1. Pregnancy & HIV/AIDS: Seeking Equitable Study Challenges to advancing HIV research in pregnancy: Insights from the HIV research community AIDS 2016 | Durban, South Africa | July 19, 2016 Sappho Gilbert*, Carleigh Krubiner, Kristen Sullivan Co-authors: Ruth Faden, Jean Cadigan, Margaret Little, Anne Lyerly, Leslie Meltzer Henry, Anna Mastroianni, Emily Namey

2. SETTING THE STAGE Pregnancy, HIV, research, & ethics

3. The problem 17.8 million women living with HIV around the world HIV leading cause of death among women of reproductive age 134 million births annually worldwide ~1.5 million HIV-infected women give birth worldwide each year Concerns about potential risks for pregnant women/fetuses  under-representation in clinical research Westreich et al. 2013 systematic review of 226 HIV-related studies: 81% do not mention pregnancy 15% include pregnant women

4. The problem Dearth of evidence to guide treatment of non-obstetrical illness during pregnancy Discrepancies in guidelines “Off label” dosing is commonplace

5. Pregnant women are different ↑ cardiac output, plasma volume ↓ gastric emptying, intestinal transport ↑ renal excretion ↕ drug metabolism ? vaginal absorption Altered HIV susceptibility Altered HIV transmission

6. Fear of fetal harm  reticence to include Failure to study may harm woman and fetus Harms of under-treatment may outweigh risks of medication use Efavirenz (EFV): first line ART in resource-limited settings Limited animal studies raised questions about teratogenicity Guidelines and tx algorithms contraindicated EFV in pregnancy Complicated delivery of treatment programs Potentially diverted pregnant women to ARVs that were less effective and potentially had more health risks In 2012, WHO revisited this issue and found no elevated risk of using EFV in pregnancy Guidelines updated to allow EFV use in pregnancy as first line

7. Research in pregnancy can be done! PMTCT reminds us this research is possible The early trials were not uncontroversial These studies were very successful, saved millions of lives Now a core part of our response to the epidemic Option B+ research in southern Africa

8. THE PHASES PROJECT Consultations with experts

9. PHASES Pregnancy & HIV/AIDS: Seeking Equitable Study Goal: to facilitate the ethically responsible inclusion of pregnant women and their health needs in HIV research Core Aims Identify scientific priorities in, perceived barriers and facilitators to, and novel research designs for research on HIV & pregnancy Develop an ethical framework for HIV research in pregnancy Generate and disseminate guidance recommendations

10. PHASES February–May 2014: spoke with 62 experts 6 group consultations at UNC, JHU, FHI 360 11 one-on-one conversations with investigators and clinicians Primarily US-based July 2015+: conducting more consultations Deep dives into South Africa, Botswana, & Malawi

11. FINDINGS TO DATE Priorities identified & barriers experienced

12. Research priority areas identified

13. Barriers experienced

15. NEXT STEPS Toward a road map

16. Conclusions Critical research gaps exist in HIV treatment and prevention in pregnancy Investigators experience numerous challenges to advancing this needed research Clearer guidance is needed to navigate the complex legal, regulatory, and ethical landscape This will enable the evidence-based advancement of women's health at the intersection of pregnancy & HIV

17. Refining & Dissemin- ating Refining & Dissemin- ating Project Overview Develop- ing Framework Fact-Finding Vetting HIV Investigators/Clinicians Legal & Regulatory Bodies Clinical Research Ethics Experts IRB Professionals Potential Research Participants

18. Ongoing work: mapping the road ahead

19. Thank you for your time, attention, & questions