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?

Dvora L Joseph Davey^{1

2}, Jillian Pintye³, Jared M Baeten^{3

4

5}, Grace Aldrovandi⁶, Rachel Baggaley⁷, Linda-Gail Bekker⁸, Connie Celum³, Benjamin H Chi⁹, Thomas J Coates⁶, Jessica E Haberer¹⁰, Renee Heffron^{3

4}, John Kinuthia^{3

11}, Lynn T Matthews¹², James McIntyre^{2

13}, Dhayendre Moodley^{14

15}, Lynne M Mofenson¹⁶, Nelly Mugo^{3

17}, Landon Myer², Andrew Mujugira^{3

18}, Steven Shoptaw^{6

19}, Lynda Stranix-Chibanda²⁰, Grace John-Stewart^{3

4}; PrEP in Pregnancy Working Group

Affiliations

¹ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
² Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
³ Department of Global Health, University of Washington, Seattle, WA, USA.
⁴ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁵ Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Geffen School of Medicine, University of California, Los Angeles, CA, USA.
⁷ World Health Organization, Geneva, Switzerland.
⁸ Faculty of Health Sciences, Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, NC, South Africa.
⁹ Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁰ Center for Global Health, Massachusetts General Hospital, Boston, MA, USA.
¹¹ Department of Research and Programs, Kenyatta National Hospital, Nairobi, Kenya.
¹² Department of Medicine, University of Alabama, Birmingham, AL, USA.
¹³ ANOVA, Johannesburg, South Africa.
¹⁴ Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, Durban, South Africa.
¹⁵ Centre for AIDS Research in South Africa, Durban, South Africa.
¹⁶ Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA.
¹⁷ Center for Clinical Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
¹⁸ Infectious Diseases Institute, Makerere University, Kampala, Uganda.
¹⁹ Department of Family Medicine, University of California, Los Angeles, CA, USA.
²⁰ University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.

PMID: 31912985
PMCID: PMC6948023
DOI: 10.1002/jia2.25426

Meta-Analysis

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?

Dvora L Joseph Davey et al. J Int AIDS Soc. 2020 Jan.

. 2020 Jan;23(1):e25426.

doi: 10.1002/jia2.25426.

Authors

Affiliations

¹ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
² Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
³ Department of Global Health, University of Washington, Seattle, WA, USA.
⁴ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁵ Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Geffen School of Medicine, University of California, Los Angeles, CA, USA.
⁷ World Health Organization, Geneva, Switzerland.
⁸ Faculty of Health Sciences, Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, NC, South Africa.
⁹ Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁰ Center for Global Health, Massachusetts General Hospital, Boston, MA, USA.
¹¹ Department of Research and Programs, Kenyatta National Hospital, Nairobi, Kenya.
¹² Department of Medicine, University of Alabama, Birmingham, AL, USA.
¹³ ANOVA, Johannesburg, South Africa.
¹⁴ Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, Durban, South Africa.
¹⁵ Centre for AIDS Research in South Africa, Durban, South Africa.
¹⁶ Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA.
¹⁷ Center for Clinical Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
¹⁸ Infectious Diseases Institute, Makerere University, Kampala, Uganda.
¹⁹ Department of Family Medicine, University of California, Los Angeles, CA, USA.
²⁰ University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.

PMID: 31912985
PMCID: PMC6948023
DOI: 10.1002/jia2.25426

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 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.

Keywords: HIV; PMTCT; PrEP; breastfeeding; preexposure prophylaxis; pregnancy; prevention of mother to child transmission.

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Figures

**Figure 1**
PRISMA flow chart of identified studies and projects on maternal and infant outcomes following oral PrEP exposure during pregnancy and breastfeeding (10 to 30 March 2019).

**Figure 2**
(a) Timing of teratogenic exposures during pregnancy and adverse potential outcomes 64. (b) Time and duration of pre/postnatal PrEP exposure in completed (light grey) and ongoing/planned studies (dark grey).

See this image and copyright information in PMC

References

1. Drake AL, Wagner A, Richardson B, John‐Stewart G. Incident HIV during pregnancy and postpartum and risk of mother‐to‐child HIV transmission: a systematic review and meta‐analysis. PLoS Med. 2014;11:e1001608. - PMC - PubMed
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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?

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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?

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