Acceptability of a Novel Vaginal Microbicide During A Safety Trial Among Low-Risk Women By Margaret E. Bentley, Kathleen M. Morrow, Andrew Fullem, Margaret A. Chesney, Scott D. Horton, Zeda Rosenberg and Kenneth H. Mayer ingredient in many contraceptives) have Context: The increasing recognition that women who are unable or unwilling to discuss or use been tested among high-risk populations condoms with their sexual partners need female-controlled methods for preventing sexually in Phase II or III trials. While some of these transmitted diseases (STDs), including HIV, has led to considerable focus on the development products have been proven effective in of vaginal microbicides. While many such products are being tested for safety and effective- preventing infection with several sexual- ness, clincal trials generally overlook another key factor in a product’s impact on infection rates— ly transmitted pathogens,6 nonoxynol-9 its acceptability to users. film did not reduce the rate of HIV, gon- Methods: A Phase I clinical trial of a microbicidal gel included an assessment of the product’s orrhea or chlamydia infection in a large 7 acceptability among 27 low-risk participants. Information on acceptability was gathered from trial conducted in Cameroon. structured interviews, participants’ daily diaries and unstructured exit interviews. If a product is to have an impact on in- fection rates, it must be not only safe and ef- Results: Participants reported only minor side effects of product use, such as itching, burning fective in preventing STDs, but also accept- and difficulty urinating; two women developed candida infections while participating in the study. able to potential users. In this article, we None of the side effects could be conclusively linked to use of the gel. Some women noted prod- uct discharge and messiness as drawbacks of the method, but this experience varied accord- Margaret E. Bentley is associate chair and associate pro- ing to how often the women applied the gel. For example, one-third of those who used it once fessor, Department of Nutrition, School of Public Health, daily said that at least some of the time, it was too “wet or drippy,” compared with two-thirds of and fellow, Carolina Population Center, University of women who inserted the gel twice a day. However, participants considered these “nuisance North Carolina, Chapel Hill. Kathleen M. Morrow is as- sistant professor, Centers for Behavioral and Preventive factors” that could be outweighed by the potential protective characteristics of the product. The Medicine, The Miriam Hospital and Brown University majority reported that they would use the product if it were available and proven efficacious, and School of Medicine, Providence, RI. Andrew Fullem is if they perceived that they were at risk of STD infection. director, HIV/AIDS Surveillance, Massachusetts De- partment of Public Health, Boston. Margaret A. Ches- Conclusions: Additional testing of this product is urgently needed. Furthermore, as other prod- ney is professor, Center for AIDS Prevention Studies, Uni- ucts approach Phase I testing, acceptability assessments should be a key component of clini- versity of California at San Francisco. Scott D. Horton is cal trials. Family Planning Perspectives, 2000, 32(4):184–188 data operations manager, Fred Hutchinson Cancer Re- search Center, Seattle. Zeda Rosenberg is scientific di- rector, HIV Prevention Trials Network, Family Health International, Arlington, VA. Kenneth H. Mayer is pro- n recent years, the testing and evalua- ners about the use of barrier methods for fessor, Brown University AIDS Program, Providence, RI, tion of topical microbicides to prevent STD prevention. This is true in developed and Memorial Hospital, Pawtucket, RI. This work was sexually transmitted diseases (STDs), in- as well as developing countries, particu- supported by the HIV Network for Prevention Trials I (HIVNET), sponsored by the National Institute of Allergy cluding HIV, have been the focus of con- larly among women who are disadvan- and Infectious Diseases, National Institutes of Health, siderable attention. This focus reflects in- taged by poverty or gender discrimination, through contract N01-AI-35176 with Abt Associates; con- creasing recognition that female-controlled who may not wish to compromise their tract N01-AI-45200 with the Fred Hutchinson Cancer Re- methods are necessary to protect women relationships by questioning their partners’ search Center; and subcontracts with Memorial Hospi- fidelity.4 tal, Women and Infants Hospital, the Denver Public who are unable or unwilling to discuss or Health Department, Fenway Community Health Cen- 1 use condoms with their sexual partners. Several dozen microbicide products are ter, Howard Brown Health Center, New York Blood Cen- A large, nationally representative survey in various stages of development or test- ter, New York University Medical Center, San Francisco of sexually active U.S. women reported that ing.5 New products undergo lengthy, mul- Department of Public Health, University of Pennsylva- 80% would have been interested in using tiphased safety and toxicity studies before nia and University of Washington. ReProtect supplied BufferGel for the study. The authors are grateful for the a vaginal microbicide product at some time the Food and Drug Administration ap- dedication and commitment of participants, the efforts during the past, and 40% would currently proves them for use in the United States. of site staff and the contributions of HIVNET commu- be interested, assuming that the product Preclinical studies evaluate a product’s ac- nity advisory board members. We thank the following was protective against STDs.2 Although the tivity in either cell cultures or animal mod- individuals for their assistance: Fran Bettencourt, Susan Kelly and Amy Cooper conducted expert clinical and in- results of that survey must be interpreted els. Once these studies have been com- terview collection procedures; Rochelle Rosen and David cautiously because of the limitations asso- pleted, Phase I clinical studies begin; these Celentano conducted focus groups; Lynda Emel and Cliff ciated with asking hypothetical questions trials are designed to assess safety in low- Kelly provided data management and analysis assistance; of “potential” users, they suggest a demand risk populations. Phase II trials assess safe- Kevin Whaley and Thomas Moench provided insights among U.S. women for female-controlled ty in higher-risk populations and test the for protocol development and interpretation; David Ce- lentano and Kenrad Nelson collaborated on a uniform STD prevention methods. biological plausibility of a given approach. protocol for domestic and international Phase I studies; There is clearly a need for such products Phase III studies evaluate the efficacy of the Michael Gross and Ann Koonce contributed to the de- in settings where, in a variety of ways, gen- product in high-risk populations. velopment of instruments; Ward Cates, Jr., Julie Welch, der inequality places women at sexual Additionally, products currently mar- Leslie Hjeldness and staff at Family Health Internation- 3 al assisted with protocol development and manuscript risk. For example, in many geographic keted for other purposes may be tested for preparation; and Frances Dancy prepared the manu- and sociocultural settings, women may be efficacy in preventing STDs. A number of script. This article does not necessarily reflect the views, reluctant or unable to talk with their part- preparations containing nonoxynol-9 (an policies or endorsement of the U.S. government. 184 Family Planning Perspectives report on the acceptability to users of a novel able to give informed consent and to com- ease of use, comfort, cleaning and dis- vaginal microbicide, BufferGel, which is in plete a daily study diary. posability). On day 14, women who com- the first stage of safety and toxicity testing. Participants agreed, for the duration of pleted the trial were asked whether they The gel is designed to prevent disease the study, to abstain from using injection would use this project if it was approved transmission by promoting mild acidity drugs and vaginal products (such as lubri- for vaginal use. For sexually active (pH less than five), because HIV and other cants, tampons, vaginal drying agents and women, questions addressed the use of STD pathogens are not viable outside the douches), and to insert the microbicide as the product before, during and after sex, vagina’s usual pH of around seven; in an- required by the protocol and immediately as well as their partner’s reactions to it. imal studies, the product has maintained prior to intercourse. Sexually active partic- In the daily diary, participants were asked the vaginal pH around 4.5 or lower. It also ipants agreed to have vaginal intercourse to record when and how often they insert- is intended to prevent conception and has at least two times per week, using nonlu- ed the product and whether they experi- sufficient buffer capacity to acidify ap- bricated condoms provided by the study, enced any side effects, embarrassment or proximately twice its own volume in while sexually abstinent participants agreed emotional reactions. Finally, unstructured human semen. The colorless, odorless gel to continue to refrain from intercourse. exit interviews were completed with both is packaged in a six-inch white syringe- The study’s protocol and ethical proce- women and their partners who chose to par- style applicator tube, which administers dures were approved by university and ticipate. Unstructured interviews allowed doses of 5 ml.8 hospital institutional review boards and study participants to freely discuss their ex- the Office of Protection from Research perience of completing a rigorous study, Methods Risks. Sexually active women were re- their experience with and perceptions about Study Objectives and Design quested to discuss the study and its rules the microbicide, and reasons they would or The study was conducted as part of the with their partner, but the male partners would not use the product if it were avail- National Institutes of Health’s HIV Pre- were not asked to provide informed con- able.