Study methods are aligned with current systematic approaches to patient decision aid development [36,45,46], and will occur in 3 phases (Figure 1). Each phase is associated with 1 of the following study aims. Phase 1 will generate data to inform i.ARTs content using mixed methods research with WWH and providers. Phase 2 will iteratively develop i.ARTs as a web-based patient decision aid. Phase 3 will pilot test i.ARTs to assess feasibility, acceptability, and usability and to compare decisional outcomes and adherence data (including viral suppression, ART refills, and clinic attendance) between i.ARTs recipients and standard of care (control) WWH (n=180; 90 per group). Each phase includes distinct data collection activities, which are summarized in Table 1.

To ensure i.ARTs addresses a comprehensive array of factors that influence LAI ART uptake, phase 1 includes data collection that incorporates the perspectives of both WWH and providers at MWCCS sites.

Phase 1a will quantitatively assess WWH perspectives on LAI ART and decision making, identify relevant barriers and facilitators to LAI ART uptake, and identify the characteristics of women who are most likely to adhere to LAI ART. It utilizes survey data administered to the MWCCS study cohort starting in October 2020. Historically, this sample included 1661 WWH of whom 1610 have a history of taking oral ART [44]. None have participated in LAI ART clinical trials. Full descriptions of participant recruitment, selection, enrollment, and study procedures for MWCCS are available elsewhere [44]. Survey responses from the 2020 cohort were collected from fall 2020 through summer 2021, and include 15 items that assess LAI ART–related knowledge, interest, and potential barriers and facilitators to use. We will use multivariable logistic regression models to identify factors associated with WWH’s interest in, and barriers and facilitators to, LAI ART. While potential barriers and facilitators to LAI ART uptake can change over time (eg, transportation/housing), we will be looking at these associations cross sectionally and thus capturing these barriers at a given moment in time. The sample size provides the power to detect modest effect sizes in a multivariable logistic regression analysis (odds ratios ranging from 1.4 to 1.6), even with a low probability of LAI interest and a high squared multiple correlation (0.4-0.5) between predictor variables. This sample size will allow for subgroup analyses and still detect moderate effect sizes (eg, by age or MWCCS site).

Phase 1b assesses HIV provider perspectives on LAI ART for their female clients. It involves in-depth interviews with 30 medical (eg, infectious disease physicians, advanced practice registered nurses) and 15 social service providers (eg, case managers, HIV clinical social workers) who serve WWH across 9 MWCCS sites and affiliated clinical sites.

Provider participants will complete a 1-time, 45-60-minute interview, and receive a US $75 gift card as compensation. Interview domains will include (1) providers’ perceived characteristics of women most likely to adhere to LAI ART, particularly compared with oral ART (eg, housing, oral ART adherence, caregiving responsibilities, and clinic attendance); (2) reasons providers would not offer LAI ART to a woman for whom it is clinically indicated; (3) providers’ perspectives on decision making in the clinical setting and their experience in deciding which ART medications their WWH clients should take; and (4) multilevel barriers and facilitators to WWH’s ART use and solutions to overcome these adherence barriers. These domains are determined by formative work by the study team [18,20,22,23]. Interviews will be digitally recorded and professionally transcribed. Transcripts will be coded using a set of codes inductively identified from the data; these will be supplemented by codes derived from the existing literature. A thematic content analysis approach will be used to identify key findings within domains of interest [47]. Data will be summarized and applied to activities in phase 2, described in the following section.

Phase 2 utilizes sequential focus groups with both WWH and medical and social service providers to determine the content of i.ARTs and create and revise the i.ARTs web-based app. Existing research indicates that web-based decision aid tools have advantages over paper-based ones, including interactive interfaces and visual filtering and sorting options [48]. This stage of i.ARTs development will follow International Patient Decision Aids Standards Collaboration (IPDAS) guidelines [46,49,50] and use the Ottawa Decision Support Framework [27,51-53]. This framework explains the relationship between participants’ decisional needs and decisional quality using both prescriptive [54] (based on rational actions, highest expected utility) and descriptive [55] (preferences-based, nonrational) decision theories.

An overview of the planned i.ARTs development process is included in Figure 2. We will conduct 2 sets of 5 focus groups: 1 set with 10 MWCCS providers recruited from the Phase 1 interview participants and the other set with 8-10 WWH recruited from the Miami MWCCS–affiliated clinical site. The Miami MWCCS site was selected due to the city’s high HIV incidence and low ART adherence, as well as a racially/ethnically diverse population [56-58]. WWH will be selected from Miami’s MWCCS community advisory board as well as by local MWCCS collaborators to ensure inclusion of women with a diverse range of perspectives, clinic attendance, and adherence. Each focus group will meet for approximately 60 minutes, and participants will be compensated US $40 per session for their time. We will record and transcribe the focus groups and review them to identify which items and topics should be included in the patient decision aid, as well as how to word specific items.

Focus groups will use data from phase 1 to develop and finalize i.ARTs content and iteratively refine the web-based version of i.ARTs to prepare for the phase 3 pilot testing according to the schedule in Figure 3. Between each set of focus group meetings, the study team will integrate feedback from both the provider and WWH groups and either create the suggested content or make the suggested improvements to the i.ARTs program. This will ensure that women’s perspectives and realities will be captured to tailor the content within the patient decision aid.

This study received approval from the Columbia University Institutional Review Board (IRB; approval number IRB-AAAT5314), and we will receive approval from University of Miami IRB once the clinical trial portion begins.

This paper describes the protocol for developing and piloting the first decision aid to facilitate women’s decision making between LAI and oral ART modality for HIV treatment. This study will expand HIV treatment research in important ways. The field of HIV care has increasingly emphasized patient-centered care [42], as this approach improves quality of life, patient adherence, and health outcomes [28,42,71]. Patient decision aids are a key tool for patient-centered care, as they can enhance equity in medicine, activate patients to increase their knowledge and decision-making power, and lower medical paternalism [24,29-31]. They also enhance patient care by enabling shared discussions and outcomes that match patients’ needs [26,42,72].

As noted, patient decision aids have been successfully used in other areas of medicine, most similarly to this in facilitating contraception decision making among women [40,41]. However, as yet no patient decision aids exist to facilitate the decision-making process between oral and LAI HIV treatment. Thus, i.ARTs is urgently needed to promote equity in patient-provider decision making by helping WWH identify their preferences for oral or LAI ART. Further, developing i.ARTs specifically for women may help promote gender equity in the uptake of LAI ART. Examples from oral pre-exposure prophylaxis (PrEP) scale up show that a lack of decision aid tools can hinder uptake and lead to gender-related disparities [73-76]. Women not only have much lower rates of PrEP use than men but also have shorter periods of sustained PrEP use [75,77,78]. Our study to develop and pilot test the i.ARTs patient decision aid aims to prevent a similar gender gap for LAI ART uptake and thus a further exacerbation of disparities in care and treatment outcomes.

Furthermore, this study comes at a crucial moment in HIV treatment. As the menu of options for ART treatment expands, patients and providers will encounter different considerations and concerns regarding the various ART modalities. Despite LAI ART’s potential, we know little about the “real-world” facilitators and barriers WWH will face, or how providers will decide to whom to offer LAI ART. The FDA approved LAI ART in January 2021, and developing i.ARTs as LAI ART is rolled out has the potential to capture and address some of these real-world barriers and facilitators. In turn, it will provide data that can support the further dissemination of this new biomedical technology. In addition, i.ARTs can be updated to incorporate future ART modalities (eg, monthly oral medication [79,80], implants [81], subcutaneous injections [82]).

Our study has multiple strengths that ensure the validity and applicability of its findings. As described in the previous sections, we incorporate patient and provider perspectives throughout i.ARTs development (phase 1, phase 2) and testing (exit interviews in phase 3). This ensures that i.ARTs content includes the full landscape of factors that influence LAI ART uptake, determine whether LAI or oral ART best fits a woman’s values and preferences, and will help us to identify potential differences in patient and providers’ beliefs regarding who should be offered LAI ART.

Next, our real-world clinic-based sample can provide insight into LAI ART uptake that samples of clinical trials participants cannot. As mentioned, women were underrepresented in LAI ART clinical trials [10-13]. Working with women from the MWCCS not only resolves this gender gap, but also provides data that trial- and clinic-based samples (eg, CFAR Network of Integrated Clinical Systems [CNICS] sites) cannot, as it includes out-of-care women who may face different and additional adherence barriers. Clinical trials include participants with high adherence to determine drug efficacy, but only 49% of MWCCS women would be eligible for AIDS Clinical Trials Group trials [44]. Furthermore, pilot testing i.ARTs in Miami, which leads the United States in HIV incidence, and whose HIV epidemic is marked by stark racial and ethnic disparities, will help us identify the full landscape of WWH’s barriers to ART use and potential solutions to address them. This will increase the relevance of i.ARTs for WWH across the United States.

Finally, our study benefits from its mixed methods approach [83], which increases validity by capitalizing on each method’s inherent strengths. The different methods answer complementary research questions: we will use the phase 1 survey and provider interviews to explore potential disconnects between who may be offered LAI ART and who wants it, which can affect patient equity; interviews with women who choose LAI ART will explore the mechanisms that drive viral suppression data abstracted from EMRs. We will integrate mixed method findings using “triangulation” (ie, use of 2 different methods to address the same research question) to improve reliability [84,85]. Consistency of findings across methodological approaches increases validity and reliability and suggests findings are not due to methodological artifacts [86]. This will allow us to see how themes vary across methods, leading to stronger findings than using each method independently.

As this study is set in real-world clinical settings, we expect challenges to incorporating i.ARTs delivery into existing clinical workflows. These include considerations such as available space for participants to complete i.ARTs, tech support for the computerized tool and printout, staffing resources, and limited clinician time with each patient to discuss the decision aid results. The study team will work with the clinic staff to determine how to ensure efficient delivery of i.ARTs in the clinical setting. Exit interviews will be used to collect data on these challenges to inform further scale-up or dissemination efforts of i.ARTs outside of the Miami-based clinic.

As LAI ART is being administered in a real-world setting, participating clinicians are subject to existing, and possibly changing, FDA approvals. While phase 3 trials are currently testing LAI ART for nonadherent patients, the FDA-approved LAI ART formulation is only for virally suppressed patients. To ensure i.ARTs incorporates all relevant drivers of ART use for all women, we aim to include nonadherent women in aim 3, pending FDA approval. If FDA approval only exists for virally suppressed WWH when aim 3 starts, then we will limit the pilot test to that population. Should FDA approval for nonadherent patients begin in the middle of the pilot, we may adjust eligibility criteria to ensure a standard participant population throughout the pilot period. The study team will carefully monitor developments in ART treatment technologies and adapt accordingly. In addition, LAI ART was initially approved as a monthly injection, and the US FDA has approved a bimonthly (ie, every 8 weeks) formulation of LAI ART. This may also affect women’s preferences as the study is rolled out.

New modalities of ART delivery may emerge prior to the pilot study period, including monthly oral medication [79,80], implants [81], and subcutaneous injections [82]. The addition of these new technologies could further complicate the decision-making process. As mentioned earlier, the i.ARTs tool is web based and thus easy to update as technology or treatment modalities change [87]. The web-based nature of this tool will allow us to adapt and expand i.ARTs to all genders in future studies. In addition, a similar approach could be used to develop a tool to facilitate women’s decision-making process between oral and LAI versions of PrEP, with a goal to limit HIV infections among women.