An international study, led by a University of KwaZulu-Natal professor, has confirmed the safe use of tenofovir disoproxil fumarate/emtricitabine as a pre-exposure prophylaxis (PrEP) in pregnant HIV-negative women.
Despite a 2018 study finding that women were nearly three times more likely to become infected with HIV during pregnancy and four times as likely six months’ post-partum, compared with the risk of HIV infection at other times, until 2019, pregnant and lactating women in SA did not receive the PrEP roll-out due to a lack of safety data on its use in pregnancy.
Unprotected sex and hormonal changes, among other factors, expose pregnant women to a higher risk of HIV infection.
The novel study, published in The Lancet HIV, and led by University of KwaZulu-Natal Professor Dhayendre Moodley, is a pioneering approach providing much needed safety data to allow for a more informed choice during pregnancy to protect mother and baby from the long-term effects of HIV.
The research – funded by Gilead Sciences and the South African Medical Research Council, with participation from global scientists – examined the impact of the treatment on pregnant women.
The findings suggest that “initiation of tenofovir disoproxil fumarate and emtricitabine PrEP in pregnancy does not increase the occurrence of preterm birth, small for gestational age, or any adverse pregnancy outcome”.
“Moreover,” the researchers said, “this study is likely to be the last clinical trial comparing PrEP with no PrEP, and provides a valuable benchmark for adverse pregnancy outcomes for future planned studies of novel PrEP strategies.”
“HIV and Aids remain significant problems in South Africa, where women continue to bear a disproportionate burden of HIV. We need to double down on interventions that can work. PrEP in pregnancy is the first step in preventing HIV in women and critical in our battle to eradicate HIV in children,” said the SAMRC president and CEO Professor Glenda Gray, one of the experts involved in the study.
Study details
Pregnancy and neonatal safety outcomes of timing of initiation of daily oral tenofovir disoproxil fumarate and emtricitabine pre-exposure prophylaxis for HIV prevention (CAP016): an open-label, randomised, non-inferiority trial
Dhayendre Moodley, Carl Lombard, Vani Govender, Megeshinee Naidoo, Alicia Desmond, Kimesh Naidoo, et al.
Published in The Lancet HIV on 3 February 2023
Summary
Background
The safety of tenofovir disoproxil fumarate and emtricitabine as pre-exposure prophylaxis (PrEP) in pregnant women not living with HIV is uncertain. We aimed to compare pregnancy and neonatal outcomes in women exposed and not exposed to PrEP during pregnancy.
Methods
In this single-site, open-label, randomised, non-inferiority trial in Durban, South Africa, we evaluated pregnancy and neonatal outcomes in pregnant women aged 18 years or older, not living with HIV, and at 14–28 weeks' gestation at the time of enrolment. Eligible participants were randomly assigned (1:1) using a computer-generated permuted block (block size of ten) randomisation list to immediate initiation or deferred initiation of PrEP until breastfeeding cessation. Participants in the immediate PrEP group received a monthly supply of once daily oral tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg. Participants in the deferred PrEP group received standard of care for HIV prevention. The primary outcomes were the occurrence of preterm live birth (<37 weeks gestational age) and very preterm birth (<34 weeks gestational age) determined by menstrual dating, low birthweight (<2500 g), very low birthweight (<1500 g), stillbirth (≥20 weeks gestational age), and small for gestational age (birthweight less than the tenth percentile). Post-natal safety outcomes will be reported elsewhere. We used binomial regression models to estimate risk differences and two-sided 90% CIs. Immediate PrEP was non-inferior to deferred PrEP if the upper bound of the 90% CI of the risk difference was less than the upper predefined non-inferiority margin for preterm birth (7·5%), very preterm birth (2·6%), low birthweight (5·5%), very low birthweight (1·2%), stillbirth (1·0%), and small for gestational age (3·7%). All outcomes were analysed in the intention-to-treat population.
Findings
Between Sept 25, 2017, and Dec 6, 2019, we screened 693 women, of whom 540 were randomly assigned to immediate PrEP (n=271) or deferred PrEP (n=269). The median gestational age was 19 weeks (IQR 15–23 for immediate PrEP and 16–23 for deferred PrEP). The risk difference between the immediate PrEP group and the deferred PrEP group for preterm birth was –4·7% (90% CI –10·7 to 1·2; immediate PrEP was non-inferior), for very preterm birth was 0·6% (–3·4 to 4·6; upper limit exceeded the non-inferiority margin), for low birthweight was 2·5% (–1·6 to 6·6; upper limit exceeded the non-inferiority margin), for very low birthweight was 0% (–1·4 to 1·4; upper limit exceeded the non-inferiority margin), for stillbirth was 1·2% (–1·5 to 3·8; upper limit exceeded the non-inferiority margin), and for small for gestational age was 0·9% (–1·2 to 2·9; immediate PrEP was non-inferior).
Interpretation
In our study, PrEP was not associated with preterm birth or small for gestational age infants. Our data support the use of tenofovir disoproxil fumarate and emtricitabine in pregnancy and our reassuring findings can be used to allay safety concerns among pregnant women.
See more from MedicalBrief archives:
Trial stopped: Long-acting injectable highly effective in preventing HIV in women
Preventive drug regimen in at-risk group increases PrEP uptake — Eswatini
Questions over PrEP safety during pregnancy should not prevent treatment
Women with limited power over decisions could benefit from PrEP