Introduction

The Joint United Nations Programme on HIV/AIDS (UNAIDS) has widely promoted the goal of ending the HIV/AIDS epidemic by 2030 [1]. To help achieve this goal, antiretroviral therapy (ART) modalities that do not require daily dosing might be an important strategy to improve viral suppression and maximize treatment outcomes for persons with HIV (PWH) who struggle to adhere to daily oral ART [2,3]. Long-acting injectable (LAI) ART is a novel alternative to daily oral pills [4]. The combination of once monthly or every-two-months long-acting cabotegravir and long-acting rilpivirine has been approved for use in the United States and Europe as treatment for adolescents and adults living with HIV who are virally suppressed (HIV RNA < 50 copies/ml) [3,5,6], and registration processes are ongoing in other parts of the world [7]. Findings from phase 3 clinical trials found that LAI ART (hereinafter referred to as “LAI”) is non-inferior to daily oral ART [8,9]. This new modality holds great potential to revolutionize treatment for millions of PWH by decreasing the daily pill burden from 365 days to only a few injections per year [4]. LAI may reduce treatment fatigue due to high pill burden, improve adherence, and reduce HIV-related stigma due to its discreet treatment [10–12].

LAI is more expensive to produce and deliver relative to oral treatments. Consequently, cost is an important structural barrier to widespread LAI use [12,13]. The high costs of LAI may make it essential to prioritize LAI for populations who will benefit the most from this regimen, particularly in more resource-constrained settings. So far, phase 3 LAI trials have been restricted to PWH with good adherence to daily oral ART, evidenced by viral suppression [8,9]. But LAI appears to be cost-effective if explicitly targeted to PWH who would be expected to have viral failure on oral ART due to inadequate adherence [14]. Hence, scale-up of LAI will introduce novel decision-making considerations among policy makers, clinicians, and patients.

As LAI becomes approved for use, careful preparation is needed to introduce LAI efficiently, equitably, and acceptably, especially in low resource settings where availability of LAI may be limited. Yet the attitudes of stakeholders and PWH regarding priorities for LAI use are unknown and it is unclear whether and how the implementation of LAI should be regulated with these considerations in mind. For example, should LAI be prioritized for PWH with predicted challenges to viral suppression or only those with demonstrated failure? And who gets to decide whether LAI is right for a particular person? Among people who might benefit from LAI, people who inject drugs (PWID) living with HIV are unique. PWID often struggle with adherence and might benefit from regimens that do not require daily adherence [15]. Indeed, injection drug use is a strong risk factor for suboptimal ART adherence globally [15–17]. But PWID are frequently excluded from LAI clinical trials. As a result, the appropriate way to consider injection drug use behaviors in LAI decision-making is unclear.

In Vietnam, PWID are the predominant group of PWH [18]. Vietnam is also one of six countries accounting for half of the global population of PWID, and the HIV prevalence among Vietnamese PWID is 29.3% [19]. Vietnamese PWID with HIV may benefit from LAI, but preferences and demand are not known. Although LAI has not yet been approved for HIV treatment in Vietnam, approval is expected soon. We conducted a qualitative study among PWID with HIV, ART clinicians, and policymakers in Vietnam to explore their perceptions on patient prioritization and decision-making for LAI.

Methods

Results

All invited participants agreed to participate. In sum, we conducted 38 IDIs with three groups of stakeholders (19 PWID with HIV, 14 ART clinic staff, and 5 HIV/AIDS policymakers). Among PWID with HIV, 3 (16%) were ART naïve, 14 (74%) were currently on ART and 2 (11%) had dropped out of care. The mean age of the PWID participants was 41 years old (range 34–47); 90% were male. The mean duration of time since HIV diagnosis was 11 years. ART clinic staff included four (29%) prescribing physicians, three (21%) counselors, three (21%) pharmacists, and four (29%) clinic directors. Among 5 policymakers, 2 were staff of the Vietnam Administrative for AIDS Control, and 3 worked at the Hanoi Department of Health or Centers for Disease Control. The IDIs lasted between 45 and 60 minutes.

Discussion

With existing and anticipated approvals of LAI for HIV treatment globally, policymakers, providers and their patients may soon be able to choose between traditional oral regimens and newer LAI options. Unlike a new oral regimen, LAI represents a substantial divergence in terms of health system, clinic, and patient logistics, convenience, and cost. More frequent clinic visits, the potential pain of injections, evolving supply chains, and the expense of LAI all mean it is unlikely to immediately or completely replace oral ART, although many patients and providers desire an injectable therapy option [20–23].

Identifying suitable or “preferred” candidates for LAI is a major barrier to implementation at the provider level [13,24,25]. Providers from ART clinics have had mixed opinions on whether adherent or non-adherent patients would be preferred for LAI [24,25]. In this study, we shed light on perceptions regarding patient/provider interactions regarding treatment choice and the policy structures that may inform these options. We focused on PWID with HIV, a group that commonly has worse treatment outcomes [15,16,26]. From our findings, PWID tended to rely on medical authorities to decide for them when it came to HIV treatment. In contrast, HIV providers would prefer to let clients make their own choice. This “choice” was contextualized as having to depend on whatever the forthcoming written guidelines from the Vietnamese government outlined as appropriate criteria for LAI. Policymakers, on the other hand, emphasized the importance of equal access to HIV treatment, arguing that no specific predefined group of clients should be prioritized or receive more attention than others. These conflicting opinions seemingly complicate selecting candidates for LAI when it is taken to scale in Vietnam.

When it comes to LAI, cost is a critical consideration, and those participating in our study raised important questions about the financial components of introducing LAI as a treatment option. Although drug costs have not been determined in settings where LAI has not yet been registered, the regimen is expected to significantly exceed the cost of oral ART for the near future [27,28]. Even as drug costs decrease with more widespread LAI use, additional resources are expected with more frequent visits and other associated consumables. High cost is an important hurdle for LAI implementation in low- and middle-income countries (LMICs) [13], and prioritization of patients to receive LAI might be unavoidable. In our study, the issue of costs did not come up during the interviews as a factor to decide which groups should be prioritized to use LAI, but costs were identified as a substantial barrier and have been described in a previous publication [12]. The most cost-effective approach appears to be to offer LAI to the subgroup of PWH having difficulties achieving adequate adherence and viral suppression with daily oral ART [14,29]; this approach prioritizes the benefits of improving viral suppression. Although not explicitly modeled, this strategy would also be expected to result in reduced transmissions and avoid some of the costly transitions to second- and third-line oral ART regimens for persons who develop resistance due to inconsistent adherence. For example, although different scenarios for introduction of LAI could potentially avert disability-adjusted life year (DALYs), only the use of LAI among those with a viral load great than 1000 copies would be cost-effective [14]. A more complete understanding of which PWH will benefit most from LAI given different levels of adherence and viral suppression is urgently needed.

PWID may be one group that needs to be prioritized based on historically poor viral load outcomes, but some of our participants raised the concern that prioritizing them risks further stigmatizing this group. Moreover, the idea of prioritization was not fully embraced by policymakers in Vietnam. An alternative to group-based prioritization is making prioritization decisions based on clinical criteria, such as viremia, though the individual and public health implications of “waiting for viral failure” must be considered. Additional research is needed to identify culturally acceptable prioritization strategies that balance the potential stigma, individual, and public health benefits with the economic constraints of this more expensive treatment modality.

In many LMICs, ART adherence among PWID is below the minimum level required for viral suppression [30]. PWID in Vietnam have significantly poorer immune reconstitution and retention rates, compared to those without injection drug use [26]. Nonetheless, as participants explained in our study, even though the burden of daily pills might be alleviated for clients receiving LAI, these patients still must adhere to clinic appointments to receive monthly or every-two-month injections. Missing injection appointments might cause more serious consequences than missing an oral dose, with both individual and public health implications if persons fail with resistance to the common backbone integrase strand inhibitor [31]. Tracing systems, appointment reminders and integration into other services such as methadone maintenance treatment are possible solutions to overcome this issue of missed appointments.

In general, clinic staff in our sample supported the model of shared decision making, in which both medical providers and patients share information and decide together. Among PWH, shared decision making has been associated with better outcomes, such as higher satisfaction and better treatment adherence [32]. But shared decision making may not be embraced by all patients. The PWID with HIV in our study seemed to be more confident and familiar with a provider-driven model, during which patients passively consent to professional authority and agree to the doctor’s choice of treatment. They assumed that they have no power and doctors will make the best choice for them. Indeed, the healthcare context in Vietnam traditionally emphasizes hierarchal authority above provider-patient partnership [33]. PWID living with HIV in Vietnam may be unaccustomed to making decisions about their treatment modality because for their HIV and substance use treatment, daily oral ART and methadone maintenance treatment have historically been the only options offered [12,34]. In a multi-country Asian study among persons with cancer, most Vietnamese patients perceived themselves as having no role in the decision making process, and the proportion of patients in Vietnam who considered themselves being more involved in decision making than preferred was also the highest, when being compared with other Asian countries [33]. These findings might reflect socio-cultural norms related to medical care in lower income countries [33,35]. Healthcare providers should therefore engage patients in discussions to explore their decision-making expectations and provide care according to their preferences.

Among patients who favor shared decision making, patient decision aids could be used to facilitate the process [36]. As participants mentioned in the interviews, shifting from one regimen to another might be necessary during the treatment process. Decision tools that inform choices regarding initiation, discontinuation of LAI, as well as changing between LAI and oral ART would be important to help both clinicians and patients make the best choice. Recommendations on eligibility criteria, patient prioritization, risks and benefits of LAI at the global and national levels based on strong evidence would also be warranted to provide guidelines for clinicians and ensure consistent practice across countries and regions.

In this study, we were able to invite and conduct in-depth interviews with policymakers at the Vietnam Administrative for AIDS Control, Ministry of Health, who would be involved in changing and issuing HIV policies for the country. However, like most countries, the HIV policy-making process in Vietnam is complex, involving many agents including the Communist Party, the National Assembly and the Ministry of Health, and other national and international agencies with diverse objectives and priorities [37]. As such, our results reflect an important but narrow perspective of HIV policymakers who would be expected to influence guideline development and implementation.

Just as policymakers reflect diverse perspectives PWH occupy a similar range of lived experiences when it comes to ART use and preferences. Our recruitment strategy, using the clinics to identify PWID who were living with HIV, meant that we were frequently limited to those who were engaged in care. We did intentionally limit the number of PWH who were ART naïve as we assumed they had less experience with ART in general, and thus may have struggled to respond to questions regarding barriers or challenges with the standard of care oral ART. We did intentionally recruit PWH who had disengaged in care but, given our clinic-based recruitment, the vast majority (all but two) of PWH were engaged in care at the time of our interview. Perceptions of LAI for PWID living with HIV who were on ART but subsequently stopped may differ from those who are durably engaged in ART care, and are not well represented in the current study. In addition, the absence of viral suppression data for patient-participants, which may have provided additional context for interpreting their experiences and perspectives. Studies with a larger and more diverse sample of PWID with HIV and additional key informants from governmental and non-governmental agencies contributing to HIV management guideline development and programming, may provide important additional insights. Another limitation of this study is that the data were collected in 2021, and perceptions of long-acting injectable (LAI) HIV prevention and treatment may have evolved since then, particularly with the growing global experience and awareness of newer agents such as Lenacapavir. Future research is needed to capture how these views may shift over time as LAI options become more widely available and integrated into HIV care in low-resource settings. Despite this, our findings still provide valuable insights into the attitudes and considerations surrounding LAI at the time of data collection, which can inform ongoing and future research on patient preferences and implementation strategies.

Conclusions

Our study provides unique and previously unexamined perspectives of LAI implementation and patient prioritization in an often overlooked key population of PWID living with HIV, through which we identify and expose critical complexities in the effort to balance equality and access with the reality of resource constraints.

Among PWID with HIV and HIV clinic personnel in Hanoi, Vietnam, LAI is a highly desirable treatment alternative to daily oral ART. Its unique advantages over oral ART may reduce barriers to viral suppression and facilitate achievement of the UNAIDS 95-95-95 goals [1]. But sustainable implementation, particularly in LMICs, will need to consider the resources associated with this novel treatment. The cost implications of LAI might create a challenging situation in LMICs, where demand is greater than supply, especially if many clinicians and PWH prefer LAI over daily pills. By exploring perceptions related to patient prioritization and selection among PWID with HIV, ART clinic staff, and policymakers in Vietnam, we identified implementation barriers related to the prescription of LAI by providers and uptake of LAI by PWID. We identified a need for a more nuanced approach to LAI implementation to ensure both efficiency and equality for PWH. Differential service delivery, shared decision making supplemented by decision aids, and guidelines for LAI prescription and patient selection may all be necessary to maximize treatment outcomes and bring this innovative treatment tool to scale.

Supporting information

Acknowledgments

We would like to thank the participants for their time and for sharing their experiences.