIV clinic. So, if you are a central hub for that patient, make sure that you or a pharmacist reviews the list of medications routinely—at each visit—when patients present for care.

Evaluating Potential Drug–Drug Interactions
When assessing the risk for drug–drug interactions in people receiving ART, protease inhibitor and boosted integrase inhibitor regimens have the most potential for interactions. Indeed, anytime a pharmacokinetic enhancer is involved, the risk for drug–drug interactions increases. Nonnucleoside reverse transcriptase inhibitor–based regimens also pose a risk of drug–drug interactions. Though we are in the era of integrase strand transfer inhibitors (INSTIs), which have far fewer drug–drug interactions than other ART drug classes, there are still important potential interactions to consider. In particular, polyvalent cations—such as aluminum, calcium, iron, magnesium, and zinc—may chelate with INSTIs enterally and pose significant risks that are sometimes overlooked. Another important interaction to remember is between dolutegravir and metformin, wherein dolutegravir can increase metformin concentrations, leading to increased adverse effects.

When patients present with a new adverse event, it is important to consider the potential for drug–drug interactions. When this occurs, I perform a thorough history and determine if they have recently started a new medication. I also review their medication list to determine if the adverse event is commonly associated with a medication on their list and if it can be worsened by a drug–drug interaction. For example, if patients receiving a boosted protease inhibitor have recently started a calcium channel blocker, they might become hypotensive and experience lightheadedness. Of more importance, if someone is receiving a pharmacokinetic enhancer–based regimen and has been started on an anticoagulant or an antiplatelet that was not carefully chosen, they could be at an increased risk of bleeding.

Polypharmacy and Adherence
In my experience, more complex medication regimens can lead to challenges with adherence. It can be a burden on patients to remember to take multiple pills or to keep up with the frequency of dosing. Fortunately, we have great fixed-dose single-tablet regimens for treating HIV, but this may be just one of many medications older patients with HIV are receiving. 

As a pharmacist, whenever I can simplify patients’ medication regimens, I do. That could mean simplifying their HIV or non-HIV medication regimens, considering combination pills, or consolidating dosing frequency. I also like to consider how their medication regimens will fit into their lifestyle. For example, if a patient works night shifts, evening dosing may be better. 

Resources
For healthcare professionals navigating polypharmacy challenges among people living with HIV, I recommend the University of Liverpool HIV Drug Interactions resource. This program allows you to enter an antiretroviral medication and the comedication and check for potential drug–drug interactions. I especially like how it provides available literature detailing the consequences of co-administration. In addition to a color-coded indicator specifying the potential for interactions, you can see a summary of the clinical studies that have informed the warning. I think this resource is useful for both HIV specialists and non-HIV specialists.

The Micromedex Drug Interactions Tool is another great resource. I also recommend checking the Department of Health and Human Services HIV guidelines, which contain thorough drug–drug interaction tables broken down by ART class. Finally, the CDC has helpful online references, especially for common concomitant medications, such as antituberculosis treatments.

Summary
As people with HIV achieve longer life spans thanks to improved ART regimens, healthcare professionals must be mindful about accommodating treatment for common chronic diseases that arise. Although some may think that drug–drug interactions are a relic of the protease inhibitor era of HIV treatment, significant adverse events can occur from drug–drug interactions with newer agents. Only through thorough and consistent follow-up and consideration of concomitant medications can we minimize adverse events and preserve the efficacy of all our patients’ medications.

Your Thoughts?
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