PrEP has high efficacy for HIV-1 prevention among higher-risk HIV-1 serodiscordant couples: a subgroup analysis from the Partners PrEP Study Erin Kahle 1 , Deborah Donnell 2 , James Hughes 1 , Katherine Thomas 1 , Grace John-Stewart 1 , Edith Nakku-Joloba 3 , Elizabeth Bukusi 4 , Jairam Lingappa 1 , Connie Celum 1 , Jared Baeten 1 for the Partners PrEP Study Team 1 University of Washington, Seattle, WA, USA; 2 Fred Hutchinson Cancer Research Center, Seattle,WA, USA; 3 Makerere University, Kampala, Uganda; 4 Kenya Medical Research Institute, Nairobi, Kenya;
Transcript
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, Jairam Lingappa1,
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;
PrEP
Pre-exposure prophylaxis (PrEP) is effective in reducing HIV-1 acquisition in multiple populations
1° endpoint: HIV infection in HIV- partnerCo- 1° endpoint: Safety
Follow couples for up to 36 months
FTC/TDF once daily
Partners PrEP Study Sites
KenyaEldoret, Kisumu,NairobiThika
UgandaJinja,Kabwohe Kampala,Mbale,Tororo
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)
Risk score worksheet
Kahle CROI 2012
Risk score worksheet
Kahle CROI 2012
Risk score worksheet
Kahle CROI 2012
Risk score = 7
HIV-1 incidence by risk score- PrEP placebo arm
HIV-1 incidence by risk score- PrEP placebo arm
High risk subgroup
• Comparable incidence to FemPrEP (5/100) and VOICE (6/100)
High risk couples subgroup
4758 PrEP couples
1087 higher risk couples
(risk score ≥6)
346 TDF 354 FTC/TDF 380 placebo
High risk couples (risk score ≥6)Risk score characteristics High risk group,
N=1087Full cohort,
N=4503 Age 29 (24-35) 33 (28-40)
Number of children 1 (0-2) 2 (1-4)
Male HIV-1 uninfected partner uncircumcised 874 (80.4%) 1312 (29.1%)
Unprotected sex within partnership, prior 30 days
678 (62.4%) 1245 (27.8%)
HIV-1 plasma viral load, HIV-1 infected partner
50,000 copies/mL or higher 560 (51.5%) 804 (17.8%)
10,000-49,999 copies/mL 295 (27.1%) 1237 (27.5%)
Less than 10,000 copies/mL 232 (21.3%) 2462 (54.7%)
HIV-1 incidence, per 100 person-years 0.65 0.50 1.99
HIV-1 protection efficacy, vs. placebo (95%CI) 67% (44-81%)
75% (55-87%)
p-value <0.001 <0.001
High risk subgroup analysis mITT TDF FTC/TDF Placebo
Number of HIV-1 infections 7 6 28
HIV-1 incidence, per 100 person-years 1.34 1.10 5.01
HIV-1 protection efficacy, vs. placebo (95%CI) 72% (35-88%)
78% (46-91%)
p-value 0.001 <0.001
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
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
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, Namandjé Bumpus
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
