Funding has been awarded to principal investigator Kenneth Mugwanya MBChB, MS, PhD by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (1R01HD123957-01) to test how to effectively integrate LEN PrEP implementation in maternal and child health clinics for pregnant and postpartum women at elevated risk for HIV and evaluate its impact on new HIV infections averted, extended safety data infant pre- and postnatal LEN PrEP exposure and assess birth and growth outcomes following LEN PrEP exposure through at least the child’s 1st birthday in the first large real-world LEN PrEP in pregnancy evaluation.
Abstract
In high HIV prevalence regions, women are at elevated risk for HIV during pregnancy and breastfeeding, and are priority population for HIV prevention. Despite widespread availability of oral HIV preexposure prophylaxis (PrEP), utilization is low especially during postpartum when more than 50% of young African women on PrEP discontinue due to daily pill adherence and stigma challenges. Twice-yearly injectable Lenanacapvir (LEN) PrEP was 100% efficacious in clinical trials among women and was safe and well-tolerated in pregnancy. LEN is recommended by the FDA and WHO as an additional PrEP option for pregnant/postpartum women at elevated HIV risk, while calling for additional safety surviellence during implementation. For pregnant women who choose LEN PrEP, three doses initiated in early pregnancy can offer coverage up to at least 6 months postpatum, highlighting the potential to significantly avert primary HIV infection and vertical transmission during periods of elevated risk. But LEN PrEP impact will depend on access and how well opportunity costs and health-system barriers can be navigated by clients.
Maternal and child health (MCH) clinics offer a trusted and routinely accessed setting for many pregnant and postpartum women to learn about and obtain PrEP. Our team pioneered oral PrEP delivery models in routine MCH clinics. We established feasibility, demonstrated safety, and identified barriers to integrating oral PrEP in MCH clinics. We are well to positioned to define effective models to deliver LEN delivery for pregnancy and breastfeeding women and additional surveillance of perinatal exposure outcomes. Building on our successful work with oral PrEP in MCH clinics and in collaboration with the Kenya ministry of health (MOH), we propose a hybrid pragmatic stepped-wedge cluster randomized trial to test sustainable effective delivery models and demonstrate impact of LEN PrEP in 12 real-world MCH clinics in two HIV high incidence counties prioritized for LEN roll-out in Kenya.
We will rigorously evaluate impact of adding LEN PrEP as an available PrEP option (oral F/TDF or LEN) on uptake, HIV prevention coverage, and new HIV infections averted among 1200 pregnant and postpartum women at elevated HIV risk (Aim 1). In Aim 2, we will enroll and follow a subset of pregnant women who choose LEN PrEP (n=200) in a nested cohort to robustly evaluate prenatal and post-natal LEN PrEP exposure and the frequency of adverse birth and infant outcomes up to at least child’s 1st birth day. In parallel with Aim 1, we will evaluate implementation outcomes and assess impact of integration on existing workflows, clinic, provider, and client-level factors, including client experiences, PrEP product choice and switch, and preferences (Aim 3).
These innovative studies will demonstrate significant public health impact and robust extended safety outcomes for LEN PrEP in pregnancy to advance scale up where it is needed most, while efficiently generating effective and sustainable real-world LEN PrEP implementation models that can be quickly adapted to communities most affected by HIV globally and in the US.