Living and Aging With HIV: Recognition and Management of Common Prescribing Pitfalls

With advancements in antiretroviral therapy (ART), people with HIV (PWH) are now living longer and developing age-related chronic conditions that require medications in addition to ART. Studies have demonstrated that older PWH have a substantially higher frequency of medication- related problems, polypharmacy, and potential drug-drug interactions (DDIs) compared not only with their younger counterparts but age-matched HIV-negative counterparts.^1-3 To better serve our growing population of older PWH, we must assess prescribing patterns as they pertain to HIV and aging.

The Swiss HIV Cohort Study (SHCS) is a multicenter prospective cohort study that has been enrolling PWH in Switzerland since 1988. As a collaboration among the infectious disease outpatient clinics of all Swiss University Hospitals, 2 large regional hospitals, and affiliated smaller hospitals, the SHCS represents one of the largest cohorts of PWH followed in any country and one of the only ones prospectively analyzing prescriptions filled by PWH.4 Previously, the SHCS has found a higher number of comedications and more severe effects of DDIs in older PWH compared with their younger PWH counterparts.^3,5

To better understand the prevalence of potentially inappropriate medications (PIMs), this study’s authors compared prescribed medications, polypharmacy, and potential DDIs between young and older PWH in 2 SHCS outpatient sites.⁶ Participants were contacted by mail 1 week prior to their twice-yearly SHCS appointment and asked to report all current medication names and doses. Those 65 years and older were classified as “older.” Drugs reported by participants included ARTs, prescription medications, and over-the-counter medications. If a drug contained 2 or more active agents, each substance was counted individually. Polypharmacy was defined as concurrent administration of 5 of more comedications in addition to ART. PIMs were assessed using the classical Beers Criteria, and anticholinergic burden was measured by the Anticholinergic Risk Scale.^7,8

Because of data gleaned from prior SHCS research, this study focused on cardiovascular (CV) and central nervous system (CNS) medications; these 2 therapeutic classes were the most used by PWH and had the most clinically relevant potential DDIs with ARTs. All the returned forms indicating use of at least 1 CV or CNS comedication were included in the study, and potential DDIs were screened and flagged based on their clinical significance. All medication forms provided during the observed 24-month period were considered in the analysis.

Of the 996 PWH participating in the study, 874 (88%) were aged less than 65 years, with a median age of 49 years; the remaining 122 (12%) were 65 years and older, with a median age of 71 years. A total of 1610 forms were collected, with the majority of participants (57%) completing the form on 2 separate occasions. Older PWH were more likely to be prescribed a combined ART regimen in addition to their nucleoside reverse transcriptase inhibitor (NRTI) backbone. Combined ARTs were defined as boosted protease inhibitor (PI) plus integrase strand transfer inhibitor (INSTI), a boosted PI plus nonnucleoside reverse transcriptase inhibitor (NNRTI), or a boosted PI plus INSTI plus NNRTI. These regimens represented complex ARTs that were characterized by a higher potential to cause DDIs. Nearly 50% of all ART regimens included an INSTI, regardless of age group (Table). The number of comedications increased with age, with older PWH using a median of 4 comedications compared with a median of 1 in their younger counterparts. CV medications were more commonly prescribed to older PWH, whereas CNS medications were more commonly prescribed to younger PWH. A total of 38 older patients (31%) had been prescribed at least 1 PIM, the majority of which were benzodiazepines and hypnotics.

Over the study period, 767 forms collected from 500 PWH contained at least 1 CV or CNS medication; the majority of forms (54%) did not contain any potential DDIs. Of those that did, there was no significant difference in potential DDI severity between PWH age groups. Similar to prescribing distribution, older PWH were more likely to have potential DDIs between ART and CV drugs, whereas younger PWH were more likely to have potential DDIs between ART and CNS drugs. Ritonavir-boosted darunavir, a boosted PI, was the most common ART involved in potential DDIs of higher severity. Of the potential DDIs between ARTs and CV or CNS medications nearly all were managed properly through dosage adjustments.

These new data from the SHCS demonstrate that not only are older PWH prescribed a higher number of comedications, but they also receive more complex ART regimens. Interestingly, there was not a significantly higher frequency of potential DDIs in older PWH compared with younger patients; this could be explained by an overall low rate of potential DDIs and robust prescriber knowledge of these interactions. However, it is also important to note that this analysis focused on only 2 therapeutic classes, and potential DDIs were assessed between only 2 compounds; this does not full address the complexity of DDIs noted in polymedicated patients. In addition to receiving potential DDIs, 31% of older PWH were prescribed at least 1 PIM during the observed period. This is likely an underestimate, as the study could not include all criteria that define inappropriate prescribing.

This study’s results reinforce that potential DDIs and polypharmacy remain a common problem for older PWH. As the realms of HIV medicine and geriatric medicine continue to overlap, we must recognize and address these prescribing issues using well-established geriatric principles and approaches.

Hazra is an assistant professor in the Section of Infectious Diseases and Global Health at the University of Chicago in Illinois. His research and clinical interests center on sexually transmitted infections and their impact on sexual and gender minorities of Chicago’s South and West sides.

References:

1. Greene M, Steinman MA, McNicholl IR, Valcour V. Polypharmacy, drug-drug interactions, and potentially inappropriate medications in older adults with human immunodeficiency virus infection. J Am Geriatr Soc. 2014;62(3):447-453. doi: 10.1111/jgs.12695.
2. Edelman EJ, Gordon KS, Glover J, McNicholl IR, Fiellin DA, Justice AC. The next therapeutic challenge in HIV: polypharmacy. Drugs Aging. 2013;30(8):613-628. doi: 10.1007/s40266-013-0093-9.
3. Marzolini C, Back D, Weber R, et al; Swiss HIV Cohort Study Members. Ageing with HIV: medication use and risk for potential drug-drug interactions. J Antimicrob Chemother. 2011;66(9):2107-2111. doi: 10.1093/jac/dkr248.
4. Home page. Swiss HIV Cohort Study & Swiss Mother and Child HIV Cohort Study website. shcs.ch/. Accessed February 12, 2020.
5. Marzolini C, Elzi L, Gibbons S, et al; Swiss HIV Cohort Study. Prevalence of comedications and effect of potential drug-drug interactions in the Swiss HIV Cohort Study. Antivir Ther. 2010;15(3):413-423. doi: 10.3851/IMP1540.
6. Courlet P, Livio F, Guidi M, et al; Swiss HIV Cohort Study. Polypharmacy, drug—drug interactions, and inappropriate drugs: new challenges in the aging population with HIV. Open Forum Infect Dis. 2019;6(12):ofz531. doi: 10.1093/ofid/ofz531.
7. American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767.
8. Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168(5):508-513. doi: 10.1001/archinternmed.2007.106.