PrEP

1. PrEP has high efficacy for HIV-1 prevention among higher-risk HIV-1 serodiscordant couples: a subgroup analysis from the Partners PrEP Study Erin Kahle1, Deborah Donnell2, James Hughes1, Katherine Thomas1, Grace John-Stewart1, Edith Nakku-Joloba3, Elizabeth Bukusi4, JairamLingappa1, Connie Celum1, Jared Baeten1 for the Partners PrEP Study Team 1University of Washington, Seattle, WA, USA; 2Fred Hutchinson Cancer Research Center, Seattle,WA, USA; 3Makerere University, Kampala, Uganda; 4Kenya Medical Research Institute, Nairobi, Kenya;

2. PrEP Pre-exposure prophylaxis (PrEP) is effective in reducing HIV-1 acquisition in multiple populations AP/Paul Sakuma

3. Oral PrEP efficacy trial results

4. Oral PrEP efficacy trial results

5. Oral PrEP efficacy trial results

6. PrEP in serodiscordant couples • Serodiscordant couples are common and contribute a high proportion of new HIV-1 cases in sub-Saharan Africa • HIV acquisition risk is high for uninfected partners in discordant relationships but level of risk varies between couples • Limited data on PrEP efficacy in highest risk serodiscordant couples

7. Objectives Identify and assess efficacy of PrEP among a subgroup of higher-risk heterosexual HIV-1 serodiscordant couples from the Partners PrEP Study

8. 4758 HIV serodiscordant couples (HIV+ partner not yet medically eligible for ART) Randomize HIV- partners (normal liver, renal, hematologic function) TDF once daily FTC/TDF once daily Placebo once daily Follow couples for up to 36 months 1° endpoint: HIV infection in HIV- partner Co- 1° endpoint: Safety Partners PrEP study design

9. Kenya Eldoret, Kisumu, Nairobi Thika Partners PrEP Study Sites Uganda Jinja, Kabwohe Kampala, Mbale, Tororo

10. HIV-1 risk score for serodiscordant couples We developed a novel risk scoring tool, made up of a discrete combination of baseline clinical and behavioral factors, that would define HIV-1 transmission risk (Kahle, CROI 2012 Abstract 1102)

11. Risk score worksheet Kahle CROI 2012

12. Risk score worksheet Kahle CROI 2012

13. Risk score worksheet Risk score = 7 Kahle CROI 2012

14. HIV-1 incidence by risk score- PrEP placebo arm

15. HIV-1 incidence by risk score- PrEP placebo arm High risk subgroup • Comparable incidence to FemPrEP (5/100) and VOICE (6/100)

16. High risk couples subgroup 4758 PrEP couples 1087 higher risk couples (risk score ≥6) 354 FTC/TDF 346 TDF 380 placebo

17. High risk couples (risk score ≥6)

18. PrEP efficacy results

19. PrEP efficacy results

20. PrEP efficacy results

21. PrEP efficacy results

22. PrEP efficacy results

23. PrEP efficacy results

24. PrEP efficacy results

25. Summary • A high risk subgroup of heterosexual HIV-1 serodiscordant couples can be identified using a composite risk scoring tool, and • HIV-1 incidence is significantly higher in that high risk subgroup of HIV-1 serodiscordant couples, but • Oral PrEP provides substantial protection against HIV-1 acquisition in higher risk serodiscordant couples, comparable to that seen in all couples in the Partners PrEP Study

26. Conclusion • Although Fem-PrEP and VOICE had a higher incidence, reflecting a higher risk population, our data do not support the hypothesis that the futility of PrEP in those studies was a result of higher HIV-1 transmission risk • Ongoing demonstration projects of PrEP that target the highest risk populations will maximize the potential to reduce HIV-1 transmissions

27. Acknowledgements • Study participants and staff • Funding: Bill and Melinda Gates Foundation and NIH/NIMH R01 MH095507 • Partners PrEP Study Team • Sites: • Eldoret, Kenya (Moi U, Indiana U): Edwin Were (PI), Ken Fife (PI), Cosmas Apaka • Jinja, Uganda (Makarere U, UW); Patrick Ndase (PI), Elly Katabira (PI), Fridah Gabona • Kabwohe, Uganda (KCRC): Elioda Tumwesigye (PI), Rogers Twesigye • Kampala, Uganda (Makarere U): Elly Katabira (PI), Allan Ronald (PI), Edith Nakku-Joloba • Kisumu, Kenya (KEMRI, UCSF): Elizabeth Bukusi (PI), Craig Cohen (PI), Josephine Odoyo • Mbale, Uganda (TASO, CDC): Jonathan Wangisi (PI), Akasiima Mucunguzi • Nairobi, Kenya (KNH/U Nairobi, UW): James Kiarie (PI), Carey Farquhar (PI), Grace John-Stewart (PI), Harrison Tamooh • Thika, Kenya (KNH/U Nairobi, UW): Nelly Mugo (PI), Kenneth Ngure • Tororo, Uganda (CDC, TASO): Jim Campbell (PI), Jordan Tappero (PI), Aloysious Kakia • University of Washington Coordinating Center: • Connie Celum (PI and Co-Chair), Jared Baeten (Co-Chair and Medical Director), Deborah Donnell (Statistician), Justin Brantley, Tami Cloutier, Robert Coombs, Amy Dao, Shauna Durbin, Mira Emmanuel-Ogier, Lisa Frenkel, Carlos Flores, Harald Haugen, Renee Heffron, Ting Hong, Jim Hughes, Erin Kahle, Johanna Karas, Becky Karschney, Lara Kidoguchi, Meighan Krows, Matt Leidholm, Jai Lingappa, Toni Maddox, Angela McKay, Julie McElrath, Allison Mobley, Susan Morrison, Nelly Mugo, Andrew Mujugira, Vikram Nayani, Patrick Ndase, Apollo Odika, Hilda O’Hara, Dana Panteleeff, Jennifer Revall, Marothodi Semenya, John Sparkman, Kathy Thomas, Ellen Wilcox • Adherence Ancillary Study: David Bangsberg, Jessica Haberer, Norma Ware, Monique Wyatt, Steve Safren, Christina Psaros, Craig Hendrix, NamandjéBumpus • DF/Net (data center): Lisa Ondrejcek, Darryl Pahl, Jae Chong • CLS (laboratory oversight): Wendy Stevens, Charlotte Ingram, Ute Jentsch, Mukthar Kader, Nombulelo Gqomane, Feroza Bulbulia, Jan van den Heuvel • ClinPhone/Perceptive Informatics (randomization)