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Drug Deescalation
Less Is More: Managing Polypharmacy for People Living With HIV and Multimorbidity

Released: August 13, 2025

Alexis E. Horace
Alexis E. Horace, PharmD, BCACP
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Key Takeaways
  • Managing polypharmacy can seem overwhelming, but the key is to address each condition and each medication one by one.
  • Even when all the drugs in a patient’s regimen are evidence-based and necessary, there may be ways to help with adherence outside of drug de-escalation.

One of my biggest challenges as a pharmacist who provides HIV care is helping older adults manage polypharmacy, especially when they have multiple chronic conditions. Polypharmacy­—the concurrent use of 5 or more medications—is associated with decreased adherence, increased pill fatigue, more adverse drug reactions, drug–drug and drug–disease interactions, and even higher mortality. Thus, creating drug de-escalation or simplification plans that honor each patient's goals is a critical aspect of my practice. 

Drug De-escalation for a Person Living With Virologically Suppressed HIV and Multimorbidity
One of the best examples of an intervention I recently made involved a patient I’ll call JK. He had multiple comorbidities, including HIV, and was taking 25 different medications. When he arrived for his medication therapy management appointment, he appeared overwhelmed by his drug regimen and unmotivated to engage in care. His history included diabetes, hypertension, gastroesophageal reflux disease, mental health concerns, a prior Cryptococcus meningitis infection, HIV, chronic kidney disease, thyroid disorder, and benign prostate hyperplasia. He brought in multiple unopened medication bottles, a sign of nonadherence and medication overload.

Even as a pharmacist familiar with complex medication regimens, I myself sometimes feel overwhelmed when reviewing cases like this—and that’s normal! The key is breaking it down into manageable steps. My first step with JK was explaining the purpose of the visit and then taking time to understand his personal health goals. This helped me create a shared decision-making environment and learn which changes would be most meaningful to him.

JK told me he wanted to reduce the number of medications he was taking because he didn’t understand what each was for. He also had concerns about side effects and wanted a better system to stay on track with his treatment.

I reviewed each of his conditions to make sure they were being treated appropriately, using evidence-based guidelines. I then asked JK what he found overwhelming about each regimen. These conversations are often the best opportunities for education on why certain medications are important, or when we can safely remove or adjust therapies that are no longer beneficial or welcomed by the patient.

For example, JK was taking dolutegravir and emtricitabine plus tenofovir disoproxil fumarate for HIV, along with fluconazole as maintenance therapy for a past Cryptococcus infection. He had recently completed 14 months of fluconazole, and his labs showed declining kidney function. His viral load was undetectable, and his CD4 count was in the 600 cells/mm3 range. With this in mind, I recommended switching him to a once-daily tablet that includes bictegravir, emtricitabine, and tenofovir alafenamide, which is safer for patients with lower kidney function. I also recommended discontinuing fluconazole, as he had completed adequate treatment, had no signs of active infection, and his recent Cryptococcus titers were negative.

Barriers to Managing Polypharmacy
With just those changes, we reduced his medication list from 25 to 23. I could see that he was starting to feel more engaged as we moved through his list, and together, we tackled a few more opportunities for streamlining.

However, there are definitely barriers to managing polypharmacy in people living with HIV. Many chronic conditions require multiple medications, and patients can quickly end up with 16 or more prescriptions if they’re managing just 4 conditions. Often, these therapies are evidence-based and necessary, preventing de-escalation altogether.

Another challenge is that patients with complex medical histories usually see several specialists who prescribe medications independently of each other. In a system that is already stretched thin, it takes time and coordination to communicate with other healthcare professionals, confirm medication lists, and implement changes. It's also hard to assess adherence when patients use multiple pharmacies. On the patient side, coming to multiple appointments just isn’t feasible for some. Simplifying a regimen takes time, and not every patient has the capacity or support to go through a lengthy process.

Despite these challenges, I genuinely enjoy helping patients with HIV navigate complex medication regimens. I find it incredibly rewarding to make their treatment plans more manageable, helping them get closer to their healthcare goals. It takes time and teamwork, but the results are worth it.

I’m happy to share that by the end of our work together, JK’s medication list was reduced from 25 to 18. We also created a medication strategy that included having his pharmacy provide blister packs to support his adherence. JK told me he hadn’t realized how valuable it could be to work with a pharmacist and admitted he was skeptical about the appointment at first. By the end, he said he was glad he came and I’m grateful I had the opportunity to help him.

Your Thoughts
What are your biggest challenges with managing polypharmacy for people living with HIV? What strategies do you use to overcome these barriers? Leave a comment to join the discussion!

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