1. Understanding the Rationale of the 2015 WHO Guidelines on PrEP IAS Satellite Session Heather Watts M.D. Office of the Global AIDS Coordinator July 18, 2016

2. WHO 2016 Guidelines Language on PrEP and Pregnancy/Lactation Oral pre-exposure prophylaxis (PrEP) containing TDF should be offered as an additional prevention choice for people at substantial risk of HIV infection as part of combination HIV prevention approaches (strong recommendation, high-quality evidence). Pregnancy is associated with a higher risk of acquiring HIV, and HIV acquired during pregnancy or breastfeeding is associated with an increased risk of HIV transmission to the infant. In PrEP trials, exposure to TDF-containing PrEP during the first trimester of pregnancy was not associated with adverse pregnancy or infant outcomes. There is growing evidence of the safety of TDF and FTC + TDF during pregnancy and breastfeeding when used for treating maternal HIV or HBV (42)…. The risks and benefits of and alternatives to continuing to use PrEP during pregnancy and breastfeeding should be discussed with each person. Further research is needed to fully evaluate PrEP use during pregnancy and breastfeeding.

3. Risks of HIV in Pregnancy and Lactation Most studies show an increased risk of HIV acquisition during pregnancy and lactation compared to similar populations without pregnancy Risk may be 2-4 fold higher May be biological or related to partner behavior Risk of transmission high with acquisition during pregnancy or breastfeeding High viral load Infections often unrecognized and therefore untreated

4. What Data Are Available on TDF or TDF/XTC Use in Pregnancy and Lactation? Studies of TDF use for hepatitis B infection Included women with hepB DNA > 10 6-7 /copies/ml Exposure generally limited to second half of pregnancy Studies of women living with HIV receiving TDF/XTC as part of triple combination therapy during pregnancy and breastfeeding Women living with HIV have higher rates of adverse pregnancy outcomes with or without ART Additional drugs in regimen may contribute to observed effects Studies of women who conceive while receiving PrEP Exposure generally short-term b/o frequent pregnancy testing Low adherence in some studies limits conclusions regarding safety Tenofovir, rather than TDF, in breastmilk is poorly absorbed, limiting infant exposure tenofovir during breastfeeding.

5. TDF or TDF/XTC Outcomes No difference in maternal adverse events with or without TDF or TDF/XTD in hepatitis B+ or HIV+ women Pregnancy outcomes generally similar between TDF/XTC or no TDF/XTC Rates of conception Birth defects Stillbirth and other pregnancy loss Preterm birth and low birth weight Small for gestational age Infant growth Infant bone markers PROMISE study had increased preterm birth rate with lopinavir-based HAART compared to ZDV regardless of NRTI component. No difference in neonatal bone mineral content between TDF/FTC and ZDV/3TC HAART regimens in PROMISE.

6. WHO Deliberations Clear consensus for allowing PrEP use in pregnancy/breastfeeding Increased risk of acquisition Increased risk of transmission especially with unrecognized infection Large body of safety data based on use in HIV+ and hepatitis B+ women Threshold of substantial risk set at 3% for all Limited exposure to infant during breastfeeding As PrEP in women of childbearing age is implemented, it will be important to continue surveillance of maternal, pregnancy and infant outcomes to confirm the safety that reviews to date suggest.