Acceptability and performance of a nonwoven device for vaginal drug delivery among women and their male partners in KwaZulu-Natal, South Africa.

Background: Multipurpose prevention technologies are needed to provide protection against HIV and sexually transmitted infections. Gel-based vaginal microbicides inserted via an applicator are prone to leakage. A novel device for vaginal drug delivery was developed to contain gel-based formulations, aiming to improve gel retention and reduce leakage. The objectives of this study were to assess acceptability and performance of a nonwoven vaginal delivery device. Methods: A nonwoven vaginal delivery device was prepared, pre-saturated with a commercially available water-based lubricant, with a finger pocket for insertion and string for removal. Quantitative and qualitative methods were used to collect data from interviews with 40 women and 10 male partners recruited from a sexual and reproductive health clinic in Durban, KwaZulu-Natal, South Africa. Women wore one device in the clinic and one device overnight or with their partner during intercourse. The primary endpoint was acceptability including comfort, ease of insertion and removal, and opinions on device attributes. Results: Most women said the device was 'easy' to insert and remove. Six women reported leakage after insertion and 34 reported having sexual intercourse while wearing the device. One woman was lost-to-follow-up and five women only wore the device overnight because their partners did not agree to intercourse with the inserted device. The best-liked attribute was the device's lubrication (22 women, 7 men); the least-liked was the removal string (9 women, 8 men). Conclusions: Data are promising for further development of this nonwoven device for vaginal drug delivery. Plain English summary Multipurpose prevention technologies (MPTs) that protect against HIV and sexually transmitted infections (STIs) are urgently needed. A variety of vaginal gel-based products are actively being researched; however, these products can often have challenges with vaginal leakage and retention. This research investigates the acceptability and performance of a nonwoven device to deliver vaginal gel formulations. The gel used in this study was a currently available marketed personal lubricant. In South Africa, 40 women (and 10 male partners) were recruited and given the opportunity to comment on various device attributes after insertion, overnight wear and sexual intercourse with their male partners. Generally, participants found the device easy to use and acceptable, where many factors possibly contributed to the device's acceptability (i.e., similarity to tampons, saturation with lubricant, minimal leakage, ease of insertion, comfort during intercourse and the male partners' willingness to have vaginal intercourse with the device in place). Further studies of the vaginal delivery device for acceptability, safety and efficacy using a gel-based formulation with an active ingredient are warranted.

Using scratch card technology for random allocation concealment in a clinical trial with a crossover design.

BACKGROUND: To avoid selection bias in clinical trials, random allocation concealment is crucial to ensure that participants and or researchers remain unaware of assignments. PURPOSE: We aimed to design an allocation concealment method that reduced the possibility of selection bias for a randomized, open-label, crossover trial to evaluate device function of four female condom (FC) types. METHODS: Using scratch card technology, we devised a simple method of concealment, whereby the treatment sequence was printed on a single card for each participant, and the codes for each treatment in the sequence were concealed beneath foil squares on a stiff A6-sized card. On the first and subsequent follow-up visits, the foil corresponding to that visit was scratched from the square to reveal the condom type allocation for the next condom-use period. Staff in the South African and Chinese trial sites were trained in use and care of the card, and on completion of the study completed a questionnaire on their experience of use. RESULTS: Research staff in both countries found the card easy to use and those who had previously used the sequentially numbered, opaque, sealed envelopes (SNOSE) system for random allocation reported the scratch card easier to use. Research staff most commonly used a coin to remove the foil square and some used their fingernails. In both South Africa and China, no errors in allocation sequence were found during study monitoring. LIMITATIONS: Scratch card system of allocation cannot be printed in-house. CONCLUSIONS: This novel, effective method of concealment for a crossover random allocation was well liked by study staff. The most important advantage of this method is the ability to conceal consecutive allocations of a crossover design using a single card, thus eliminating the need for multiple envelopes per participant. While we used this method in a clinical trial of FCs, it could be employed in a range of other clinical trials and other randomized studies.

New female condoms in the pipeline.

Male and female condoms are currently the only effective dual protection methods against unintended pregnancy and transmission of STIs and HIV. In recent years, advocacy and support to female condom (FC) programmes and increased distribution have played a significant role in highlighting to donors, policy-makers and programme managers the importance of FCs as essential tools for dual prevention. Further, the emergence of new FC products, differing in design and materials, has the potential to lower cost and improve acceptability. There are hurdles in developing new FC products, by far the greatest being the clinical studies required for regulatory purposes. However, several new designs are now available in selected countries and some are progressing through the final stages of regulatory approval, after which they will be more widely available. The new FC designs, which may also be more affordable, will increase options and choice for couples who want to use FCs as their prevention method. Here, we review the FC products that are available now and those still in development which are expected to be available within the next two to five years.

Acceptability of a non-woven device for vaginal drug delivery of microbicides or other active agents.

Vaginal microbicides could reduce incidence of HIV. However, the current method of delivering gel formulations (standard applicator) can result in acceptability concerns/issues. This study evaluated the concept of using a non-woven textile material (modified tampon) for vaginal drug delivery. The study was nested within a Phase I randomized safety trial of lime juice concentrations used intra-vaginally. Of 47 women completing the safety trial, 16 were interviewed about their experiences. Overall, women found the concept of non-woven materials for vaginal drug delivery acceptable for use in delivering yeast medications (13 of 16) and STI/HIV preventives (10 of 16).

Standardized definitions of failure modes for female condoms.

Definitions of male condom failure modes are now well documented, and failure events are usually reported as the proportion of the total number of condoms used and the proportion of men/couples who experience an event. The lack of standardized definitions for female condom (FC) failure has led to variability in reporting and hence difficulties in making comparisons across studies. As a result, the World Health Organization convened a technical review committee meeting in January 2006 through which the members compiled and agreed to a standard list of terms and definitions for each of the failure modes. These failure modes apply to FCs currently marketed or in advanced stages of clinical testing. They were designed to assist in the review and comparative assessment of different FCs.

Performance of the Reality polyurethane female condom and a synthetic latex prototype: a randomized crossover trial among South African women.

OBJECTIVE: This multisite, randomized, crossover trial comparing the performance of the Reality female condom (FC1) with a new synthetic latex prototype (FC2) was conducted in Durban, South Africa. METHOD: In total, 276 women were enrolled and 201 women completed the study. Altogether, 1910 FC1 condoms and 1,881 FC2 condoms were used. RESULTS: Total breakage was 0.73% in FC1 and 0.85% in FC2 (95% confidence interval, -0.64 to 0.87). The number of clinical breakages (those that could result in a pregnancy or sexually transmitted infection) was similar for each condom type (FC1, n=9; FC2, n=8). Incorrect penetration (penis between condom and vaginal wall) was 1.26% and 0.64% for FC1 and FC2, respectively. Outer ring displacements (outer ring pushed into the vagina partially or fully) were comparable for both condoms (FC1, 3.14%; FC2, 2.98%). Slippage (condom came out of the vagina) was rare and reported in 0.37% or less of devices used. Total clinical failure was 5.24% in FC1 and 4.3% in FC2. CONCLUSION: The FC1 and FC2 performed comparably within this trial.

The female condom learning curve: patterns of female condom failure over 20 uses.

BACKGROUND: Male and female condom (FC) functional performance failure declines with user experience. With the recent availability of a wider range of FCs, it is important to know if women with experience in using one type of FC are more proficient in using another type, even if the FC design is quite different. STUDY DESIGN: A randomized, noninferiority crossover clinical trial assessed the function of four FCs (FC2, Woman's Condom, Cupid and VA w.o.w) among 300 women in Durban, South Africa. FC functional failure (breakage, slippage, invagination and misdirection) by condom type and use period was investigated in women using five FCs of each type (20 FC uses in total). RESULTS: Of the 5364 condoms used during intercourse by 272 women, 200 clinical failures occurred in 195 condoms (190 condoms had one failure, and 5 had two failures). Total clinical failure was comparable across FC types. Of the 195 condoms in which failures occurred, the number of failures in the first condom use period was 103 (7.7%), decreasing to 43 events (3.2%) in the second, 33 (2.5%) in the third and 16 (1.2%) in the fourth. Only 2 failures were reported in the 20th use of an FC compared to 29 in the first use, irrespective of condom type. CONCLUSIONS: FC failure rates decreased markedly after use of the first five condoms regardless of FC type and continued to fall across the next three use periods. IMPLICATIONS: FC failure rates decrease over 20 uses, regardless of FC condom type used. The decrease is higher at the beginning of use, indicating that improvement is greatest after the first five uses.

Acceptability of a nipple shield delivery system administering antiviral agents to prevent mother-to-child transmission of HIV through breastfeeding.

BACKGROUND: Breastfeeding is a route of mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV). The World Health Organization recommends antiretroviral (ARV) prophylaxis as the best method to prevent mother-to-child transmission of HIV (PMTCT) during breastfeeding. The nipple shield delivery system (NSDS) is being developed as an accessible method to deliver ARVs to infants and PMTCT during breastfeeding. The NSDS can potentially circumvent hygiene and storage issues in delivering drugs to infants in low-resource settings. OBJECTIVES: The primary objective was to determine acceptability of the NSDS for PMTCT in Kenya. Secondary objectives included assessing mothers' understanding of MTCT and identifying cultural and implementation issues that might affect NSDS acceptability. METHODS: Eleven focus group discussions were conducted, each group consisting of 7 to 12 participants. Seven focus group discussions consisted of HIV-positive mothers, 2 included grandmothers/mothers-in-law, and 2 included fathers/husbands. Ten in-depth interviews were also conducted with individual maternal/child health care providers. Topics included infant feeding and HIV stigma, as well as safety, effectiveness, and feasibility of the NSDS. Device prototypes were used in discussions. RESULTS: Participants felt that the NSDS could be trusted if validated scientifically and promoted by health care professionals. HIV-related stigma, access, efficacy, and hygiene were identified as important considerations for acceptance. CONCLUSION: The NSDS is a potentially acceptable method of PMTCT during breastfeeding. Further studies are needed to confirm acceptability, safety, and efficacy. For NSDS adoption to PMTCT, strategies will need to be developed to minimize HIV-related stigma and to ensure that continuous hygiene of the device is maintained.

Performance and safety of the second-generation female condom (FC2) versus the Woman's, the VA worn-of-women, and the Cupid female condoms: a randomised controlled non-inferiority crossover trial.

BACKGROUND: New designs of female condom have been developed to reduce costs and improve acceptability. To secure regulatory approvals, clinical studies are needed to verify performance. We aimed to assess the functional performance and safety of three new condom types-the Woman's Condom, the VA worn-of-women (wow) Condom Feminine, and the Cupid female condom-against the existing second-generation female condom (FC2). METHODS: We did a randomised controlled, non-inferiority, four-period crossover trial at three sites in Shanghai, China, and one site in Durban, South Africa, between May 1, 2011, and Jan 31, 2012. Participants aged 18-45 years who were sexually active, monogamous, not pregnant, and not sex workers, were eligible for inclusion if they were literate, had no known allergies to the study products; used a reliable, non-barrier method of contraception, and had no visible or reported sexually transmitted infections. We used a computer-generated randomisation sequence with a Williams square design of size four to assign patients (1:1:1:1) to the FC2 control device, or the Woman's, VA wow, or Cupid condoms, with 12 potential allocations. Randomisation was stratified by site. Participants were not masked to condom type, but allocation was concealed from study investigators. The primary non-inferiority endpoints were total clinical failure and total female condom failure, with a non-inferiority margin of 3%. Women were asked to use five of each condom type and were interviewed after use of each type. We also assessed safety data for each type. We did both per-protocol and intention-to-treat analyses. We calculated frequencies and percentages for each failure event and estimated differences in performance with a generalised estimating equation model. This study is registered, number DOH-27-0113-4271. FINDINGS: 616 women were assessed for eligibility, of whom 600 were randomly assigned to condom-type order (30, 120, and 150 women in the three sites in China, and 300 women in the site in South Africa). 572 women completed follow-up, with at least one condom of each type. Total female condom failure was 3·43% for FC2, 3·85% for the Woman's Condom (difference 0·42%, 90% CI -1·42 to 2·26), 3·02% for VA wow (-0·42%, -1·86 to 1·32), and 4·52% for Cupid (1·09%, -0·60 to 2·78); total clinical failure was 2·88%, 3·05% (0·17%, -1·48 to 1·81), 2·49% (-0·25%, -1·75 to 1·26), and 3·87% (0·99%, -0·55 to 2·52), respectively. Only two (<1%) participants, in South Africa, reported serious adverse events, unrelated to use of the study products. INTERPRETATION: Non-inferiority was shown for all condom failure events for the three new devices versus the FC2, within the predefined margin. FUNDING: Universal Access to Female Condoms (UAFC).

Practice makes perfect: reduction in female condom failures and user problems with short-term experience in a randomized trial.

BACKGROUND: Female condom (FC) failure (breakage, slippage, invagination and misdirection) declines with user experience. Participants in FC performance trials are commonly novice users, and failure rates may be inflated related to inexperience. STUDY DESIGN: This was a randomized, crossover study assessing preference, safety, acceptability and function of three new FCs (WC, FC2 and V-Amour) among 170 women in Durban, South Africa. FC failure by condom type use period was investigated in women using five FCs of each type. RESULTS: Of the 2411 condoms used during intercourse, 96 failures (breakage, slippage, invagination and misdirection) occurred in 86 condoms (77 condoms had one failure, 8 condoms had two failures, and 1 condom had three failures). Total clinical failure was comparable across FC types. The number of failures in the first condom use period was 58 (7.0%), and this decreased to 21 events (2.6%) in the second and, finally, 17 (2.1%) in the last condom use period. No failures were reported in the last use of the FC in the final condom use period. CONCLUSIONS: FC failure rates decreased markedly after use of the first five condoms, regardless of FC type, and stabilized in the second and third use periods. Consideration should be given to the number of condoms used in trials to ensure that failure rates are not inflated by limiting the numbers of condoms used by novice users.

Female condom technology: new products and regulatory issues.

Like male condoms, female condoms (FCs) provide protection against unplanned pregnancy and most sexually transmitted infections including HIV. The first FC made by the Female Health Company was approved by the US Food and Drug Administration (USFDA) in 1993. Since 2000, several different types of FCs have become available or are in development to lower the cost and/or improve acceptability. Although similar in function, new FCs often differ in design and materials. Classified as Class III medical devices by the USFDA, FCs have a regulatory process that is more complex than that for male condoms. This, coupled with the lack of an international standard to verify the quality of new devices, has hindered new products gaining regulatory approvals and entering the market. We review the existing regulatory pathway for FCs, the progress made in developing standards specifically for FCs and the FCs available now or in development, including their current status regarding approval.

Three new female condoms: which do South-African women prefer?

BACKGROUND: The widespread distribution of female condoms (FCs) in developing countries has been hindered by high unit cost, making new less expensive devices a priority for donor agencies. STUDY DESIGN: Randomized, crossover study assessing product preference, safety, acceptability and function of three new FCs (PATH Woman's Condom, FC2 and V-Amour) among 170 women in Durban, South Africa. A subsequent "simulated market" study provided participants with free choice of FCs and assessed condom uptake over 3 months. RESULTS: Of the 160 women who used at least one FC of each type, 47.5% preferred the PATH Woman's Condom (WC), 35.6% preferred FC2 and 16.3% preferred V-Amour (p<.001). Women rated the WC better than FC2 and V-Amour for appearance, ease of use and overall fit and better than V-Amour for feel. WC was rated worse than FC2 and V-Amour for lubrication volume. The simulated market demonstrated similar preferences. Total clinical failure rates (i.e., the types of failures that could result in pregnancy or STI) were low (<4%), regardless of condom type. CONCLUSIONS: Three new FC types functioned similarly and were generally acceptable. Most participants preferred WC and FC2 over V-Amour, and WC was preferred over FC2 in several acceptability measures.

The effects of condom choice on self-reported condom use among men in Ghana, Kenya and South Africa: a randomized trial.

BACKGROUND: Male condoms are readily available and affordable in many settings, but risky sexual acts still go unprotected. STUDY DESIGN: This unblinded randomized trial, conducted in Ghana, Kenya and South Africa, was designed to assess the impact of providing a choice of condoms on self-reported use and uptake over 6 months. RESULTS: We enrolled 1,274 men. The mean subject-specific proportion of protected acts with all partners increased from baseline to 6 months by 0.07 in the control group compared to 0.03 in the choice group (p=.025). The observed results were largely consistent across all three countries. In the choice group, men clearly preferred one condom type over the others, and this preference was consistent across all three countries. CONCLUSIONS: Providing one type of male condom in public sector programs appears justified. Programs should not focus on the number of brands available, but should encourage effective promotion and consistent and correct use of available brands.

Perspectives related to the potential use of vaginal microbicides among drug-involved women: focus groups in three cities in the United States and Puerto Rico.

HIV transmission through heterosexual contact remains the greatest risk factor for women globally. Topical microbicides applied intravaginally may offer a female-initiated HIV prevention option for many who are unable or unwilling to use male condoms or who would want additional protection. This article presents results of focus groups in Bridgeport, Connecticut, Providence, Rhode Island, and San Juan, Puerto Rico, with women who use crack or heroin or have male partners who inject illegal drugs. Participants revealed motivation for and openness to using microbicides effective against HIV should they become available. Additional lubrication during intercourse was one of several expected positive features of microbicides; women saw lubrication as a means of enhancing pleasure and reducing condom irritation and breakage while also protecting them from infection. Conversely, some women feared that their male partners would interpret excessive lubrication as an indication of infection, improper hygiene, or evidence of sex with another man. Focus groups also provided insight into how aspects of different women's sexual lives, including partner type, might influence the issues that would concern them if and when they tried out new microbicidal products in the future.