José Bauermeister PhD, MPH University of Pennsylvania MTN BRWG Member

Anal Sex and “Risk” in a PrEP era In a PrEP/TasP era, how do we expand our conversations regarding anal sex in the lives of all communities? How can we celebrate PLEASURE, INTIMACY, CONNETION & EMOTION?

Flipping the script… Traditional Research Awareness Tolerability Acceptability Adherence Sustainability Design-driven Research How can we understand participants’ contexts better? How do we get them to desire our product? What makes people keep wanting to use our product? How do we make a product that is easy and vital to way of life?

Choice matters… Planning and discussing condoms (and lube) for anal sex can be difficult. Oral PrEP may not be accessible, available or desired among population segments. Access & Cost Adherence Challenges Access to continued care Change in insurance Changes in perceived risk Perceived side-effects Self-management difficulties Stigma Topical prophylaxis (e.g., microbicides) may be desired among vulnerable populations who experience risk seasonally.

Microbicides are compounds that could be applied inside the vagina or rectum and could eliminate, or at least significantly decrease, the chances of HIV transmission provided that people are able and willing to use them (“acceptability”) correctly & consistently (“adherence”).

Topical or Event-Driven Formulations Rectal microbicide products (e.g., gels, inserts, enemas) may have biological and behavioral advantages over oral PrEP and/or alternative systemic approaches. May be able to achieve high drug concentrations in local tissue and potential toxicities and resistance linked to systemic exposure. May be linked to behaviors (use of lube, douching) that people already engage in around anal sex. Adherence to dosing, daily or long-lasting, will be complicated due to accessibility and availability, particularly among the most disadvantaged or marginalized. Current Rectal Microbicide Agenda Behaviorally Congruent Gel: MTN-026/MTN-033 MPT Gel: MTN-037 (HIV-1, herpes simplex virus type 2, and HPV). Hypothetical viability for future formulations: MTN 035

MTN-026 MTN-026 is the first clinical trial to collect safety and pharmacokinetic data on the rectal application of dapivirine gel (0.05%) in a cohort of HIV-uninfected adults. Behavioral Data: User acceptability of the product User-centered suggestions for product design and delivery Satisfaction with the clinical trial experience Suggestions to improve the trials from a user perspective

MTN-033 MTN-033 is one of the first clinical trials involving the rectal application of dapivirine gel (0.05%) in a cohort of HIV-uninfected adults. Assess study gel safety and acceptability, including comparison between Applicator and Self-Administration: User perceptibility Existing product use and satisfaction/needs User-centered suggestions for product design Experiences with the direct observation dosage method

MTN-037 MTN-037/PC-1005 is a Phase 1, open label, sequential dose/VET designed to evaluate the safety and PK of PC-1005 (MIV-150/Zinc Acetate/Carrageenan gel) when administered rectally.  MPT Gel designed to target HIV-1, herpes simplex virus type 2, and HPV. Different Volumes : Acceptability & Tolerability of the product User-centered suggestions for product design and delivery Satisfaction with the clinical trial experience Suggestions to improve the trials from a user perspective

Beyond gel: Diverse modalities… Cis and trans people often report using other rectal products before/after sex. Diverse modalities may accommodate different social/structural circumstances. Different segments of the population may prefer some modalities over others.

MTN 035 First study to systematically examine the acceptability, tolerability and adherence of three placebo formulations in a sample of young cis and trans MSM and trans women in 5 countries. Compare/contrast modalities based on product characteristics and participants’ characteristics and contexts. Assess modality acceptability and tolerability, including best practices learned from participants’ experiences, as MTN explores formulations.

Washout period (~1 week) MTN 035 Sequence N Period 1 (4 weeks) Washout period (~1 week) Period 2 Period 3 A 35 Rectal insert -- Rectal douche Rectal suppository B C D E F

“Scorecard” for prevention modalities Modality Efficacy Low user burden Low Cost Low systemic side effects Reversibility Low risk of Resistance Increases sexual pleasure MPT Daily oral PrEP On demand PrEP ( ) Injectable PrEP PrEP implant Vaginal ring Rectal lube or insert Rectal douche bNAbs/HIV Vaccine *Adapted from original slide courtesy of Dr. Liu.

The way forward! The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. The content is solely the responsibility of the author and does not necessarily represent the official views of funding agencies.