Acceptability of potential rectal microbicide delivery mechanisms for HIV prevention Heather Pines, Pamina Gorbach, Robert Weiss, Kristen Hess, Ryan Murphy, Terry Saunders, Leonardo Colemon, Edward Robbie, Joelle Brown, Ross Cranston, and Peter Anton UCLA Microbicide Development Program Project 3 funded by NIH Grant U19 A

Introduction  Various formulations and devices can be used to deliver rectal microbicides  Potential impact of rectal microbicides on HIV infection rates will depend on adherence, which is likely affected by acceptability  Purpose:  To investigate the acceptability of different rectal delivery methods to inform the development of rectal microbicides

Introduction  Objective:  To measure the acceptability of 3 over-the-counter placebo anorectal products among men and women who practice receptive anal intercourse (RAI)  Study Products: Pre-Seed TM Applicator filled with Lubricant Normosol-R Enema Tucks TM Suppository

Methods  Study Design:  Randomized crossover clinical trial  Study Population:  Men and women recruited from various community sources and screened for inclusion between February 2009 and September 2010  Eligibility Criteria: ≥18 years of age; STI and HIV-negative; history of RAI; no anorectal symptoms of grade 2 or higher at visits 1 and 2; no anorectal herpes outbreak within 30 days of visit 1; no known allergies to components of study products or other anorectal products; not homeless; not pregnant or breastfeeding; not participating in another clinical trial involving anorectal products; willing and able to comply with procedures and give informed consent

Methods  Study Procedures:  Data Collection:  Computer-assisted self-interviews (CASI)  Face-to-face interviews: concomitant medications & AEs  Telephone-computer-assisted self-interviews (T-CASI)

Microbicide Acceptability & Adherence Across Phases of Product Development Continuation/ Maintenance Acceptability Phase I & II Open Market Cost Risk perception Type of partner Access Clinical Trials Stigma General population Effectiveness level Open behavioral conditions ? Adherence Phase IIb, III Product characteristics ( smell, texture, applicator, partner response, impact on sexual pleasure, formulation, side effects) Study Population Protocol requirements Partner characteristics Clinic access Counseling Reporting Methods Other services provided Incentives Partner characteristics Coly A and Gorbach PM. Microbicide Acceptability Research: Recent Findings and Context Evolution. Current Opinion in HIV and AIDS; Oct 2008, Vol. 3, No. 5:

Defining Acceptability  Participants evaluated 11 statements included in CASI questionnaires about product characteristics via likert scale responses (strongly agree, agree, neither agree nor disagree, disagree, or strongly disagree)  I liked using the product  I found the product difficult to use  I found the product inconvenient to use  I found the product painful to use  Using the product irritated my butt  I had no problem using the product  I found that using the product was too runny  I found that using the product interrupted sex  I found that using the product increased my sexual pleasure  I found that using the product increased my partner’s sexual pleasure  My partner liked it when I used the product  Overall acceptability score created by averaging the sum of all individual scores for each statement

Statistical Analysis  Linear random effects model used to estimate a mean acceptability score for each product  Differences between product acceptability scores calculated to determine product preferences  Examined the effects of various covariates on acceptability  Examined whether these covariates affect product preferences (i.e. whether differences between product acceptability scores differed across subgroups of these covariates)  Poisson random effects model used to measure the association between acceptability and adherence

Baseline Characteristics (N=117) Characteristic Males (N=92) n (%) Females (N=25) n (%) Mean Age in Years (SD)39.7 (12.2)39.6 (11.9) Race White African American Other 33 (36) 32 (35) 26 (29) 14 (56) 7 (28) 4 (16) Hispanic21 (23)8 (32) Marital Status Single Married Domestic Partner Other 71 (78) 1 (1) 10 (11) 9 (10) 9 (36) 4 (16) 3 (12) 9 (36) *Numbers may not sum to column totals due to missing data; Percents may not sum to 100% due to rounding; SD = standard deviation.

Baseline Characteristics (N=117) Characteristic Males (N=92) n (%) Females (N=25) n (%) Education < High School Grad High School Grad or GED Some College ≥ College Grad 3 (3) 21 (23) 23 (26) 43 (48) 1 (4) 6 (24) 10 (40) 8 (32) Prior Anorectal Product Use Enema Applicator Suppository 50 (58) 33 (38) 18 (21) 14 (56) 9 (36) 4 (16) No Prior Anorectal Product Use26 (28)8 (32) RAI in the past 2 Weeks Mean # of Times (SD) 50 (56) 2.8 (3.0) 18 (72) 2.9 (2.8) *Numbers may not sum to column totals due to missing data; Percents may not sum to 100% due to rounding; SD = standard deviation.

Product Use in the Past 2 Weeks Significant difference (p < 0.05) between enema & applicator (*), enema & suppository (†), and applicator & suppository (‡).

Anorectal Symptoms and AEs Significant difference (p ≤ 0.1) between enema & nothing (^), applicator & nothing (§), and suppository & nothing (¶). Significant difference (p ≤ 0.1) between enema & applicator (*), enema & suppository (†), and applicator & suppository (‡).

Product Feedback Significant difference (p < 0.05) between enema & applicator (*), enema & suppository (†), and applicator & suppository (‡).

Product Feedback Among those who Reported Sex in the Past 2 Weeks Significant difference (p < 0.05) between enema & applicator (*), enema & suppository (†), and applicator & suppository (‡).

Overall Product Acceptability Scores (N=109) Product Mean Acceptability Score 95% CI Enema3.53.3, 3.6 Applicator3.73.6, 3.8 Suppository3.43.3, 3.5 Product ComparisonDifference95% CI Enema vs. Applicator* , -0.1 Enema vs. Suppository , 0.2 Applicator vs. Suppository*0.30.1, 0.4 *p-value < 0.05

Effect of Covariates on Acceptability (N=109) Covariate Mean Difference in Acceptability p-value Age in years Male Experience Using Products Prior to Study Last Product Use in the Context of Sex ≥ 1 Anorectal Symptoms in the Past 2 Weeks ≥ 1 AEs Related to Product Use in the Past 2 Weeks

Final Model: Acceptability by Age & Gender  Among participants with prior experience using the product, who reported no symptoms and reported using the product in the context of sex at last use p-value for age*product interaction = 0.003; p-value for gender*product interaction = 0.03

Acceptability & Adherence Frequency of Product Use Mean Rate Ratio* (95% CI) Acceptability Score 1.10 (1.01, 1.22) p-value = *For a typical participant whose random intercept is zero.

Summary  Applicator filled with lubricant had the highest overall acceptability score:  Most convenient to use and least runny  Increased participant’s and their partner’s sexual pleasure  Acceptability scores were higher among:  Males  Older participants  Participants who reported no symptoms or AEs in the past 2 weeks  Participants who reported using products in the context of sex at last use  Product preferences differed by age and gender:  Product preferences stronger among females  Females of all ages preferred the applicator  Younger males preferred the applicator, no preferences between products among older males

Discussion  Limitations:  No data on final preferences among products at study exit  No data on frequency of product use in the context of sex/RAI  If people dropped out because they did not like products, estimates of acceptability may be upwardly biased  Strengths:  Assessed acceptability as a multi-dimensional concept through use of a 11 item scale with likert responses  Evaluated acceptability of multiple anorectal products – allowed for a comparison across products  Study sample included RAI experienced males AND females  High retention rate = 89%  Next Steps:  Examine which statement or groups of statements predict adherence best

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