Editorial on the Research Topic Improving the delivery of pre-exposure prophylaxis (PrEP) to eliminate vertical HIV transmission

HIV pre-exposure prophylaxis (PrEP) significantly reduces new HIV infections (1). Among pregnant and lactating cisgender women in high HIV prevalence settings PrEP offers dual benefits for maternal and infant HIV prevention and is increasingly integral to vertical transmission prevention programs (2, 3). Many countries in East and Southern Africa with high HIV burden have integrated oral PrEP into HIV prevention programs (4), in the form of daily oral tenofovir disoproxil fumarate (TDF) containing regimens. While daily oral TDF-based PrEP use in pregnancy and lactation is considered safe and effective (5), only recently are data on PrEP implementation and extended safety emerging (6–8). As additional PrEP options become available (9), there is a need for more evidence on how to ensure effective antenatal and postnatal use (10).

Because of its high relevance to public health—and to global goals to eliminate pediatric HIV—we sought to highlight new research in this field. The result is this collection, which includes 13 articles of work done in sub-Saharan Africa (South Africa, Kenya, Eswatini, Zambia, Malawi, Lesotho, and Uganda) and the United States, demonstrating the importance of the topic globally. This body of work followed four major themes: (1) client knowledge, attitudes, and beliefs about PrEP (2) the PrEP care continuum, (3) healthcare provider experiences and attitudes and (4) PrEP safety, effectiveness, and delivery in pregnancy (Table 1). This work spanned the periconceptional period, pregnancy, and lactation. From this collection, we take away important lessons that will assist in advancing the field of PrEP provision of pregnant and lactating people.

Firstly, community PrEP education is critical to reducing stigma and increasing support for PrEP. Three studies explored PrEP knowledge, attitudes, and beliefs among pregnant and postpartum women and their partners. PrEP was viewed as safe and effective; however, Hamoonga et al. highlighted important concerns about side effects and potential negative impact on pregnancy and infant health. Fear of stigma was an important determinant of effective PrEP use with women without HIV including concern that partners or the community may perceive women as living with HIV or having multiple sex partners. In Eswatini (Khumalo et al.), PrEP awareness was high but accurate PrEP knowledge was incomplete. Young et al. identified PrEP misconceptions among clients who reported that PrEP improved health and could be used to treat sexually transmitted infections. Partner support was identified across several studies as a key determinant of PrEP uptake and continuation. Having a partner living with HIV was a major reason for initiating PrEP and was associated with higher adherence to both PrEP and ART. Routine data from Lesotho (Masenyetse et al.) identified a 2-fold higher follow-up among PrEP users in relationships where one partner was living with HIV. Similarly, having multiple sex partners was a common reason for PrEP use and a determinant of PrEP continuation.

Secondly, we learned about barriers and facilitators of the PrEP care continuum. Previous work has highlighted significant challenges with PrEP adherence which is critical for efficacy (11). Khadka et al. found that over 80% of pregnant adolescent girls and young women initiated PrEP in the first antenatal care visit. However, PrEP continuation reduced significantly with time and was <40% at 6-months despite the high prevalence of STIs. Similarly, Masenyetse et al. found that 40% of PrEP initiators in routine care among pregnant and postpartum had no follow-up visit, signally that barriers to PrEP continuation persist. Hurwitz et al. estimated overall PrEP adherence at 63% and identified several patterns of PrEP adherence during periconception among HIV-exposed South African women. Changes in perceived HIV risk over time may impact PrEP adherence; however, the large drop-offs and poorer PrEP persistence among women who become pregnant while on PrEP are concerning.

Thirdly, we derive insights from healthcare providers' experiences in delivering PrEP. Among providers who had no training or experience delivering PrEP (Pleaner et al.), there were significant concerns about burdening already busy clinics and the impact on other service delivery. However, in Kenya (Wagner et al.), among providers with experience delivering PrEP, delivery was viewed more favorably, as adaptable and meeting patient needs. However, PrEP delivery required provider training, was more complex compared to other services and required additional resources (Hicks et al.). Additionally, daily dosing for PrEP requiring frequent refills and access to services (e.g., long distances to clinics and waiting time) were important barriers (Hamoonga et al.). Sila et al. found that an intervention package including video education, HIV self-testing, and PrEP dispensing delivered at maternal and child health clinics significantly increased the proportion of clients counselled about PrEP and client satisfaction but was associated with increased waiting time. These findings demonstrate the need for continued research to optimize PrEP delivery.

Finally, this collection addresses PrEP effectiveness and safety in pregnancy. Fairlie et al. reviewed data on the safety profiles of available PrEP candidates including oral TDF-containing regimens, long-acting cabotegravir and the dapivirine ring. Except TDF-containing regimens, safety data on other PrEP agents is very limited in pregnancy and postpartum. They also reviewed existing drug surveillance systems in high- and low-income settings and suggested that PrEP surveillance be integrated into multiple surveillance systems. While the cost of building such systems is high, they argue that the extent of PrEP use warrants investment. Scott et al., found an increase in tenofovir/emtricitabine drug clearance throughout pregnancy, suggesting current dosing schedules may be inadequate to provide protective drug levels. Zewdie et al. found significant bone mineral density loss among pregnant women using oral TDF-based PrEP, which was likely attributed to pregnancy and not PrEP. This study was limited by small numbers of pregnant women not exposed to PrEP. Additional research is needed for robust comparisons between PrEP-exposed and unexposed populations.

In conclusion, this collection highlights important gaps in PrEP delivery among pregnant and lactating people. Ongoing discovery research will likely address pharmacokinetics and expand PrEP options; however, understanding how to scale-up PrEP delivery will require continued evaluation and adaptation to meet the needs of pregnant and postpartum women and in different regions.