Tonse Pamodzi: Developing a combination strategy to support adherence to antiretroviral therapy and HIV pre-exposure prophylaxis during pregnancy and breastfeeding

To eliminate mother-to-child transmission of HIV (EMTCT), scalable strategies to enhance antiretroviral adherence for both antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are needed as part of integrated HIV and maternal-child health services. We developed Tonse Pamodzi (“all of us together”), an adaptable intervention integrating biomedical and behavioral components to support HIV treatment and prevention. We describe our intervention development process, which comprised formative qualitative research, a review of the literature, and technical input from stakeholders representing the community, health systems, and policymakers. The resulting intervention, described herein, integrates patient-centered counseling and engagement of a patient-selected adherence supporter for pregnant and breastfeeding women initiating ART or PrEP. Patients receiving the intervention engage in Integrated Next Step Counseling (iNSC) sessions delivered by trained counselors to build and maintain adherence skills. Each patient also has the option of selecting an adherence supporter (partner, family member, or friend) who may participate in iNSC sessions and provide adherence support outside of these sessions. This flexible intervention is adaptable not only to ART or PrEP use, but also to the needs and preferences of each woman and the clinical context. If shown to be acceptable and feasible, the Tonse Pamodzi intervention may be an important tool in continuing efforts for EMTCT. The Tonse Pamodzi intervention is aligned with our overarching framework for HIV prevention during pregnancy and breastfeeding [43]. We posit that, in order to optimally reduce horizontal and vertical HIV transmission, strategies tailored to the HIV status of the patient and her partner(s) are needed. Although the armamentarium for HIV prevention is growing, antiretroviral medications remain foundational biomedical interventions, whether for HIV treatment (ART) or prevention (PrEP). To strengthen HIV treatment and prevention services for pregnant and breastfeeding women, we sought to develop a status-neutral intervention to enhance antiretroviral adherence through an adaptive and integrated approach. Our intervention development process included a formative qualitative study, stakeholder consultation, and identification of intervention components through expert consultation and literature review. We describe each of these activities below. We conducted formative research to inform the design of our adherence support strategy. At sites in Lilongwe, Malawi and Lusaka, Zambia, we completed a total of 143 in-depth interviews with various groups, including pregnant and breastfeeding women, male partners, healthcare workers (HCWs), and policymakers. Several findings from these interviews informed the intervention. First, participants emphasized the important role of social support for medication adherence, especially from male partners. This desire was embedded in social and cultural norms, and was a key factor in women’s medical decision making. Second, among many participating women, there were formalized ways in which male partners provided adherence support. This included providing reminders about clinic appointments and, for women who were HIV-positive and on ART, supporting adherence and assisting with medication collection. Participants offered suggestions about how such engagement could be increased, including structured involvement in clinical care. Third, with the exception of policymakers, PrEP was not well-known to most groups. This was not surprising since PrEP had only recently been introduced (in Zambia) or in early policy discussion (in Malawi) at the time of the study. Nevertheless, patients viewed PrEP positively; many indicated that, if made available, they would be interested in initiating PrEP. However, a common concern was the need for strict adherence and how this would be maintained over time. HCWs and policymakers also emphasized the need for resources—and new approaches—to promote PrEP adherence at the clinic level. Complete qualitative results have been published elsewhere [34, 44]. For the formative qualitative study above, we received ethical approval from the University of North Carolina at Chapel Hill Institutional Review Board (Chapel Hill, NC, USA), the National Health Science Research Committee of Malawi (Lilongwe, Malawi), and the University of Zambia Biomedical Research Ethics Committee (Lusaka, Zambia) to conduct this study. All participants provided written informed consent prior to initiating study activities. We synthesized the formative findings alongside results from mathematical modeling and systematic reviews [22, 45, 46] to develop an HIV prevention package for pregnant and breastfeeding women. To facilitate this process, in September 2018, we convened a technical consultation with stakeholders representing the community, health systems, and policymakers. Participants included our study team, steering committee, and invited experts from the U.S., Malawi, Zambia, and South Africa. The objectives of this two-day meeting were to review ongoing research in HIV prevention during pregnancy and breastfeeding in Zambia and Malawi—including our formative work—and vet proposed interventions for our target population. Our panel identified potential obstacles to ART and PrEP adherence for pregnant and breastfeeding women, including barriers at the individual, relationship, and structural levels. These were based on the existing medical and public health literature. Intervention approaches, including patient-centered counseling and external social support for adherence, were identified which could address each barrier (Table 1). Additional key stakeholder recommendations for our intervention included: (1) adaptation of services to promote male engagement; (2) integration of new services within existing structures; (3) promotion of awareness for newly introduced prevention modalities, including PrEP, and (4) consideration of structural and behavioral barriers to antiretroviral drug adherence. From the formative study and stakeholder recommendations, a patient-centered adherence counseling approach emerged as a foundational component of the intervention. As motivational interviewing and other patient-centered counseling had been evaluated in the context of HIV prevention and treatment, we sought to adapt an evidence-based strategy to address ART and PrEP adherence. We consulted with experts in HIV adherence and reviewed counseling approaches familiar to the study team. Through this process we identified the Integrated Next Step Counseling (iNSC) approach for adaptation. This patient-centered approach had been used in the context of HIV; was found to be acceptable and appropriate for the target population; and retained sufficient flexibility to address challenges faced with both ART and PrEP [47, 48]. To foster external adherence support as part of our intervention, we conducted a literature review focusing on couples-based and other social support-based behavioral interventions to support adherence to ART or PrEP. Relevant interventions were identified through a systematic search of PubMed, Clinicaltrials.gov, and the Centers for Disease Control and Prevention (CDC) Evidence-Based Intervention database, and through content expert recommendation. The search yielded 17 unique interventions and revealed mixed evidence of effectiveness. Examples of diverse models for adherence support interventions spanned three basic categories of support: couples-based support for adherence; support from an individual selected by the patient (often a family member or friend); and support from a “peer” assigned by the study, often another patient. We identified the programs in Table 2 as those most salient for our intervention objectives and context, prioritizing interventions with one or more of the following characteristics: evidence of a treatment effect on adherence or intervention acceptability/feasibility; appropriateness to the African context; and potential for scalability and sustainability in low- and middle-income country settings. Common features that were incorporated into these interventions included the selection of an adherence supporter with an existing relationship with the patient and integration of individual counseling and dyadic support options. We sought to develop a unified approach to support both ART and PrEP adherence. Based on our formative work and the recommendations from the technical meeting, we adapted and developed two intervention components: (1) tailored patient-centered counseling focusing on adherence and sexual health and well-being, and (2) external adherence support. These strategies addressed many barriers identified in our technical consultation (Table 2) and could be tailored for either ART or PrEP. To enhance facility-based adherence support, we adapted an existing counseling approach: Integrated Next Step Counseling (iNSC) [47, 48]. iNSC is a patient-centered, highly tailored approach to adherence support and has been used in previous clinical trials [47, 48]. It comprises nine key steps that engage the patient and ensure that discussions are interactive, targeted, and actionable. iNSC incorporates motivational interviewing techniques and draws upon the Information, Motivation, Behavioral Skills model [52, 53]. Given the prominence of external adherence support in our formative research and literature review, clinic-based iNSC was paired with an adherence supporter intervention. The adherence supporter component of our intervention draws upon common elements of relevant prior interventions identified in our literature review, including: selection of a supporter with an existing relationship with the patient; facilitating lay adherence support through a brief orientation; and involving the supporter in dyadic adherence support counseling sessions. This intervention component was informed by social support theories, which suggest that such support can bolster coping efforts [54], facilitate problem solving, and provide access to essential information and resources to support health behaviors including medication adherence [55, 56]. Specifically, we aimed to operationalize dimensions of social support described by House [57]: emotional support, instrumental support, and informational support. We documented the content for each component of the Tonse Pamodzi intervention in an iteratively developed intervention manual. A core study team adapted existing iNSC manuals to address the needs of pregnant and breastfeeding women using PrEP or ART. This team also created the training and counseling content involving the external adherence supporter, including an orientation session for the supporter and joint iNSC sessions. Study team members met regularly to refine the intervention manual and sought input from study counselors in structured ways to address feasibility and acceptability. After developing the initial intervention manual, changes were made based on feedback from study counselors and audits of early intervention sessions. During a three-day training, study counselors gave their feedback on the intervention manual and recommended that we focus on addressing the general wellbeing of women newly diagnosed with HIV during the first iNSC session. They also suggested that the discussion of adherence supporter selection follow the first iNSC session (rather than being integrated into the session itself). Finally, they proposed that the roles for iNSC counseling and adherence supporters be separated, to ensure the confidentiality of the information shared by the participant. Following the training, the intervention development team demonstrated sessions and counselors piloted the intervention manual by role playing in pairs. These sessions were audio-recorded, transcribed, and translated to English. The intervention development team provided feedback on these transcripts as well as transcripts of the first two iNSC sessions conducted by each counselor. Through this process, we observed a tendency toward counselor-directed prescriptive education rather than participant-centered counselling as intended. As part of our ongoing training, case scenarios and role plays were conducted to improve counselling style and ensure fidelity to the intended the patient-centered nature of iNSC counselling. In early intervention sessions, some participants were confused by requests to make decisions to tailor their care (e.g., nomination of an adherence supporter). The counselling approach was adjusted to emphasize to women that they had agency to determine the course of the intervention, a paradigm shift from typical health care discussions in the study setting, but a shift which most women embraced. The intervention manual was finalized based on these recommendations and lessons learned. Below, we describe the content of the final intervention components, which are under evaluation in an ongoing pilot study. The full intervention manual is included as S1 Appendix.