AIDS Behav DOI 10.1007/s10461-014-0793-0 ORIGINAL PAPER Rectal-Specific Microbicide Applicator: Evaluation and Comparison with a Vaginal Applicator Used Rectally Alex Carballo-Die´guez • Rebecca Giguere • Curtis Dolezal • Jose´ Bauermeister • Cheng-Shiun Leu • Juan Valladares • Lisa C. Rohan • Peter A. Anton • Ross D. Cranston • Irma Febo • Kenneth Mayer • Ian McGowan Ó Springer Science+Business Media New York 2014 Abstract An applicator designed for rectal delivery of clinical trials. Further attention is needed to develop user- microbicides was tested for acceptability by 95 young men friendly, quick-acting rectal microbicide delivery systems. who have sex with men, who self-administered 4 mL of placebo gel prior to receptive anal intercourse over Resumen Un aplicador disen˜ado para administrar los mi- 90 days. Subsequently, 24 of the participants self-admin- crobicidas rectales fue probado para determinar su acept- istered rectally 4 mL of tenofovir or placebo gel over abilidad por 95 hombres jo´venes que tienen sexo con hombres, 7 days using a vaginal applicator, and compared both quienes auto-administraron 4 mL de un gel placebo antes del applicators on a Likert scale of 1–10, with 10 the highest sexo anal receptivo durante 90 dı´as. Posteriormente, 24 de los rating. Participants reported high likelihood to use either participantes auto-administraron rectalmente 4 mL de un gel applicator in the future (mean scores 9.3 and 8.8 respec- tenofovir o placebo durante 7 dı´as usando un aplicador vagi- tively, p = ns). Those who tested both liked the vaginal nal, y compararon ambos aplicadores en una escala Likert de 1 applicator significantly more than the rectal applicator (7.8 a 10, 10 siendo la calificacio´nma´s alta. Los participantes vs. 5.2, p = 0.003). Improvements in portability, conspic- reportaron alta probabilidad de usar cualquiera de los dos uousness, aesthetics, tip comfort, product assembly and aplicadores en el futuro (calificacio´n media 9.3 y 8.8, re- packaging were suggested for both. This rectal-specific spectivamente, p = ns). A los que probaron ambos les gusto´ applicator was not superior to a vaginal applicator. While significativamente ma´s el aplicador vaginal que el rectal (7.8 likelihood of future use is reportedly high, factors that vs. 5.2, p = 0.003). Se dieron sugerencias para mejorar la decrease acceptability may erode product use over time in portabilidad, visibilidad, este´tica, comodidad de la punta, A. Carballo-Die´guez (&) Á R. Giguere Á C. Dolezal Á R. D. Cranston C.-S. Leu Á J. Valladares Department of Medicine, University of Pittsburgh, Pittsburgh, HIV Center for Clinical and Behavioral Studies at New York PA, USA State Psychiatric Institute and Columbia University, Unit 15, 1051 Riverside Drive, New York, NY 10032, USA I. Febo e-mail: [email protected] Department of Pediatrics, Gama Project, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA J. Bauermeister Health Behavior & Health Education, University of Michigan K. Mayer School of Public Health, Ann Arbor, MI, USA Fenway Health, The Fenway Institute, Boston, MA, USA L. C. Rohan I. McGowan Department of Pharmaceutical Sciences, School of Pharmacy, Department of Obstetrics, Gynecology, and Reproductive University of Pittsburgh, Pittsburgh, PA, USA Sciences, University of Pittsburgh and the Center for Family Planning Research, Magee-Womens Research Institute, P. A. Anton Pittsburgh, PA, USA Department of Medicine, Center for HIV Prevention Research, UCLA AIDS Institute, David Geffen School, University of Medicine at UCLA, Los Angeles, CA, USA 123 AIDS Behav ensamblaje y embalaje de ambos aplicadores. Este aplicador especı´ficamente para uso rectal no fue superior al aplicador vaginal. Aunque se reporto´ una alta probabilidad de uso en el futuro, los factores que disminuyen la aceptabilidad podrı´an afectar el uso del producto con el tiempo en los ensayos clı´nicos. Se necesita enfocar ma´s atencio´neneldesarrollode sistemas de administracio´n de microbicidas rectales que sean fa´ciles de usar y ra´pidas. Keywords HIV prevention Á Young MSM Á Rectal microbicides Á Applicators Á Delivery systems Á Acceptability Á USA Á Puerto Rico Fig. 1 Vaginal microbicide applicator Introduction overwrap that for some required a sharp object to open. One of the participants said that applicator-related prob- Men and women who practice anal intercourse often use lems resulted in using less than the specified amount of gel lubricants to facilitate penetration [1–3]. If an affordable and on two occasions. There were no differences in accept- acceptable lubricant included anti-HIV agent(s), it could ability ratings by gender. decrease HIV transmission risk during receptive anal inter- Nevertheless, when an applicator-based delivery system for course (RAI). Over the past decade, research efforts have RM (the same one used in Anton et al. [5] trial) was compared been focused on developing a rectal microbicide gel (RM). to enema or suppository, Pines et al. [7] found that the appli- Lubricants are most frequently applied during sex on the cator filled with lubricant received the highest overall penis or on the anus with fingers in volumes ranging acceptability score and was used more frequently than the approximately from 1 to 4 tablespoons [1]. To deliver a other products by those who hadRAI in theprior 2 weeks.This microbicide on the vulnerable rectal mucosa, studies to- study involved 117 HIV-uninfected males and females (79 and date have used applicators. Unfortunately, RM applicators 21 % respectively) who engaged in RAI and participated in a have encountered sub-optimal acceptability. For example, 6-week randomized crossover acceptability trial. However, in the first human trial of a potential RM, Gross et al. [4] Pines et al. [7] caution that the magnitude of differences used a nonoxynol-9 (N9) contraceptive gel delivered with between complete product acceptability scores differed by an applicator consisting of a plastic pouch with a long stem age, gender, and data collection mode [computer assisted self- ending in a snap-off tip. In this trial of 35 male couples, interviews (CASI) and a telephone audio CASI-T-ACASI]; 68 % of receptive participants reported applicator-related furthermore, significant differences disappeared with age discomfort. Also, 54 % of all participants stated they among males and diminished with age among females. Fur- would not use the gel, and applicator features figured thermore, patterns in complete product acceptability scores prominently among dislikes noted in open-ended com- were not consistent across data collection modes. ments. Some receptive partners reported rectal distension Given that problems with the applicator may negatively that they attributed to release of air with the gel; others affect adherence to product use and product acceptability, disliked the sharp edges at the tip of some applicators after which are critical features in early clinical trials, a rectal- removal of the twist-tab opener, the applicator’s large size specific applicator was designed for rectal delivery of a which made it not easily portable, and the applicator’s microbicide or placebo gel during RM trials. This work, appearance that was judged ‘‘tampon like.’’ conducted under an American Foundation for AIDS In a subsequent RM trial [5] the study gel was delivered Research grant (amfAR-106765-41-RGMC, Carballo-Die´- with a vaginal applicator consisting of a barrel with plunger guez PI) sought to develop an inexpensive rectal applicator and a cap (Fig. 1). An evaluation of male and female user that could be used across RM trials to ensure ease of use, acceptability of the product [6] highlighted that although comfort, and effective delivery of microbicide gel with a 58 % of the participants (N = 36) rated the applicator in wide range of dose volumes for both women and men who the upper third of a 10-point scale, several problems related have RAI. The HIV Center for Clinical and Behavioral with it were identified: that it hurt upon insertion; it was Studies, in partnership with PATH, developed specifications difficult to handle; it had no tactile indicators to signal for the rectal applicator based on input from experts working when the barrel was sufficiently inserted in the rectum, no in the field of RM. The rectal applicator was designed indicator (like a ‘‘click’’) that the gel was ejected, and no according to product specifications through an iterative grips to facilitate product delivery; and it came inside an process with HTI Plastics (Lincoln, NE), the manufacturer of 123 AIDS Behav has been established. A subset of participants had the chance to compare both applicators. The study took place at three sites: (the University of Pittsburgh in Pittsburgh, PA; Fenway Health in Boston, MA; and the University of Puerto Rico in San Juan, PR). Study candidates were recruited between December 2010 and June 2012 from clinics, bars, clubs, newspaper advertisements and social networks. Recruitment materials indicated that the investigators were looking for young men who have sex with men (YMSM), ages 18–30, for a study about their sexual health and their feelings about inserting rectally a placebo gel resembling a microbicide gel currently under development Fig. 2 RM applicator prior to receptive anal sex. the vaginal applicator commonly used in vaginal microbi- Stage 1A: Screening cide trials. The rectal applicator used the Fleet Comfort TipTM that has been commercialized for rectal administra- Participants underwent a pre-eligibility screen by phone or tion of enemas for decades. Further compatibility and sta- in person to determine age, same sex behavior, and pre- bility testing was conducted with four rectal placebo sumed negative HIV status. Those who passed pre- formulations by (Magee-Womens Research Institute) which screening were invited to the clinic for in-person screening led to further product improvements. The rectal applicator (Visit 1) to enroll in Stage 1A (see Fig.