Exploring early implementation factors related to novel PrEP formulations for pregnant and postpartum women in Kenya

Abstract

New long-acting HIV pre-exposure prophylaxis (LA-PrEP) methods offer a promising solution to adherence challenges among pregnant and postpartum women at high risk of HIV. These options provide an alternative to daily oral PrEP, which can be difficult to maintain, particularly during pregnancy and postpartum. Despite their potential, evidence on preferred LA-PrEP attributes and acceptability in maternal and child health (MCH) systems remains limited. In high HIV-burden settings, pregnant and postpartum women face nearly double the HIV prevalence of the general population, underscoring the urgency of person-centered HIV prevention strategies. While LA-PrEP modalities demonstrate efficacy in HIV prevention and evidence of safety during pregnancy and lactation is increasing, unique considerations exist for their integration into reproductive health settings. However, implementation data are scarce. To address these gaps, we addressed the following research objectives, 1) to identify the preferred attributes of PrEP among pregnant and postpartum women at key timepoints in the perinatal period and explore how these preferences can inform health planning to expand PrEP choices for this population, 2) to assess the acceptability of long-acting PrEP methods among pregnant and postpartum women and determine strategies to enhance their acceptability in this population, and 3) to examine the potential barriers and facilitators to implementing long-acting PrEP for pregnant and postpartum women in Kenya and identify necessary adaptations and strategies for successful implementation, we evaluated LA-PrEP acceptability, identified potential barriers and facilitators, and explored strategies to enhance its adoption in MCH systems.For the first study, we conducted a discrete choice experiment (DCE) among HIV-negative pregnant and postpartum women in Kisumu and Siaya, Kenya, enrolled between 24-32 weeks gestation and who had a high HIV risk score. Participants completed the DCE with 12 choice sets at their 3rd antepartum and six-month postpartum visits. Attributes included effectiveness, form and dosing, safety data, side effects, collection place, cost, and multipurpose prevention (postpartum only). We fit effects-coded choice data to a conditional logit model, latent class analysis (LCA) for preference heterogeneity, and univariate multinomial logistic regressions to predict class membership by individual characteristics. A total of 512 women completed the DCE (151 pregnant, 509 postpartum). Bimonthly injections were strongly preferred, showing the highest positive utility (pregnant: 1.22, 95% CI: 1.12–1.33; postpartum: 1.24, 95% CI: 1.18–1.30). Four latent classes emerged: "Flexible PrEP Adopters" (37.2%), "Safe and Effective Injection Preference" (16.5%), "Strong Injection Preference" (37.7%), and "Oral PrEP Preference" (8.6%). Higher parity was associated with lower odds of membership in "Flexible PrEP Adopters" (OR=0.6, 95% CI: 0.4-0.8, p=0.001), "Safe and Effective Injection Preference" (OR=0.6, 95% CI: 0.4-0.8, p=0.003), and "Strong Injection Preference" (OR=0.7, 95% CI: 0.5-1, p=0.027) compared to "Oral PrEP preference". For our second study, we conducted an exploratory qualitative study with postpartum women in five public health facilities in Kisumu and Siaya Counties, Kenya. In-depth interviews (IDIs) were conducted with women expressing high, low, and mixed LA-PrEP interest throughout pregnancy and postpartum. Inductive and deductive content analysis was used, and themes of acceptability were explored using the Theoretical Framework of Acceptability (TFA). We conducted 70 IDIs with postpartum women between August 2023 and March 2024. The majority (62.9%) expressed consistently high interest in LA-PrEP. Most viewed LA-PrEP, especially every two-month injectables, as highly acceptable due to reduced pill burden, side effects, and dosing frequency. Concerns were raised regarding injectable PrEP safety for the baby during pregnancy and suitability of using the vaginal ring during delivery. Participants emphasized the importance of education on the safety of these methods during pregnancy and breastfeeding, and strategies for improving adherence, such as mobile reminders. Overall, women preferred LA-PrEP options over daily oral PrEP for convenience, effectiveness, and privacy, with healthcare provider education seen as crucial. For our third study, we conducted a qualitative study using focus group discussions (FGDs) with healthcare workers and other key opinion leaders related to PrEP delivery for pregnant and postpartum women. Interview guides were informed by the EPIS and CFIR frameworks. HCW FGDs included an activity to prioritize information, training, or support strategies for LA-PrEP provision. We used a rapid qualitative analysis to identify facilitators and barriers to integrating LA-PrEP into reproductive health settings and matched potential implementation strategies. A total of 9 FGDs were conducted with 45 individuals between August and October 2023 (5 FGDs among HCWs and 4 among CAB members). They identified interconnected determinants including training, funding, personnel, and community sensitization. Some strategies clearly addressed barriers (e.g. training). However, some barriers had no clear solution, such as LA-PrEP drug availability and access to funds to conduct training and community sensitization. The prioritization activity revealed common resources needed for LA-PrEP implementation (e.g., national guidelines, training, and personnel), but importance varied by location. A wide range of implementation strategies were identified, such as financial incentives for transportation, using community health providers to conduct community sensitization, and integrating LA-PrEP into FP clinics. In summary, we found strong preferences for bimonthly injectables, which emphasized the need to prioritize LA-PrEP in this population. ANC settings can support diverse PrEP preference profiles with tailored counseling to account for individual preferences, PrEP experience, and obstetric history. We also found high acceptability of LA-PrEP options among postpartum women with experience taking PrEP during pregnancy, underscoring diverse preferences and key factors influencing acceptability, including safety, discretion, and convenience. HCW and CAB members were optimistic about the promise of new LA-PrEP options and identified important barriers and strategies for consideration. Future research should consider prioritizing implementation strategies and evaluating the impact of strategies on implementation barriers. This dissertation emphasizes the importance and potential impact of offering LA-PrEP options to pregnant and postpartum women.