By 2020, about 70% of people living with HIV will be over the age of 50, and as they age, they will inevitably be administered even more medications. Long-term survivors have taken a variety of different antiretrovirals for decades, to which have been added other drugs to control not only complications of HIV but also side effects of the medications themselves, including hypertension, diabetes, cognitive impairment, hypogonadism, bone density problems, and high cholesterol. Because normal aging typically results in a variety of other conditions, those who are aging and living with HIV find themselves taking more pills more often.
The administration of multiple medications is known as “polypharmacy,” although exact definitions vary considerably. Some authors describe polypharmacy as simply prescribing more medications than are clinically needed, although the most common definition is the concurrent use of at least five drugs.
In some ways, grappling with issues related to aging is a luxury that many of us living with HIV thought we would never experience. Medications saved our lives, but consistently taking a variety of pharmaceuticals for decades has resulted in serious complications, including heightened potential for drug-drug interactions and toxicity. Finding the proper balance between risk and benefit can sometimes be more art than science. Accurate prescribing information for persons living with HIV is limited because drug studies typically involve younger subjects, and studies for medications unrelated to HIV rarely involve potential interactions with persons on antiretroviral therapy.
There are several risk factors related to polypharmacy among aging adults living with HIV. The first is simply the result of taking multiple medications, thereby increasing the chance of adverse drug reactions and drug-drug interactions. Among persons living with HIV, additional medications that serve as markers for increased potential for interactions and adverse drug events include ritonavir (Norvir)- and cobicistat (Tybost)-boosted protease inhibitors and integrase strand-transferase inhibitors, statins, tenofovir disoproxil fumarate (Viread), H2-antagonists, and proton pump inhibitors.
Aging itself plays a significant role in several ways. Age-related physiologic changes affect pharmacokinetic (how the body affects the drugs) and pharmacodynamic (how the drug affects the body) properties of medications. These physiologic changes are impacted by a number of factors, including patient genetics, lifestyle, and environment. Highly active antiretroviral therapy, along with other medication, is cleared through hepatic metabolism and renal elimination. Aging can result in a decline in such liver and renal function, which can, in turn, impair how the body processes a medication. Such age-related concerns need to be considered, especially when hepatotoxic medications — such as the majority of protease inhibitors (PIs) and NNRTIs — are prescribed. Other medications typically taken by older persons living with HIV, such as anti-cholesterol drugs, increase the complexity of the situation and make the monitoring of liver function in older adults especially important.
Age alone, however, cannot explain the decreased capacity of organs to process medications. Comorbidities (two or more simultaneous conditions) actually play a more significant role, creating a situation unique to each individual in which chronological age may not always correlate to biological age. The increased prevalence of hypertension, increased cholesterol, and heightened blood sugar levels, among others, makes the close monitoring of all medications especially important for persons living with HIV.
Health care providers should perform a medication reconciliation annually, along with a review of current medications at each visit, and eliminate those that are no longer necessary. This significantly reduces potential drug interactions and toxicity. This process can be complicated by the fact that many prescribers are hesitant to discontinue or adjust medications that they did not initiate. It is recommended that patients physically bring their medications to the office so that any discrepancies in the medical record can be corrected and proper use of the drugs can be reviewed with patients.
There are resources for prescribers, such as Epocrates, Lexi-Comp, and Tarascon, which can help monitor potential drug interactions. Of special interest for antiretroviral drug interactions is the University of Liverpool’s online tool.
Additionally, validated screening instruments exist that can reduce the chances of prescribing medications that can cause harm to aging adults. The Beers Criteria focuses on potentially inappropriate medications for older patients, while STOPP (the screening tool for older person’s prescriptions) tends to focus on potentially inappropriate medication-disease combinations. A third screening tool, the Medication Appropriateness Index, utilizes a ten-item list to evaluate the appropriateness of a particular medication.
Providers should also remain aware of the pill burden experienced by people living with HIV. There is evidence that higher dose frequency and greater regimen complexity result in poorer medication adherence. Sometimes simple solutions, such as the use of a single pharmacy (ideally a specialty pharmacy to further reduce adverse events), medication delivered through dosed bubble-packs, pill boxes, centralized data bases of prescribed medications, and personalized patient counseling, are the most effective safeguards against potential drug-drug interactions, adherence concerns, and toxicity.
The phenomenon of an aging population living with HIV, with some having taken antiretrovirals for decades and being expected to continue doing so for the rest of their lives, represents a unique risk for complications due to polypharmacy. A model consisting of four interventions has been proposed to mitigate the risk. The components are:
- Complete Medication Reconciliation: This comprises an annual update of all medication changes and an assessment of adherence and related symptoms, including all supplements and over-the-counter medications.
- Assess for Substance Misuse: Substance misuse can not only result in complications for adherence but also impact the metabolism of medications and increase the risk for drug interactions. Many standard assessment tools can be briefly administered in any medical setting to evaluate risk.
- Assess and Rank Each Medication According to Risk and Benefits: This should include prioritizing antiretroviral therapy and any medications for substance-use disorders and utilizing risk indices to evaluate potential concerns.
- Prioritize and Plan With Patient: Goals for stopping treatments (if appropriate) should be evaluated, along with developing strategies to monitor medication-induced symptoms and adverse events, always incorporating patient preferences.
As the population living with HIV ages, there will be an inevitable increase in both the number of drugs administered and resulting complications. Awareness, monitoring, and ongoing collaboration between provider and patient are essential to preserve health to the greatest extent possible.
By David Fawcett