Acceptability of a Novel Vaginal Microbicide During a Safety Trial Among Low-Risk Women by Margaret E

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 infection 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 product 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):184Ð188 data operations manager, Fred Hutchinson Cancer Re- search Center, Seattle. Zeda Rosenberg is scientific director, 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. Interviews were tape-recorded and vention Trials Network, which evaluates sent, since they were not considered at risk transcribed for content analysis. the efficacy of different behaviorally (because of the requirement of condom linked biological HIV prevention strate- use during sex). Results gies. One of the network’s research pri- Study Participants orities is the testing of candidate micro- Procedures In all, 27 women enrolled—16 who were bicides that have completed preclinical Enrolled women were instructed to insert sexually abstinent and 11 who were sex- trials. This Phase I study was the first time 5 ml of the gel into the vagina once daily ually active. Fifteen participants com- that any women had mucosal exposure to for 14 days, beginning 3–5 days after pleted both the once-daily and the twice- this product, and thus the primary aim menses. Following the completion of their daily application phases; the remaining was to assess the gel’s safety profile— next menses, they were given the option 12 women completed only one phase. In specifically, to examine possible changes to “roll over” to a twice-daily regimen for the abstinent cohort, six women com- in vulvar and cervicovaginal mucosal an additional 14 days. Some participants pleted both phases, six completed once- health after seven and 14 days of daily or did not wish to roll over and thus com- daily application and four completed twice-daily exposure. Detailed safety and pleted only the once-daily regimen; to en- twice-daily application. In the sexually ac- toxicity results are presented elsewhere.9 sure sufficient enrollment in the twice- tive cohort, nine women completed both A secondary objective was to assess daily regimen, the protocol permitted phases, one the once-daily application and women’s compliance with instructions for some participants to go directly to that one the twice-daily application. using the method and the product’s ac- phase. The protocol required participants Seventeen participants were white, ceptability to users. to complete acceptability assessments at three were black and seven were Hispan- The study was conducted at two hos- baseline and at days seven and 14, to ic. The women’s ages ranged from 18 to pitals in Rhode Island that are affiliated maintain daily diaries, and to undergo 45 and averaged 31. Most participants had with Brown University; enrollment began four pelvic and two colposcopic exami- had at least a high school education, and in April 1997 and ended about six months nations for each 14 days of enrollment. more than half had completed at least later. Participants were recruited via mul- According to the protocol, eight in 10 sex- some college. tiple sources, including local public media ually abstinent women had to complete Fourteen of the 27 women and two (e.g., newspapers, cable television and the trial with no serious adverse events be- male partners chose to participate in the public service announcements), univer- fore the sexually active cohort began en- unstructured interviews. Three of these sity media, posted flyers and snowballing rollment. Participants were paid $50 for women were interviewed by telephone; referrals from participants in ongoing HIV each study visit and $100 every time they the remainder participated in two focus prevention studies. Women were eligible underwent colposcopy, for a minimum of groups. The male partners who partici- to participate if they were 18–45 years old, $300 and a maximum of $600 for comple- pated provided informed consent. had a regular menstrual cycle with a min- tion of the full study protocol. imum of 18 days between menses and met Acceptability assessments were con- Safety and Side Effects the study criteria for being low-risk—that ducted through face-to-face structured in- Interview data suggested that no perceived is, they had had no STD in the last six terviews. The pretrial assessment explored side effects or symptoms caused major con- months; were sexually abstinent or were previous vaginal product use and pre- cern among the participants. This issue was in a stable, monogamous relationship with conceived perceptions of acceptability. On directly probed during the interviews. a partner who was not known to be HIV- the seventh day, all women were asked Diary data, however, suggested that six positive and was at low risk for HIV; and questions related to the product’s char- sexually abstinent women and two sexu- were not using injection drugs. To be eli- acteristics (e.g., smell, consistency and ally active participants experienced mild gible, women also had to be willing and color) and to the use of the applicator (e.g., or moderate itching or burning with prod-

Volume 32, Number 4, July/August 2000 185 Acceptability of a Novel Vaginal Microbicide

Table 1. Number and percentage distribution of women, by per- One-third of the 22 indication that women were embarrassed ceptions of various characteristics of a microbicide gel in Phase women who completed by the discharge or that they had any emo- I testing, according to frequency of application and to sexual the once-daily regimen tional reactions to the product. One sex- activity, Rhode Island, 1997 reported that the prod- ually active woman noted that she was Characteristic and All Sexually Sexually uct was “wet/drippy” “stressed,” but this was not linked to her frequency of abstinent active at least some of the time, use of the gel. application No. % No. % No. % compared with two- thirds of the 20 women Acceptability: Effects on Sex TOO WET/DRIPPY Once daily who inserted gel twice In acceptability assessments, sexually ac- Never/rarely 15 68 8 67 7 70 daily. (This may reflect tive women were asked whether they Sometimes 5 23 4 33 1 10 the increased volume of agreed or disagreed with several state- Often 1 5 0 0 1 10 Always 1 5 0 0 1 10 product inserted in the ments about the gel’s effects on their sex- twice-daily regimen.) ual pleasure. Two women who used the Twice daily product once a day and one who used it Never/rarely 7 35 3 30 4 40 Most women noted Sometimes 6 30 5 50 1 10 that a vaginal discharge twice daily reported that it interfered with Often 4 20 1 10 3 30 began after 1–2 days of intercourse. Five women from the once- Always 3 15 1 10 2 20 product use. Many re- daily group and six who applied it twice TOO STICKY ported that the gel was daily—about half of each group—report- Once daily clear when ﬁrst admin- ed that it increased their sexual pleasure. Never/rarely 17 77 9 75 8 80 Sometimes 2 9 2 17 0 0 istered but that the dis- About three-quarters in each group Often 2 9 0 0 2 20 charge was “thicker and thought that their partner liked the way Always 1 5 1 8 0 0 lumpier” and white, re- the gel felt. Twice daily sembling cottage cheese. Reﬂecting the lubricating effects of the Never/rarely 12 60 7 70 5 50 Some were concerned product, one woman recorded in her diary Sometimes 4 20 1 10 3 30 Often 2 10 1 10 1 10 that this discharge was a that “sex was better during the study....it Always 2 10 1 10 1 10 symptom of a yeast in- was wetter.” However, three others fection; others said that recorded that although the gel was wet SOILS CLOTHES Once daily because they lacked and lubricating at the beginning of sex, it Never/rarely 15 68 9 75 6 60 other symptoms (e.g., soon became “dry” or “dry and sticky.” Sometimes 6 27 2 17 4 40 A number of issues related to the prod- Often 1 5 1 8 0 0 itching, odor), they were Always 0 0 0 0 0 0 not concerned. uct’s use during sex were covered in the Vaginal specimens focus-group discussions. Participants in Twice daily Never/rarely 9 45 4 40 5 50 taken on days seven and these groups (including one of the two cou- Sometimes 8 40 4 40 4 40 14 of the study were ex- ples who participated) indicated that prod- Often 2 10 2 20 0 0 amined microscopically uct discharge was present on the surface Always 1 5 0 0 1 10 for signs of yeast infec- of the condom after sex. The wife of one Total na 100 na 100 na 100 tion. In almost 80 couple, however, noted that after inter-

Note: na=not applicable, because some women did not respond to all statements. woman-weeks of prod- course, the discharge was reduced. A uct exposure, one woman whose partner was not present re- woman had a sympto- ported that while she had noticed the dis- uct use, in most cases throughout the du- matic candida infection; another had an charge, she could not recall her partner’s ration of the study. Three women (two ab- asymptomatic yeast infection. There was commenting on it either during or after sex. stinent and one sexually active) recorded no association between the discharge, difficulty urinating. One sexually active which was commonly reported, and clin- Overall Evaluation woman recorded a feeling of fullness with ical infections, which were rare. At the 14-day assessment, women were some pain during the last three days that The topic that generated the most dis- asked, “If BufferGel were approved for she used the product twice daily. cussion during the focus-group inter- vaginal use, would you use it?” Four of 14 Clinical data confirm the women’s in- views—regardless of whether women abstinent women and four of 11 sexually terview and diary reports. No women ex- were abstinent or sexually active, and active participants said they would not; perienced serious side effects associated whether they used the product once or two women did not complete the assess- with use of the gel; two participants de- twice daily—was the amount and quali- ment. An open-ended question clarified veloped vaginal candida infections in the ty of vaginal discharge associated with the reasons that women would not use the course of the study.10 In the absence of a product use. Although participants re- product: They lacked a current sexual control group, and given that none of the ported some variation in the degree of partner, had a monogamous partner, pre- side effects were severe, the reported side messiness associated with the discharge ferred a disposable applicator, found the effects could not be conclusively associ- and in its volume and consistency, prod- product too messy, were able to negotiate ated with product use. uct discharge was a lively topic. condom use or did not perceive them- None of the women interviewed noted selves to be at risk. Acceptability: Product Characteristics any odor associated with the gel during Focus-group participants were asked a Several women perceived the product to use. Diary data generally confirmed in- similar question: “If this product was on be “wet/drippy” or “sticky,” although this terview data regarding odor, although one the market, was available today, would experience varied depending on how woman recorded that the “discharge had you use it or recommend it to your daugh- often the women applied the gel (Table 1). a metallic odor.” The diaries contained no ter [or to] a friend?” Responses to this

186 Family Planning Perspectives question were nearly all positive. Al- tampon use as soon as she remembered. ficult at best. The addition of qualitative though some participants did not perceive Although none of the sexually active cou- data facilitates a fuller interpretation of the themselves to be in need of such a micro- ples were particularly happy about using quantitative data. bicide because of their sexual behavior or condoms, they reported always using There are some limitations of the study perception of low risk, most thought that them. Several women noted that remem- and its findings. First, because this study the product would be an important way bering to fill in the daily diaries was dif- was designed primarily to assess the prod- for a woman to protect herself. One ficult. Adherence to the dosing schedule uct’s safety and toxicity, it required exag- woman, however, thought there was an was virtually perfect, according to daily gerated doses; this could have a negative important role for a microbicide product diary records, follow-up interviews and impact on acceptability. The limitations yet said she would prefer other methods: focus-group responses. and potential bias of assessing accept- “There is something psychologically Although no woman had previously ability among small groups of people dur- comforting about physical barriers...which had a colposcopy, none reported that this ing experimental testing have been dis- doesn’t happen with BufferGel....I don’t was a problem. In fact, women were able cussed elsewhere.11 have problems negotiating protection to view the entire process on a video Second, we were unable to validate self- when I’m having sex.” screen, and many reported that this was a reports of product use. No specific mea- Since product discharge was obvious- valuable and interesting aspect of the ex- sures were developed to address this con- ly an important issue, we probed whether amination. Several women expressed re- cern, though we are confident that the gel the messiness or cottage cheese–like con- lief that they had had the opportunity to was applied as required, partly because sistency would determine whether par- be “so thoroughly examined” and to know of the amount of it that clinical staff re- ticipants used the product if it were avail- that they were “clean” and “healthy.” ported observing during pelvic and col- able. Some women responded that they Women were queried about what had poscopic examinations. would try such a product, but they would motivated them to enroll in the study. Sev- Third, because of the protocol design, want to see what happened with the con- eral responded that they had desired to be women enrolled in this study had a low sistency and “clumpiness” during sex. part of “such a good cause” or to “give risk of acquiring HIV. They would not like- Several women made the distinction be- something back to society.” In addition to ly be a priority population for the market- tween “real life” and their study experi- responses reflecting altruism in general, ing and use of vaginal microbicides. Prod- ences. They noted that in “real life,” a some participants reported a specific de- uct acceptability may differ among women woman would not be using the product sire to help women, since women are at in- who are at increased risk of disease acqui- every day or twice a day (although this creased risk for HIV infection. One par- sition. Also, condom use was required to generated interesting discussions about ticipant reported that she always felt upset prevent possible exposure to the product use among sex workers). that women may contract the virus dur- among participants’ male partners. As A male interviewer asked the two men ing one act of unprotected intercourse but such, no experiential information could be who participated in the focus group, “If that “it’s not the same for the man.” She gathered about product acceptability dur- it came to the time that we thought this commented: ing unprotected sex. Finally, we had diffi- could go on to the next phase of the study, “I was very excited knowing that [if culties recruiting male partners for focus would you be willing to participate in a women] choose to have sex with different groups and are unable to adequately dis- male safety study where you would ex- men,…they can put something in them to cuss partners’ reactions to the product. pose the penis to the product directly?” protect themselves....So that’s why So, what has been learned about this One man responded that he would par- through the whole thing I just thought product and its potential acceptability as ticipate, since his partner had already been about that—the power of women.” a vaginal microbicide? Most important, in the study; the other male did not re- the low-risk women who participated in spond to this question. Discussion this safety trial reported that, given their To our knowledge, the study we have de- perception of personal risk and the prod- Adherence scribed was the first Phase I safety and tox- uct’s presumably reasonable affordabili- The protocol called for the study to be icity vaginal microbicide trial to include ty, they would use the gel to prevent STD replicated in four international sites if the in-depth assessments of product accept- infection. In view of this finding, and product was found to be safe and acceptability. It is not conventional to include a given that continued prevention efforts able; furthermore, the protocol could serve product acceptability component in a aimed at women are likely to heighten as a model for future Phase I microbicide Phase I safety trial, but we believe that this their perceived risk, this product has po- trials. Consequently, information on par- approach is both sensible and feasible. By tential for significant acceptance among ticipants’ (and their partners’) willingness tracking use and acceptability early on, higher-risk women. The acceptability of and ability to complete the trial, with its even among women who are at low risk microbicide products changes as the intensive product use and follow-up re- relative to other populations, we can learn user’s perspective changes.12 Therefore, quirements, was considered important. In- much about whether the product will be higher-risk women may be even more mo- terview, diary and focus-group data ad- used in future clinical trials or if it becomes tivated to try such a product. On the basis dressed these issues and allowed women available in the marketplace. of their perceived risk, an estimated 20 (and men) to describe their experience in The combination of qualitative and million U.S. women would have some in- the trial. quantitative interviews allows assessment terest in using a microbicide product, de- One participant reported having broken of variability across women regarding the pending on its specifications and cost.13 a study rule. The woman had forgotten product and its use during the trial. Phase This market is likely to grow substantial- that she was not allowed to use tampons I studies have limited numbers of partic- ly as perceived risk converges with actu- during the interval between once- and ipants, which makes statistical analysis al risk and as women learn more about the twice-daily use, but had discontinued and interpretation of quantitative data dif- prevalence of viral STDs (especially her-

Volume 32, Number 4, July/August 2000 187 Acceptability of a Novel Vaginal Microbicide pes and human papillomavirus). for women who risk abuse or the loss of 8(1):285–293; and Elias CJ and Coggins C, Female-con- Half of the women who used the prod- a relationship when using a microbicide trolled methods to prevent sexual transmission of HIV, uct during sex reported that it enhanced for protection. While we do not have ad- AIDS, 1996, 10(3):543–551. sex, and nearly three-quarters reported equate data to answer this question, our 2. Darroch JE and Frost JJ, Women’s interest in vaginal that they thought their partners liked the findings suggest that women are unlike- microbicides, Family Planning Perspectives, 1999, feel of the gel during sex. This finding is ly to be able to use this product clandes- 31(1):16–23. similar to ones reported for other micro- tinely. A majority of the sexually active 3. Stein ZA, HIV prevention: the need for methods bicide products,14 and it is perhaps one of women and the two male partners inter- women can use, American Journal of Public Health, 1990, the most promising results of all. viewed observed that sex “felt different” 80(4):460–462; and Elias CJ and Heise LL, Challenges for In its current formulation, this product and noted that the product may be dis- the development of female controlled vaginal microbicides, AIDS, 1994, 8(1):1–9. has possible drawbacks. The most im- charged on the penis. However, a few portant of these is the messiness, stickiness women and both men noted that it would 4. Sobo EJ, Choosing Unsafe Sex: AIDS-Risk Denial Among or cottage cheese–like consistency of the be more difficult to detect that sex was Disadvantaged Women, Philadelphia: University of Penn- product following application. Several “different” if the partner was a casual part- sylvania Press, 1995. women suggested that the product be re- ner. This is an important factor to exam- 5. Ibid.; Alliance for Microbicide Development, Micro- formulated into a suppository. It should ine in future microbicide research, espe- bicides: research and development status as of Septem- be noted that the volume of gel required cially as it pertains to women with ber 1998, Takoma Park, MD: Alliance for Microbicide De- velopment, 1998; and Rosenthal SL et al., Topical for this safety trial, especially during the multiple sexual partners. microbicides: current status and research considerations twice-daily dosing regimen, could be To assess the relevance of these findings for adolescent girls, Sexually Transmitted Diseases, 1998, greater than amounts that would be ap- in international settings, Phase I studies 25(7):368–377. plied in actual use. Further acceptability of the product, including similar assess- 6. Kreiss J et al., Efficacy of nonoxynol-9 contraceptive studies of varying product volumes in ments of its acceptability, have been un- sponge use in preventing heterosexual acquisition of HIV higher-risk populations (e.g., including dertaken in India, Malawi, Thailand and in Nairobi prostitutes, Journal of the American Medical As- commercial sex workers or women in Zimbabwe. Key research questions at in- sociation, 1992, 268(4):477–482; and Martin H et al., Safe- monogamous relationships with HIV-international sites include the product’s af- ty of nonoxynol-9 vaginal gel in Kenyan prostitutes, Sex- fected or high-risk partners) are needed fordability and accessibility, how prein- ually Transmitted Diseases, 1997, 24(5):279–283. to assess the required volume and the gel’s troduction educational strategies may 7. Roddy RE et al., A controlled trial of nonoxynol 9 film associated physical attributes as potential facilitate product acceptance and, of to reduce male-to-female transmission of sexually trans- barriers or facilitators of product use. Ide- course, whether women will be able to use mitted diseases, New England Journal of Medicine, 1998, ally, these studies would be done in the ab- the product in privacy and without part- 339(8):504–510. sence of condoms, to illuminate the rela- ner knowledge, if necessary. (Stability test- 8. ReProtect, BufferGel Investigator’s Brochure 1997, Bal- tionship between product volume, ing is not part of the international trials.) timore: ReProtect. physical attributes and semen. Cultural beliefs and current sexual prac- 9. Mayer KH, Peipert J and Fleming T, The safety and As many women noted, if the product tices of women and men who are at risk tolerability of BufferGel, a novel vaginal microbicide is proven efficacious, this could easily out- will be examined. studied in U.S. women, Clinical Infectious Diseases, 2000 weigh the “nuisance factors.” Participants’ The positive safety and toxicity results (forthcoming). 15 comments throughout the study suggest of the trial, along with the product’s ac- 10. Ibid. that women will need to undergo exten- ceptability, point up an urgent need to sive education about how they should op- move ahead with additional testing. As 11. Keller A, Contraceptive acceptability research: util- timally apply and use this product, and other vaginal microbicide products be- ity and limitations, Studies in Family Planning, 1979, 10(8/9):230–237. what they may experience with product come ready for Phase I testing, it is im- use (e.g., discharge). Such education may portant that acceptability assessments be 12. Heise L, Beyond Acceptability: Reorienting Research on enhance the product’s acceptability, as considered a key part of clinical trials. Contraceptive Choice, London: Reproductive Health Mat- ters, 1997. women may be able to take measures in anticipation of product side effects (e.g., References 13. Darroch JE and Frost JJ, 1999, op. cit. (see reference the use of panty liners for those concerned 1. Gupta GR and Weiss E, Women and AIDS: Developing 2). with leaking). a New Health Strategy, International Center for Research 14. Steiner M, Spruyt A and Joanis C, Acceptability of An important question that this study on Women (ICRW) Policy Series, Washington, DC: ICRW, spermicidal film and foaming tablets among women in cannot answer, but that is perhaps key for 1993; Heise L and Elias C, Transforming AIDS preven- three countries, International Family Planning Perspectives, tion to meet women’s needs: a focus on developing coun- 1995, 21(3):104–107. all microbicides, is whether the gel could tries, Social Science and Medicine, 1995, 40(7):931–943; Stone be used without the knowledge of a AB and Hitchcock PJ, Vaginal microbicides for prevent- 15. Mayer KH, Peipert J and Fleming T, 2000, op. cit. (see woman’s partner. This may be important ing the sexual transmission of HIV, AIDS, 1994, reference 9).

188 Family Planning Perspectives