Antiretroviral Stewardship: The Time is Now
In this narrative review of studies evaluating antiretroviral stewardship programs (ARVSPs), we propose core elements for ARVSPs that are based on published evidence, clinical experience, and adapted from antimicrobial stewardship programs.
Accrediting health care organizations have established specific requirements for antimicrobial stewardship programs (ASPs) in hospitals.1,2 While these programs focus on appropriate antibacterial and antifungal use and outcomes, antiretroviral therapy (ART) management and monitoring are not included in their requirements. Although standardized guidance has not been established for the management of ART in hospitals, there is an increased call to action for the establishment of antiretroviral stewardship programs (ARVSPs). Recently, the Infectious Diseases Society of America, the HIV Medicine Association, and the American Academy of HIV Medicine published a joint recommendation for antiretroviral stewardship implementation in inpatient practices.3
A patient who adheres to an optimized ART regimen can restore and maintain immunologic function, decrease their risk of morbidity and mortality, and prevent HIV transmission. Interruptions in ART adherence and incomplete or incorrect regimens can lead to resistance and virologic failure, which has the potential of limiting future ART options and increasing pill burden. ART is complex: There are an increasing number of agents and combination products available; many providers are unfamiliar with ART; and the ART formularies at different inpatient institutions vary, which can contribute to increased medication errors in this population.
The medication error rates in people living with HIV (PLWH) range from 5% to 86%, as reported in various studies.4 Medication errors can occur at any point in hospitalizations and transitions of care; however, most errors occur at hospital admission, and many of those errors are left uncorrected at discharge. The most common ART medication errors include ART omission and incorrect regimen prescribing, incorrect dosing, and drug interactions.5
Various studies have reported the benefits after implementing ARVSPs for adult hospitalized PLWH.6-14 This article is not intended to be a comprehensive or systematic review of all ARVSP programs. Instead, we aim to highlight key elements of successful programs to serve as examples for hospitals that are seeking to start, modify, and/or evaluate their ARVSP, or to incorporate ART review into their ASP. The most common analysis utilized in the published studies we reviewed was a quasiexperimental retrospective comparison of patients before and after novel ARVSP intervention(s). All programs we reviewed included a prospective audit and feedback (PAF) component. This was either standard-of-care at baseline (preintervention) and continued or implemented as a new program element. Clinical specialists or staff pharmacists performed PAF, with oversight from a specialist.14 Some programs, such as those described by Zucker et al, DePuy et al, and Nimarko et al, used a team approach.9,12,13 Each ARVSP also included at least 1 additional element. This included health care provider education, electronic medical record (EMR) modifications, restricted ART ordering, and/or tools for staff pharmacists, such as a stewardship checklist or an HIV “pocket” guide. EMR modifications included alterations to default doses and frequencies, customized order-entry sets, and links to drug information resources.
The majority of studies we reviewed evaluated medication errors as their primary outcome.6,7,9-14 Each of these studies found a significant reduction in number of patients, admissions, or ART regimens with ART errors and/or an improvement in error detection post ARVSP implementation. Logistic regression analyses conducted by Sanders et al and Guo et al established independent associations between ARVSPs and reduced ART errors.6,7 Additionally, studies that compared error resolution before and after ARVSP implementation showed a significant improvement in the postimplementation phase.6.7,9-11,13-14 The study by DePuy et al did not have a comparator arm but found that 43% of admissions required at least 1 intervention during the study period, with an acceptance rate of 96% and an associated monthly cost savings of $21,952.12 A study by Billedo et al evaluated clinically significant drug—drug interactions (CSDDIs) as the primary outcome.8 This study similarly found significantly fewer CSDDIs at admission and during hospitalization in the postimplementation phase. All studies we reviewed on hospital ARVSPs in adults concluded that their interventions were beneficial.
Interestingly, we identified only 1 study that was conducted at a nonteaching community hospital.14 Results of this study were comparable with those at larger academic hospitals. While this represents an area for further research, it shows promise that ARVSPs are not only possible to implement but also beneficial across different hospital settings.
Although there is limited guidance on standards for implementing ARVSPs, our proposed core elements for these programs are based on clinical experience and published evidence, and they are adapted from ASPs.2
Establishing commitment from leadership is essential in procuring needed resources, including funding, dedicated full-time equivalents, appropriate technology, and approval of policies and procedures.
A leader or co-leaders, generally a pharmacist and/or physician, is identified and accountable for program outcomes.2
HIV pharmacotherapy expertise is critical for ARVSPs due to the complexities of ART, numerous CSDDIs, and typically high rates of medication errors in this population. Expertise in HIV can be established through formal training and/or advanced certifications, supplemented by continuing education. Depending on need, resources, and expertise, the ARVSP may be led by the same individual or group as the ASP.
Support from key members, including clinicians, department heads, information technology (IT) staff, and the pharmacy department, is crucial. IT staff are essential for streamlining processes, including the development of alerts notifying ARVSPs when ART is initiated, when CSDDIs exist, and when renal dosing is required. They can also assist in developing standardized ARVSP note templates as well as in collecting and reporting outcome data.
Most ARVSP interventions have focused on decreasing ART-related medication errors and CSDDIs15; however, a baseline assessment of institutional needs should be performed to identify specific priority areas. Some of the most effective foundational interventions for ASPs, such as PAF or preauthorization, could be considered equally effective for ARVSPs in the inpatient setting.2 In addition, formulary management, generation of reports via diagnosis codes to identify hospitalized PLWH, use of clinical decision support to alert the ARVSP of an ART order, and development of institution-specific postexposure prophylaxis guidelines may also be effective for inpatient programs.15 Alternately, outpatient ARVSPs may be best suited to establish standards for starting, modifying, and/or discontinuing pre-exposure prophylaxis (PrEP), ART, or opportunistic infection prophylaxis, as well as for identifying ways to overcome barriers to adherence to prescribed ART/PrEP. In particular, when ART is initiated during hospitalization, outpatient ARVSPs can facilitate access to prescribed ART and linkage to care, by providing resources to address socioeconomic limitations before discharge occurs. Once in the outpatient setting, ARVSPs can assess and ensure adherence to ART and retention in care. Medication reconciliation/ART review during transitions of care, prescriber education, pharmacy-based interventions (eg, dose adjustments, dose optimization, detection of CSDDIs and adverse events), and patient counseling are applicable to all settings and will help promote improved ART prescribing and outcomes for PLWH.
ARVSPs should develop a standardized process for tracking ART-related medication errors, which should include identifying the type (eg, CSDDIs, dosing errors, administration errors), timing (eg, admission, discharge) and source of error (eg, prescribing, administration, dispensing). Standardized documentation of the aforementioned components of ART-related medication errors and associated interventions, if applicable, will ensure a data-driven ARVSP. Additional measurements of interest may include demographic data, percentage of PLWH not on ART, rate of ART modification, and, if applicable, pre- and postintervention outcomes. Continuous tracking is critical to identify areas of emphasis and to develop interventions to improve ART prescribing.
Although less data-driven compared with ASPs, ARVSP reporting metrics will be somewhat dependent on location, either inpatient or outpatient. Reports should include, at a minimum, rate and type of ART errors, but may also include key issues discovered during data analysis. In both settings, regular updates to providers, pharmacists, nursing, and leadership will be necessary to document the successes and challenges of the ARVSP.
Although education is a common tool for ASPs, the most effective educational method remains unknown.16 A multifaceted approach that includes didactic lectures/in-services, pamphlets and/or posters, and EMR-based alerts will likely yield greater benefit than any single component. Use of formulary restriction with preauthorization and PAF, core strategies of many ASPs, may also promote case-based educational opportunities.2
ART review significantly reduces medication errors, prevents development of resistance, and improves outcomes in hospitalized PLWH. Institutions should incorporate the aforementioned core elements into already established ASPs or develop a dedicated ARVSP to address the challenges associated with inpatient ART.
Pérez is a clinical pharmacy specialist at University of Chicago Medicine. She also serves on the American College of Clinical Pharmacy HIV Practice and Research Network executive board and maintains AAHIVP credentialing through the American Academy of HIV Medicine.
Michienzi is a clinical assistant professor at the University of Illinois at Chicago College of Pharmacy. She provides specialty and primary care for patients living with, or at risk of, HIV, HCV, and other infectious diseases at university- and community-based ambulatory clinics and a prison telemedicine clinic.
Amber Ladak is the HIV clinical pharmacist in the Department of Infectious Disease of Augusta University in Augusta, Georgia. She also serves as a member of the Antimicrobial Stewardship Subcommittee of the Augusta University Medical Center Pharmacy and Therapeutics Committee, a member of the Quality Improvement Committee of the Augusta University Ryan White Program, as a preceptor for University of Georgia pharmacy students, and as a subinvestigator for numerous antiretroviral-related clinical trials.
Chastain is a clinical assistant professor at the University of Georgia College of Pharmacy, on the Southwest Georgia Clinical Campus in Albany. He is also the infectious diseases pharmacist and co-chair for the antimicrobial stewardship program for Phoebe Putney Memorial Hospital in Albany, Georgia.
- The Joint Commission. Approved: new antimicrobial stewardship standard. Joint Commission Perspectives. 2016;36(7):1-8. Accessed May 19, 2019. https://www.jointcommission.org/assets/1/6/New_Antimicrobial_Stewardship_Standard.pdf
- Core elements of hospital antibiotic stewardship programs. CDC. Updated 2019. Accessed June 2, 2020. https://www.cdc.gov/antibiotic-use/core-elements/hospital.html
- Koren DE, Scarci KK, Farmer EK, et al. A call to action: the role of antiretroviral stewardship in inpatient practice, a joint policy paper of the Infectious Diseases Society of America, HIV Medicine Association, and American Academy of HIV Medicine. Clin Infect Dis. 2020;70(11):2241-2246. doi: 10.1093/cid/ciz792
- Durham SH, Badowski ME, Liedtke MD, et al. Acute care management of the HIV-infected patient: a report from the HIV Practice and Research Network of the American College of Clinical Pharmacy. Pharmacotherapy. 2017;37(5):611-629. doi: 10.1002/phar.1921
- Li EH, Foisy MM. Antiretroviral and medication errors in hospitalized HIV-positive patients. Ann Pharmacother 2014;48(8):998-1010. doi:10.1177/1060028014534195
- Sanders J, Pallotta A, Bauer S, et al. Antimicrobial stewardship program to reduce antiretroviral medication errors in hospitalized patients with human immunodeficiency virus infection. Infect Control Hosp Epidemiol. 2014;35(3):272-277. doi:10.1086/675287
- Guo Y, Chung P, Weiss C, et al. Customized order-entry sets can prevent antiretroviral prescribing errors: a novel opportunity for antimicrobial stewardship. P T. 2015;40(5):353-360.
- Billedo JAS, Berkowitz LB, Cha A. Evaluating the impact of a pharmacist-led antiretroviral stewardship program on reducing drug interactions in HIV-infected patients. J Int Assoc Provid AIDS Care. 2016;15(1):84-88. doi:10.1177/2325957415600700
- Zucker J, Mittal J, Jen SP, et al. Impact of stewardship interventions on antiretroviral medication errors in an urban medical center: a 3-year, multiphase study. Pharmacotherapy. 2016;36(3):245-251. doi:10.1002/phar.1716
- Shea KM, Hobbs ALv, Shumake JD, et al. Impact of an antiretroviral stewardship strategy on medication error rates. Am J Health Syst Pharm. 2018;75(12):876-885. doi:10.2146/ajhp170420
- Pettit NN, Han Z, Choksi A, et al. Reducing medication errors involving antiretroviral therapy with targeted electronic medical record modifications. AIDS Care. 2019;31(7):893-896. doi:10.1080/09540121.2019.1566512
- DePuy AM, Samuel R, Mohrien KM, et al. Impact of an antiretroviral stewardship team on the care of patients with human immunodeficiency virus infection admitted to an academic medical center. Open Forum Infect Dis. 2019;6(7):ofz290. doi:10.1093/ofid/ofz290
- Nimarko K, Bandali A, Bias TE, Mindel S. Impact of an antimicrobial stewardship team on reducing antiretroviral medication errors. Ann Pharmacother. 2020;1060028019900677. doi:10.1177/1060028019900677
- Bunn HT, Hester EK, Maldonado RA, Childress D. Evaluation of human immunodeficiency virus medication errors in a community hospital following the implementation of a pharmacist‐led antiretroviral stewardship program. JACCP. 2020;3(3):593-600. doi:10.1002/jac5.1196
- Michienzi SM, Ladak AF, Pérez SE, Chastain DB. Antiretroviral stewardship: a review of published outcomes with recommendations for program implementation. J Int Assoc Provid AIDS Care. 2020;19:2325958219898457. doi:10.1177/2325958219898457
- Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51‐e77. doi:10.1093/cid/ciw118