Safety Review of Tenofovir Disoproxil Fumarate/Emtricitabine PrEP for Pregnant Women

Front view close up of a nude pregnant belly with ray of light.
A safety review evaluated several studies assessing the safety of PrEP in pregnant women, including the Partners PrEP Study, TDF2 Study, FEM-PrEP, and VOICE.

“The data collected to date on tenofovir disoproxil fumarate (TDF)-based HIV pre-exposure prophylaxis (PrEP) use during pregnancy are reassuring, indicating that the frequency of adverse pregnancy, birth, and infant growth outcomes among mothers and infants exposed to TDF-based PrEP in pregnancy is no more common than that experienced by mothers or infants without TDF exposure,” according to findings of a safety review published in Expert Opinion on Drug Safety.

Authors reviewed several studies that evaluated the safety of PrEP in pregnant women, including the Partners PrEP Study, TDF2 Study, FEM-PrEP, and VOICE. In all 4 trials, investigators found that the frequency of adverse pregnancy outcomes did not differ significantly between the active PrEP regimen and the placebo arms. In the FEM-PrEP study, complete data were not reported on pregnancy complications, but it was noted that vaginal bleeding was the most common complication. In the VOICE study, subsequent follow-up showed no difference between the PrEP and placebo arms in growth indicators in the first year of life in infants born to enrolled mothers.

Studies with pregnant women living with HIV had different findings than previously mentioned. A meta-analysis observed significantly lower rates of preterm delivery and stillbirth among women who received TDF-based antiretroviral therapy compared with women who did not receive TDF-based regimens. However, the PROMISE trial showed that women who received TDF-based therapy were more likely to have preterm delivery and neonatal mortality compared with women who received zidovudine-based therapy but not when compared with women using zidovudine alone. Another study showed that adjusted mean length-for-age and head circumference z-scores at 1 year of age were smaller among children whose mothers used TDF-based therapy during pregnancy.

The following are potential alternative PrEP therapies for pregnant women: tenofovir alafenamide with emtricitabine; dapivirine vaginal ring; and cabotegravir injectable.

“While current data are reassuring on safety in pregnancy, additional robust data from prospective studies and implementation projects that actively recruit women prior to conception or during pregnancy are still essential to better understand the pharmacokinetics, safety, and efficacy of TDF-based PrEP in pregnancy,” study authors concluded.


Stalter RM, Pintye J, Mugwanya KK. Safety review of tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis for pregnant women at risk of HIV infection. Expert Opin Drug Saf. Published online May 28, 2021. doi:10.1080/14740338.2021.1931680