Polypharmacy in People with HIV: A Growing Problem

Today, about a third of all people living with HIV are 50 and older, thanks to  combination antiretroviral therapy (ART) that has transformed the infection from a death sentence into a chronic, manageable condition. By 2030, experts predict, half of all HIV-infected individuals will be 50 or older.¹

With age, however, comes a host of chronic diseases and medical conditions such as diabetes, hyperlipidemia, hypertension, depression, anxiety, and heart disease that often require multiple medications to manage. Combined with several ART drugs, this polypharmacy can increase the risk of adverse drug reactions, falls, cognitive impairment, urinary incontinence, and nonadherence due to increased pill burden. In people with HIV, it may also affect the efficacy of ART and, together with nonadherence, lead to higher viral loads and drug resistance.

A study recently published in the Journal of General Internal Medicinesought to quantify the prevalence of clinically-relevant polypharmacy in the 50-plus population using data from the HIV Outpatient Study (HOPS), an ongoing observational study of HIV-infected adults that began in 1993. Researchers from Temple University in Philadelphia found that HIV-infected individuals older than 50 were prescribed a median of five or more non-ART medications, compared to two for those younger than 40, three for those ages 40 to 49, and four for those age 50.

Of the 3,810 patient records the researchers analyzed for 2006 to 2010, 7% (267) of patients were prescribed at least one contraindicated ART/non-ART combination, and a third (1,267) were prescribed at least one drug combination with moderate or high evidence of interactions.

The most common contraindicated combinations were:

•    Proton pump inhibitor (PPI) with atazanavir or nelfinavir
•    Protease inhibitor (PI) with simvastatin or lovastatin
•    Protease inhibitor with contraindicated benzodiazepines

The most common combinations with evidence of interaction were:

•    H2-receptor antagonists and/or PPIs with PIs
•    Erectile dysfunction agents with PIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs)
•    Antidepressants (bupropion, sertraline, and paroxetine) with PIs and NNRTIs
•    Lithium with atazanavir

Variables associated with contraindicated prescriptions included older age, anxiety dyslipidemia, higher daily non-ART medication burden, and taking a PI.

A 2011 review found that patient risk factors for clinically significant drug interactions with ART included being 43 or older, having more than three comorbidities, and being treated with three or more ARTs or with a PI.

While it wasn’t unexpected that 33% of patients were taking potentially interactive drugs, said lead author Carol Holtzman, PharmD, she and her colleagues were surprised by the number of patients taking contraindicated combinations. “You shouldn’t do it, you shouldn’t have it, but sometimes it happens,” added Holtzman, who is clinical assistant professor at the Temple University School of Pharmacy. “It could be that the doctor is aware of it and decided to monitor the patients more closely. Patients really do need certain medications and it might be unavoidable.”

However, the problem may also arise due to lack of knowledge, particularly given the growing arsenal of ART drugs. Other reasons include the absence of alternative medications, or that the healthcare provider is not aware that the patient is taking other medications. Many HIV-positive patients are treated by more than one physician, she said.

Indeed, another 2011 study  found that non-HIV providers prescribed nearly a quarter of drugs related to clinically significant drug interactions. That study, conducted in a Veteran’s Administration HIV clinic, also found that at least half of patients, regardless of age, had clinically significant drug interactions related to both ART and non-ART medications. The most common non-ART classes related to clinically significant drug interactions were psychotropic, anti-infective, acid suppressors, antihypertensives, antihyperlipidemics, and erectile dysfunction agents. Protease inhibitors were the most frequent ART class associated with drug interactions.

Even when physicians use computerized order entry (COE) systems designed to warn them of potential interactions, said Holtzman, many just override the alerts, a trend called “alert fatigue.” It’s not always their fault, Holztman said, since COE databases are often out of date.

Holztman expects that as the number of people 50 and older living with HIV continues to increase, the percentage of clinically significant drug interactions will also rise.

The message for physicians, she said, is to evaluate a patient’s entire medication list  carefully and also to ask patients what they are taking. For instance, many acid-reducing medications are available over-the-counter, so patients may not include them on medication lists.

 Another alternative is to involve pharmacists in reconciling medications. Singlehandedly managing the complex polypharmacy of HIV-infected may not be realistic, said Holtzman.  “Physicians don’t have that kind of time.”

For a complete list of drug-drug interactions, dosing, and recommendations, see the Health and Human Services Guidelines for the Use of Antiretroviral Agents in HIV-1-infected Adults and Adolescents.

References:

REFERENCE1. Brooks JT, Buchacz K, Gebo KA,

et al.

HIV infection and older Americans: the public health perspective.

Am J Public Health

2012;102(8):1516-1526.