Emerging evidence from a systematic review of safety of pre‐exposure prophylaxis for pregnant and postpartum women: where are we now and where are we heading?

Abstract

Introduction HIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre‐exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout. Methods We used a standard Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from http://www.clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)‐based oral PrEP safety in pregnant and breastfeeding HIV‐uninfected women. Results and discussion We identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP‐exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV‐uninfected women who use PrEP during pregnancy and/or lactation. Conclusions Expanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy.

Southern African guidelines on the safe, easy and effective use of pre-exposure prophylaxis: 2020

“… 2 , 3 , 4 , 5 Since then a further seven randomised controlled trials (RCTs) and numerous open label demonstration studies have led to the registration of combination therapy, with tenofovir and emtricitabine or related variations thereof as effective tools in the prevention of human immunodeficiency virus (HIV) transmission to uninfected persons. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 The World Health Organization (WHO) set a target of 3 million PrEP users worldwide by 2020. With 240 000 incident HIV infections per year in South Africa, which is equivalent to almost 15% of all new infections globally, 20 a significant portion of those effective PrEP users should be in this country.…”

Potential challenges to sustained viral load suppression in the HIV treatment programme in South Africa: a narrative overview

“…Prevention of mother-to-child transmission programmes have been highly successful; however, this has led to a certain extent of resistance in infants [ 30 ]. There is increasing exposure to antiretrovirals through pre-exposure and post-exposure prophylaxes in many African communities [ 31 ]. Antiretrovirals are also used in managing pathologies such as HBV [ 32 , 33 ]; and their use as narcotics has been reported [ 34 ].…”

Achievements and gaps to provide pre-exposure prophylaxis (PrEP) for women across the European Region – Results from a European survey study

“… 6 , 7 , 8 , 9 Current safety data also support the use of PrEP in pregnant and breastfeeding women. 10 , 11 Thus, PrEP offers women an efficacious, female-controlled HIV prevention choice. 12 …”