Adherence and Acceptability for PrEP formulations Jessica Haberer, MD, MS July 24, 2017

Conflicts of Interest I have no conflicts to declare Grant funding: US National Institutes of Health, Bill and Melinda Gates Foundation, USAID Consultation: US National Institutes of Health, World Health Organization, Merck Stock: Natera

Overview Factors influencing adherence and acceptability Multi-purpose technologies Prevention-effective adherence Perspective on adherence and effectiveness Conclusions

Factors influencing prevention adherence (Bekker, Lancet, 2015)

Adherence factors by PrEP formulation Dosing Daily Periodic On demand Product formulations Oral tablets Vaginal or rectal microbicide Vaginal rings Depot injections Unique adherence facilitators Pair with daily routine (habit formation) Infrequent dosing Not a part of daily life Less susceptible to stigma Dosing only on cue (sex) Unique adherence barriers Fatigue More susceptible to stigma Remembering infrequent dosing Discomfort (physical or psychological) Being prepared for cue

Factors influencing acceptability (Tolley, Antivir Res, 2013)

Choice is important for acceptability Satellite sessions: Next Wave of Prevention Options (AVAC) Making Strides with Systemic PrEP (Hall, JMIR, 2016)

Multi-purpose technologies HIV prevention alone may not be a top priority Motivation for adherence may increase with combined PrEP, contraception and/or prevention for other sexually transmitted infections (e.g., acyclovir for HSV) Rings Oral tablets Depot Injections Vaginal tablets (Malcolm, BJOG, 2014; Boyd, Intl J Pharm, 2016; McConville, Eur J Pharm Biopharm, 2016)

Prevention-effective adherence Prevention-effective adherence: alignment of adherence and risk for HIV acquisition (Haberer, AIDS, 2015) PrEP use in this way can be high efficient: protection when needed with minimal individual burden and cost

Prevention-effective adherence Requires knowledge of risk for HIV acquisition Daily and periodic dosing should be assessed as “seasons” On demand dosing needs on-going assessment; risk for inaccurate assessment mitigated through user friendly tools (e.g., Play Sure Kit) All methods require good counseling and attention to acceptability NYC Play Sure Kit

Perspective on adherence in prevention Oral PrEP Study Adherence Efficacy 2010 iPrEx 51% (plasma TFV) 44% 2012 Partners PrEP 82% (plasma TFV) 75% 2016 PROUD Partners Demo Project 86% (days covered) 86% (plasma TFV) 86% 96% Relevant factors Clinical trial experience Knowledge of efficacy Self-selection/acceptability Vaginal ring 2015 ASPIRE The Ring Study 82% (plasma DPV ) 84% (plasma DPV) 27% 31% anticipated HOPE, DREAM ? (Grant, NEJM, 2010; Baeten, NEJM, 2012; McCormick, Lancet, 2016; Baeten, NEJM, 2017; Nel, NEJM 2017; Brown, IAS 2016 )

Perspective on adherence in prevention Oral PrEP Study Adherence Efficacy 2010 iPrEx 51% (plasma TFV) 44% 2012 Partners PrEP 82% (plasma TFV) 75% 2016 PROUD Partners Demo Project 86% (days covered) 86% (plasma TFV) 86% 96% Relevant factors Clinical trial experience Knowledge of efficacy Self-selection/acceptability Vaginal ring 2015 ASPIRE The Ring Study 27-42% (residual ring DPV ) 84% (plasma DPV) 65% 31% anticipated HOPE, DREAM ? (Grant, NEJM, 2010; Baeten, NEJM, 2012; McCormick, Lancet, 2016; Baeten, NEJM, 2017; Nel, NEJM 2017; Brown, IAS 2016 )

Adherence and preferences “…a less efficacious barrier (one that fails more often than another on each sexual encounter), if frequently used, might serve the public health as well or better than a more efficacious but less frequently used barrier, and could in the end play an important role in preventing transmission at the population level.” (Am J Pub Health, 1990)

Conclusions Adherence and acceptability are multi-faceted Choice matters and one size will not fit all Multi-purpose technologies may increase acceptability and adherence Prevention-effective adherence is the goal Adherence evolves over time as experience with each PrEP product increases