1. What is known about the safety of PrEP in pregnancy? Lynda Stranix-Chibanda

2. 2 ARV use in pregnant women Cornerstone of highly successful PMTCT programme Clear benefit apparent for woman and infant – Small but significant risk of adverse effects are offset by the significant health benefits – Category B agents As more women begin PrEP, risk-benefit ratio in the HIV-uninfected population requires evaluation

3. 3 Data from other populations? Studies in men or non-pregnant women may not translate directly into the pregnant and postpartum context This is most obvious with regard to foetal / infant development, but a better understanding of obstetrical outcomes with PrEP is also urgently needed

4. 4 Pregnancy Considerations Important safety issues to consider for PrEP use in pregnant and lactating women – Early pregnancy – time of organogenesis – foetal malformations foetal loss – Later pregnancy – physiological changes – hepatotoxicity risk, plasma drug levels foetal growth – intrauterine growth restriction ARV effects on organ function – maternal bone density, renal and hepatic function

5. 5 Pregnancy Considerations Important safety issues to consider for PrEP use in pregnant and lactating women – Perinatal – infant prematurity still birth low birth weight low bone mineral content neonatal death infant anaemia lactic acidosis

6. 6 PrEP Pipeline Large number of ARV preparations in the PrEP pipeline Different drugs and different delivery systems The amount of human safety data available increases as a product progresses through the pipeline Safety data in pregnancy may not be a priority for drug manufacturers until a product has shown promising results in phase II or III trials – and then we begin with trials in pregnant non-human primates

7. 7

8. 8 Truvada We have PK and safety in HIV+ pregnant women from PMTCT programmes globally – Renal function and bone health Safety data in HIV-negative / Hepatitis B + PrEP implementation programmes – Sero-discordant couples initiating ART/PrEP – Planned conception (PrEPception) – VOICE trial oral arm – Pregnancy registries Opportunistic data

9. 9 Other PrEP ARVs Varying levels of opportunistic data – Early phase trials specifically designed to exclude pregnant women, require use of contraceptives and stop product use when pregnancy is confirmed (foetal exposure for usually less than 6 weeks) Capacity to design, approve and implement research of novel products in pregnancy

10. 10 What are the gaps? – Do pregnant women perceive the HIV risk? – Do they accept PrEP as a prevention option? – When will they take it? What helps adherence? – Is there potential negative stigma related to PrEP use? – Is PrEP safe for mothers/infants to use? – Is the PrEP dose correct? – Does PrEP work? – Is PrEP in this population cost effective? [poster presentation Wednesday and JAIDS Supplement August 2016, Joni Price] IMPAACT 2009

11. 11 What do we know? Truvada – quite a lot, not all is relevant to the pregnant woman – Individual women make an informed choice about using PrEP in pregnancy Other ARVs – very little

12. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. 12 Sharon Hillier, Heather Watts and satellite organisers IMPAACT, Sharon Nachman, James McIntyre IMPAACT 2009 protocol team Ben Chi and Sybil Hosek UZ-UCSF and UZ-CHS Mike Chirenje, Tsungai Chipato and Nyaradzo Mgodi Lynne Mofenson Acknowledgements