SF City Clinic 2014 survey x HIV negative MSM population of 50,000;. 2. SF NHBS self report of STI among MSM with 0 ncAI in 2014 x HIV negative MSM population of 50,000;. 3. SF NHBS MSM reporting female partners in 2014 x HIV positive MSM population of 14638. 4. IDU and ncRAI in est. 923 HIV negative trans ...
ORAL PRE-EXPOSURE PROPHYLAXIS STATE OF THE ART Stefan Baral
Outline
Topical/Oral PrEP Studies Overview Determinants of PrEP Initiation and Adherence Ongoing PrEP Studies
Oral/Topical PrEP Efficacy/Effectiveness
Modified: Abdool Karim et al, AVAC Report, 2014
PrEP works, but adherence is key
“Forgiveness” TFV Concentration: Rectal>Cervical>Vaginal
Days post single-dose Patterson KB et al. Sci Transl Med. 2011.
IPrEx : Correlates of Prep protection
Source: Grant et al, Lancet ID, 2014
iPrEx OLE (Open Label Extension) San Francisco Data
12 Months
81% still on PrEP 92% of whom use 4+ tablets per week
Source: Grant Lancet ID 2014 14(9):820-9; Estimated from dried blood spots in iPrEx OLE in San Francisco. Grant CROI Abstract 25 Seattle 2015.
Ipergay – Placebo-Controlled
Credit: Molina JM, CROI 2015
Ipergay Results Significantly fewer new HIV infections with intermittent PrEP versus placebo (2 versus 14 cases)
86% reduction after a mean follow-up of 13 months (P=0.002)
Safety of on-demand PrEP was similar to placebo except for GI adverse events Adherence to PrEP was good, supporting the acceptability of on-demand PrE Pts averaged 16 pills/mo
Molina JM, et al. 22nd CROI. Seattle, 2015. Abstract 23LB.
HIV Incidence
HIV Incidence (per 100-person-years)
6.6 86% Reduction (P=0.002)
0.94
Placebo
Intermittent PrEP
PROUD Individual RCT
A multi-centre, open label randomised design to immediate or deferred inclusion of PrEP as part of the package of HIV risk reduction interventions. Setting: STI Clinics Intervention: HIV testing, Dx/Tx of STI, Condoms, PEP
Main Outcome
+/- Truvada PrEP Time to Accrual of 500 Participants Retention at 12/24 Months
Secondary Outcome
HIV Incidence over a 12 month period (powered on this) Renal function, HIV resistance among men who acquire HIV, Adherence, Risk Compensation, Facilitators/Barriers to Adherence
http://www.proud.mrc.ac.uk/pdf/PROUD_protocol%20v1%203%2014October2014.pdf
PROUD Results
Credit: McCormack S, CROI 2015
PrEP Demo Project Sites (Liu and Cohen) San Francisco City Clinic (N=300)
Miami-Dade County Downtown STD clinic (N=157)
Whitman Walker Health (N=100)
• Annual HIV seroconversion rate among MSM >2% across clinics • Participants were either clinic referred (46%) or self-referred (54%) Modified from: Mayer et al. 2015
PrEP Demo Results: Adherence 100%
Protective TFV-DP in DBS
90%
Rating scale: very good/excellent
80% 70%
Medication Possession Ratio (mean)
Percent
60% 50%
• 63% had protective DBS levels at all visits • 3% always had DBS levels 4 pills/week TDF levels not linked to behavioral risk
Truvada Adherence
iPrex (TW only)
18%
FEM-PrEP
24%
VOICE
29%
Hormone use associated with lower detection of TDF Adherence? Interactions?
Deutsch 2015
New technologies and PrEP adherence ↑ treatment adherence with text messaging Wisepill: used in Life-Steps HAART adherence intervention modified for PrEP, including daily SMS with pts →84% drug levels c/w daily use at 6 months Electronic diaries studied in SF and Chicago was associated with ↑ adherence SexPro App with diary features and adherence support, tested in NYC, SF, Lima and Rio De Janeiro Feedback on drug levels been studied as adjunct to counseling 25
Source: Buchbinder, Amico/Hosek, Mayer/Safren, Landovitz, Lester,
HealthMindr App: A comprehensive HIV Prevention Resource for US MSM
Source: Sullivan, 2016
HealthMindr Pilot Study Participants
Recruitment Strategy
121 MSM enrolled
72 in Atlanta, GA 49 in Seattle, WA
18+ years Never tested HIV positive Only available to Android users
Source: Sullivan, 2016
Facebook banner ads Grindr mass text messages & banner ads 4 month study Recruited from May-Aug Finish followup in December
84 have completed Final Evaluation
App Pages Accessed by Users
Source: Sullivan, 2016
PrEP starts: HealthMindr Pilot
7/70 PrEP eligible started PrEP “I went through and put in my (screener) responses and it basically said ‘Hey maybe you should check out PrEP as an option and by the way here are some places you could go.’ … I was seen (for PreP) at [provider] within a week … Easy breezy. (Healthmindr) was the piece that crossed the threshold from inaction to actual action. … This (Healthmindr) will saves lives, and I can even say maybe my life.” Pilot participant
Source: Sullivan, 2016
PrEP at Home: Reducing Monitoring Burden
CDC Guidance for PrEP calls for repeat HIV testing every three months, repeat STI testing at every 6 months, and ongoing PrEP adherence counseling. 879,000 – 1,696,000 US MSM would be behaviorally eligible for PrEP (100,000 Canadians?) With recommended quarterly visits,
3,518,000 - 6,785,000 patient visits per year would be required for clinic-based HIV, STI and creatinine testing
A home care kit could alleviate the economic burden on patients, providers and the healthcare system Source: Sullivan, 2016
Adherence Support
Source: Ayogo, 2016
Gamification App
Source: Ayogo, 2016
CABOTEGRAVIR: GSK126744 Long Acting II
Favorable attributes for PrEP: • High genetic barrier to resistance • PK profile – half life of 21-50 days -allows once-daily oral or 1-3 month injectable dosing using nanosuspension formulation
Muller et al, European Journal of Pharmaceutics and Biopharaceutics,2011 Spreen, 7th IAS, 2013; Min, ICAAC, 2009 Taoda, International Congress on Drug Therapy in HIV Infection, 2012
HPTN 083 A Phase 2b/3 Double Blind Safety and Efficacy Study Of Quarterly Injectable Cabotegravir Compared to Daily Oral TDF/FTC, For Pre-Exposure Prophylaxis in HIV-Uninfected Men and Transgender Women who have Sex With Men
• • •
N = 4500 Study duration: Up to 4.5 years Sites pending (Americas; Asia; very limited in Africa)
Arm A
Arm B
Step 1
Daily oral CAB and oral TDF/FTC placebo
Daily oral TDF/FTC and oral CAB placebo
Step 2
Injectable CAB every 12 weeks and daily oral TDF/FTC placebo
Daily oral TDF/FTC and injectable placebo every 12 weeks
Step 3
Open-label daily oral TDF/FTC to cover the PK tail, for up to 48 weeks
Transition to locally-available HIV prevention services
Summary
Oral PrEP theoretically can achieve close to 100% effectiveness in men with sufficient adherence Body of work to date has been about efficacy and linkage Ongoing work is focused on
Specific populations
Adherence
Minority and Young MSM Male Sex Workers (ie occupational PrEP) Transgender Women Focus on looking past SMS reminders and leveraging new technologies…
New PrEP Agents
TAF Maraviroc Long Acting Integrase Inhibitors (nanosuspensions, implants)
Acknowledgements
Ken Mayer Patrick Sullivan Chris Beyrer Tonia Poteat Mike Cohen Key Populations Program
Carrie Lyons, Ashley Grosso, Sosthenes Ketende, Ben Liestman, Sheree Schwartz, Gnilane Turpin Nunez, Karleen Coly, Iliassou Mfochive Njindam, Clarence Yah, Shauna Stahlman
