Drew Halbur, BSPharm, BCACP, AAHIVP

Nationally, over 1.2 million Americans are living with HIV, of which 13% are unaware of their infection.

 The management of HIV infection has drastically changed over the last 10 years with the development and enhancement of more than 14 antiretroviral medications, including better formulations and various combination pills approved by the Food and Drug Administration.

 Since entering the decade of enhanced formulations of antiretrovirals and the initiation of pre-exposure prophylaxis in 2014, there has been both a significant reduction in HIV-related illnesses and an increase in proportion of patients with viral suppression—with a more than 19% decline in new HIV diagnoses over the last decade.

Other significant factors that have contributed to this positive impact include early initiation of antiretroviral therapy (ART) and the use of this therapy for reducing the risk of HIV transmission. Both the START and TEMPRANO studies were landmark randomized controlled trials published in 2015 that provide the highest level of evidence to support the use of early initiation of ART, regardless of CD4 cell count, for benefit in boosting immune recovery and preventing clinical events.

 The treatment-as-prevention model is a method studied in the HIV Prevention Trials Network (HPTN 052) study that demonstrated a reduction of sexual transmission of HIV among heterosexual couples, with full viral suppression from ART.

The Department of Health and Human Services (DHHS) recommends triple combination therapy for treating HIV, with dual nucleoside reverse transcriptase inhibitors and either an integrase strand transfer inhibitor or protease inhibitor in combination with a pharmacokinetic enhancer agent (ie, ritonavir or cobicistat) for HIV treatment-naïve patients.

 These regimens are often complex and have clinically significant drug-drug interactions; without appropriate monitoring, there is a high risk for medication errors and unwanted adverse effects, especially in those with multiple comorbidities. The incidence of medication errors related to antiretroviral agents in hospitalized patients has ranged between 21% and 72%.

 Errors were observed in all major antiretroviral drug classes and include medication omission, inappropriate scheduling of drug administration, drug interactions, and incorrect dosing.

Pharmacists play vital roles in optimizing HIV treatment outcomes in multiple ways and in all medical settings, such as ensuring patients are taking a complete and appropriate regimen, recommending alternative therapy, dose or formulation adjustments, mitigating drug-drug interactions, and modifying drug schedules to optimize absorption. In order to improve the quality of care in HIV-infected patients, more institutions are partaking in several forms of ART stewardship, often composed of a team led by pharmacists specialized in infectious diseases and/or HIV.

Pharmacist-Led Antiretroviral Stewardships 

The development and implementation of pharmacist-led antiretroviral stewardships have been seen in numerous published studies across the country.

 Current literature reports a profound impact on improving safety in HIV patients through pharmacist interventions via medication error prevention and daily monitoring. Retrospective studies have seen rates of antiretroviral stewardship interventions for medication errors related to antiretrovirals increase from 16% to 52%. Various methods of stewardship interventions have been utilized, including prescriber and pharmacist education,

The impact of these methods is discussed below:

can assist prescribers in appropriate selection and dosing of antiretrovirals. Zucker and colleagues’ study saw modest reduction in medication errors (from 45% to 36%) with provider education and order sets in an urban medical center setting.

can also facilitate correct prescribing of antiretrovirals and preventing potential drug-drug interactions or improper timing of administration. Another study performed by Guo and colleagues saw error rates reduced by 35% overall, primarily in incorrect doses and drug interactions by over 40%.

seem to show a significant reduction in these studies. In the previously mentioned Zucker study, prospective audit reduced errors to 12%.

 Other studies saw rates of pharmacist interventions on drug interactions increase from 43% to 95%11 and medication error rates decrease from 50% to 34%.

Given these results, pharmacists with specialized training and knowledge in HIV are in a unique position to lead stewardship initiatives to significantly reduce medication errors related to ART in numerous ways. In the hospital, there are many opportunities for pharmacist intervention and improving patient safety, including identifying drug-drug interactions. Common inpatient medications such as proton pump inhibitors and statins may have clinically significant and unfavorable consequences. In addition, pharmacists can verify appropriate and complete ART regimens, the accurate route of administration, adjustments for renal and hepatic function, and indications for opportunistic infections associated with HIV/AIDS. Similarly, these interventions can be replicated in the outpatient setting, however, reported data are limited.

Challenges of Pharmacist-Led Antiretroviral Stewardships 

Pharmacists, as part of antiretroviral stewardship teams, may face such barriers around therapeutic interchange of newer formulations, such as Genvoya and Descovy, with formulary antiretrovirals or interchange between routes of administration for formulations without alternatives. At times, barriers may lead to a temporary hold on medication administration, which may cause concern for virologic failure. In HIV-treated patients with hepatitis B co-infection, abrupt discontinuation of ART can also lead to an acute flare of hepatitis B. Consequently, in antiretroviral-experienced patients with viral resistance, treatment regimens may become more complex, requiring use of older antiretroviral agents, which have greater potential for drug-drug interactions and toxicity. At this time, further guidance is needed to determine the appropriate process of therapeutic interchange within hospital formularies.

Beyond poor engagement in HIV treatment, providers and HIV-infected individuals may face obstacles when disruption occurs along the HIV care continuum, also known as the Cascade of Care.

This model—defined in 2011 by Edward M. Gardner, MD, and colleagues&mdash;outlines five sequential steps of HIV medical intervention including: diagnosis, linkage to care, retention in care, acquisition of ART, and achievement of viral suppression.

 Frequently, HIV-infected patients who face psychosocial or economic barriers are at risk of lost to care. Pharmacists, as part of antiretroviral stewardships, can assist with strengthening the continuum of HIV care by ensuring linkage to care after hospital discharge or outpatient.

The Cascade of Care has become such a significant model that former President Barack Obama prioritized efforts in addressing this model through executive order of the HIV Care Continuum Initiative in 2013.

 This step-in implementation of the national HIV/AIDS strategy focuses efforts on increasing the proportion of patients in each stage of the continuum by increasing access to HIV testing, care, and treatment.

Within institutional care of HIV-infected patients, one major stage of the Cascade of Care that is affected is initiation of ART during hospitalization, particularly in those with late entry into medical care when concomitantly diagnosed with HIV/AIDS and opportunistic infection or active seroconversion. Pharmacists involved with the care of these individuals play an important role as patient advocates by facilitating appropriate and timely initiation of ART where added benefit has been previously seen.

Additionally, appropriate transition into outpatient care is a key intervention to ensure patients are linked with and engaged in care with health care providers, including pharmacists with special training in HIV ART. This ultimately leads to viral suppression and optimized HIV treatment outcomes.

There is still much left to be done even with the great progress that has been made over the recent years with the reduction in HIV diagnoses and improved viral suppression. The medication error rate in ART regimens reported in hospitalized patients is alarming, but it is also a great opportunity for pharmacists to optimize and improve the medication use process, as the results of published studies have already demonstrated. Further direction with impact of ART stewardship in the ambulatory setting and with guidance on appropriate therapeutic interchange within hospital formularies are needed. With a variety of methods to reduce medication errors, such as use of computerized order entry sets, provider education, and prospective feedback, pharmacists can continue to work to make an impact in advancing HIV patient care and supporting the continuum of care.

Acknowledgements: The authors would like to acknowledge the contribution and guidance of Milena McLaughlin, PharmD, MSc, BCPS-AQ ID, AAHIVP.

Feature Image Source: ScienceSource/Francis Sheehan 

Drew Halbur, BSPharm, AAHIVP, BCACP, is a clinical pharmacist at a Walgreens local specialty pharmacy as a part of the Howard Brown Health Center, the largest LGBTQ health organization in the Midwest. He completed his pharmacy degree at Drake University in Des Moines, IA, and has worked in HIV primary care for almost 20 years.  

Betty Vu, PharmD, is a PGY2 infectious disease pharmacy resident at the Department of Pharmacy at Midwestern University, Chicago College of Pharmacy. She completed her PGY1 pharmacy residency at Montefiore Medical Center in Bronx, NY, and her Doctor of Pharmacy degree at the University at Buffalo. She is an active member of ACCP, IDSA, and SIDP.

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Pharmacists play vital roles in optimizing HIV treatment outcomes in multiple ways and in all medical settings.

Drew Halbur, BSPharm, BCACP, AAHIVP

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