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 A1060614

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-SeedTM Applicator

filled with LubricantNormosol-R Enema TucksTM 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

AcceptabilityPhase I & II

Open MarketCostRisk perceptionType of partnerAccess

Clinical Trials

StigmaGeneral populationEffectiveness levelOpen behavioral conditions

?

AdherencePhase IIb, III

Product characteristics(smell, texture, applicator,

partner response, impact on sexual pleasure, formulation, side effects)

Study PopulationProtocol requirementsPartner characteristics

Clinic accessCounselingReporting MethodsOther services providedIncentivesPartner 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: 581-586

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)

RaceWhiteAfrican AmericanOther

33 (36)32 (35)26 (29)

14 (56)7 (28)4 (16)

Hispanic 21 (23) 8 (32)Marital Status

SingleMarriedDomestic PartnerOther

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 GradHigh School Grad or GEDSome College≥ College Grad

3 (3)21 (23)23 (26)43 (48)

1 (4)6 (24)

10 (40)8 (32)

Prior Anorectal Product UseEnemaApplicatorSuppository

50 (58)33 (38)18 (21)

14 (56)9 (36)4 (16)

No Prior Anorectal Product Use 26 (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

Used Product ≥ 3 Times

75% 76%66%

Enema (N=103)Applicator (N=103)Suppository ( N=104)

Last Product Use in the Context of Sex (before/during/after)‡

71%82%

57%

Enema (N=84)Applicator (N=83)Suppository (N=86)

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

Anorectal Symptoms and AEs

0.180.150.1165048543689320.130.0873786407766992

0.220.163461538461538

Nothing (n=115)Enema (n=103)Applicator (n=103)Suppository (n=104)

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 (‡).

57%28% 25%

69%

14% 10%43% 28% 14%

% Strongly Agree or Agree

Enema (n=103) Applicator (n=103) Suppository (n=104)

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 (‡).

31% 35%35% 45%14% 21%

% Strongly Agree or Agree

Enema (n=84) Applicator (n=83) Suppository (n=87)

Overall Product Acceptability Scores (N=109)

ProductMean

Acceptability Score

95% CI

Enema 3.5 3.3, 3.6Applicator 3.7 3.6, 3.8Suppository 3.4 3.3, 3.5Product Comparison Difference 95% CIEnema vs. Applicator* -0.2 -0.4, -0.1Enema vs. Suppository 0.1 -0.1, 0.2Applicator vs. Suppository*

0.3 0.1, 0.4

*p-value < 0.05

Effect of Covariates on Acceptability (N=109)

Covariate

Mean Difference

in Acceptabilit

y

p-value

Age in years 0.01 0.04Male 0.21 0.04Experience Using Products Prior to Study

0.16 0.04

Last Product Use in the Context of Sex

0.32 0.001

≥ 1 Anorectal Symptoms in the Past 2 Weeks

-0.33 0.001

≥ 1 AEs Related to Product Use in the Past 2 Weeks

-0.39 0.001

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

3.2

3.4

3.6

3.8

4

20 30 40 50 20 30 40 50

Males Females

Enema Applicator Suppository

Mea

n A

ccep

tabi

lity

Sco

re

Age (years)

Acceptability & Adherence

Frequency of Product Use

Mean Rate Ratio* (95% CI)

Acceptability Score

1.10 (1.01, 1.22)

p-value = 0.049*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

Thank you, questions?