Multi-level considerations for optimal implementation of long-acting injectable antiretroviral therapy to treat people living with HIV: perspectives of health care providers participating in phase 3 trials

Abstract

Background Long-acting injectable antiretroviral therapy (LA ART) has been shown to be non-inferior to daily oral ART, with high patient satisfaction and preference to oral standard of care in research to date, and has recently been approved for use in the United States and Europe. This study examined the perspectives of health care providers participating in LA ART clinical trials on potential barriers and solutions to LA ART roll-out into real world settings. Methods This analysis draws on two data sources: (1) open-ended questions embedded in a structured online survey of 329 health care providers participating in the ATLAS-2 M trial across 13 countries; and (2) in-depth interviews with 14 providers participating in FLAIR/ ATLAS/ATLAS-2 M trials in the United States and Spain. Both assessments explored provider views and clinic dynamics related to the introduction of LA ART and were analyzed using thematic content analysis. The Consolidated Framework for Implementation Research (CFIR) was drawn on as the conceptual framework underpinning development of a model depicting study findings. Results Barriers and proposed solutions to LA ART implementation were identified at the individual, clinic and health system levels. Provider perceptions of patient level barriers included challenges with adhering to frequent injection appointments and injection tolerability. Proposed solutions included patient education, having designated staff for clinic visit retention, and clinic flexibility with appointment scheduling. The main provider concern was identifying appropriate candidates for LA ART; proposed solutions focused on patient provider communication and decision making. Clinic level barriers included the need for additional skilled individuals to administer injections, shifts in workflow as demand increases and the logistics of cold-chain storage. Proposed solutions included staff hiring and training, strategic planning around workflow and logistics, and the possibility of offering injections in other settings, including the home. Health system level barriers included cost and approvals from national regulatory bodies. Potential solutions included governments subsidizing treatment, ensuring cost is competitive with oral ART, and offering co-pay assistance. Conclusions Results suggest the importance of multi-level support systems to optimize patient-provider communication and treatment decision-making; clinic staffing, workflow, logistics protocols and infrastructure; and cost-related factors within a given health system.

Perspectives on preparing for long-acting injectable treatment for HIV among consumer, clinical and nonclinical stakeholders: A qualitative study exploring the anticipated challenges and opportunities for implementation in Los Angeles County

“…Facilitators to the implementation process included treatment education/support, and the development of LAI ART treatment guidelines/policies. Previous studies have found similar barriers to and facilitators of LAI ART implementation, and this study further highlights implementation barriers on the consumer and provider level that may not be entirely exclusive to LAI ART implementation [ 23 – 29 ].…”

“…structural characteristics and capacity of the organization, the organizational implementation climate, capacity for change, readiness for implementation aided by availability of resources and access to knowledge, and overall perceived relative priority of LAI ART in the HIV treatment continuum), individual characteristics (e.g., knowledge and beliefs about the intervention and personal attributes such as motivation to use LAI), and also the implementation process (characterized by plans to ease implementation and engagement of key stakeholders with critical roles in the implementation process). The CFIR has been previously used to study the implementation of new technologies and clinic-based interventions for PWH and to explore the system-level challenges and facilitators to the implementation of these interventions [ 29 , 42 , 43 ]. See Table 1 for identified themes and representative quotes within each CFIR domain.…”

“…The potential advantages of LAI ART for consumers may include convenience, increased confidentiality, and removal of the need for a daily routinized behavior (tablet-taking), as well as the avoidance of drug-drug interactions modulated by first-pass hepatic metabolism. Barriers for both providers and consumers include concerns around safety and efficacy, increased clinic visits (LAI ART obligates monthly injections, compared to recommendations for stable ART follow-up being semi-annually), burden to workflow and cost, and low perceived trustworthiness of the health care system and consequent mistrust of new treatments [ 23 – 29 ]. In particular, Black communities in the U.S., which are disproportionately impacted by HIV, have expressed high rates of mistrust of new medical interventions due to the impact of historical, structural and systemic racism and discrimination in healthcare delivery and medical research studies [ 30 – 37 ].…”

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

“…staff capacity and training, clinic capacity, cold chain), a patient’s perspective (i.e. injection tolerability, adherence to visits) and a pharmacological perspective (extended DDI, missed doses, pharmacokinetic “tail”) are all pressing needs to be met [ 101 ]. Additionally, the high BMI at the initial period post-BS may negatively affect the C trough of long-acting cabotegravir as seen in phase IIa trials [ 102 ], although the effect was not persistent until week 48 [ 103 ].…”

Impact of long-acting therapies on the global HIV epidemic

“…Due to high tuberculosis (TB) and hepatitis B (HBV) burdens, as well as cold chain requirements, currently available longacting formulations, are not ideal for LMICs. Other barriers to the optimal implementation of long-acting antiretrovirals in LMICs, include the increased frequency of the injection appointments, provider concerns of identifying appropriate candidates for LA ART and operational challenges of the availability of single use needles [15,16]. As these formulations, are shown to be safe, well tolerated, more user-friendly, and economically viable, they are likely to gain broader appeal.…”