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Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors. Ex vivo assessments showed that the MAPs delivered an average of 176 ± 60.9 μg of NGMN per MAP into excised neonatal porcine skin, representing 15.3 ± 5.3% of the loaded drug. In vivo pharmacokinetic analysis in Sprague Dawley rats demonstrated a Tmax of 4 h and a Cmax of 67.4 ± 20.1 ng/mL for the MAP-treated group, compared to a Tmax of 1 h and a Cmax of 700 ± 138 ng/mL for the intramuscular (IM) injection group, with a relative bioavailability of approximately 10% for the MAPs. The MAP-treated rats maintained plasma levels sufficient for therapeutic effects for up to 7 days after a single application. These results indicate the potential of NGMN-loaded dissolving bilayer MAPs, with further development focused on extending the release duration and improving bioavailability for prolonged contraceptive effects. [ABSTRACT FROM AUTHOR]

To estimate contraceptive efficacy, safety, acceptability, and fit of a single-size diaphragm used with contraceptive gel.We conducted a multicenter trial in which 450 couples used the single-size diaphragm, 300 randomized to acid-buffering gel and 150 to nonoxynol-9, for at least 190 days and six menstrual cycles. Visits were at enrollment and after menstrual cycles 1, 3, and 6. Study outcomes included pregnancy probability, safety, acceptability, and fit. Pregnancy and safety were compared with an historical control group who used a standard diaphragm with these gels.Most (439/450 [98%]) women could be fitted with the single-size diaphragm. A total of 421 of 450 (94%) provided follow-up. The 35 study pregnancies yielded 6-month Kaplan-Meier cumulative typical use pregnancy probabilities per 100 women with 95% confidence intervals (CIs) of 10.4 (6.9-14.0) for all users and 9.6 (5.5-13.6) and 12.5 (5.4-19.5) with acid-buffering gel and nonoxynol-9, respectively. Historical control analysis yielded a propensity score-adjusted estimate of this pregnancy probability for the single-size diaphragm of 11.3 compared with 10.7 per 100 women for the standard diaphragm ([rounded] difference 0.7, 95% CI -3.6 to 4.9). Approximately half (51%) reported at least one urogenital event but compared favorably to the standard diaphragm in historical control analysis. Most (282/342 [82%]) liked the diaphragm. Results suggest that if provided by a clinician, 94% (95% CI 92-96%) could insert, correctly position, and remove the diaphragm.The single-size diaphragm was safe, as effective as a standard diaphragm, and acceptable when used with contraceptive gel.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00578877.

Introduction: A number of antiretroviral HIV prevention products are efficacious in preventing HIV infection. However, the sexual and reproductive health needs of many women extend beyond HIV prevention, and research is ongoing to develop multi-purpose prevention technologies (MPTs) that offer dual HIV and pregnancy protection. We do not yet know if these products will be an efficient use of constrained health resources. In this paper, we estimate the cost-effectiveness of combinations of candidate multi-purpose prevention technologies (MPTs), in South Africa among general population women and female sex workers (FSWs). Methods: We combined a cost model with a static model of product impact based on incidence data in South Africa to estimate the cost-effectiveness of five candidate co-formulated or co-provided MPTs: oral PrEP, intravaginal ring, injectable ARV, microbicide gel and SILCS diaphragm used in concert with gel. We accounted for the preferences of end-users by predicting uptake using a discrete choice experiment (DCE). Product availability and protection were systematically varied in five potential rollout scenarios. The impact model estimated the number of infections averted through decreased incidence due to product use over one year. The comparator for each scenario was current levels of male condom use, while a health system perspective was used to estimate discounted lifetime treatment costs averted per HIV infection. Product benefit was estimated in disability-adjusted life years (DALYs) averted. Benefits from contraception were incorporated through adjusting the uptake of these products based on the DCE and through estimating the costs averted from avoiding unwanted pregnancies. We explore the additional impact of STI protection through increased uptake in a sensitivity analysis. Results: At central incidence rates, all single- and multi-purpose scenarios modelled were cost-effective among FSWs and women aged 16 24, at a governmental willingness-to-pay threshold of $1175/DALY averted (range: $214 $810/DALY averted among non-dominant scenarios), however, none were cost-effective among women aged 25 49 (minimum $1706/DALY averted). The cost-effectiveness of products improved with additional protection from pregnancy. Estimates were sensitive to variation in incidence assumptions, but robust to other parameters. Conclusions: To the best of our knowledge, this is the first study to estimate the cost-effectiveness of a range of potential MPTs; suggesting that MPTs will be cost-effective among higher incidence FSWs or young women, but not among lower incidence older women. More work is needed to make attractive MPTs available to potential users who could use them effectively. Keywords: discrete choice experiments; HIV prevention; key populations; multi-purpose prevention; pre-exposure prophylaxis; South Africa, 1 | INTRODUCTION Over the past six years, clinical trials have shown that antiretroviral (ARV)-based pre-exposure prophylaxis (PrEP) can be efficacious in preventing the transmission of human immunodeficiency virus (HIV) [...]

Introduction: This study aimed to assess acceptability and preferences for the SILCS diaphragm for vaginal gel delivery compared to a prefilled applicator. Methods: A randomized crossover study among 115 women in South Africa, using both methods during five sex acts. Results: We found no significant differences in acceptability between the two products. Experience of gel leakage after sex was greater when inserted via applicator. More women were interested in SILCS/gel for multipurpose protection (68%) than in either SILCS alone (17%) or microbicide gel alone (14%). Conclusions: A SILCS gel delivery system for multipurpose prevention seems feasible and acceptable. [ABSTRACT FROM AUTHOR]

Background. The development of antiretroviral (ARV)-based prevention products has the potential to substantially change the HIV prevention landscape; yet, little is known about how appealing these products will be outside of clinical trials, as compared with the existing options. Methods. We conducted a discrete choice experiment (DCE) to measure preferences for 5 new products among 4 important populations in the HIV response: adult men and women in the general population (aged 18 to 49 y), adolescent girls (aged 16 to 17 y), and self-identifying female sex workers (aged 18 to 49 y). We interviewed 661 self-reported HIV-negative participants in peri-urban South Africa, who were asked to choose between 3 unique, hypothetical products over 10 choice sets. Data were analyzed using multinomial, latent class and mixed multinomial logit models. Results. HIV protection was the most important attribute to respondents; however, results indicate significant demand among all groups for multipurpose prevention products that offer protection from HIV infection, other STIs, and unwanted pregnancy. All groups demonstrated a strong preference for long-lasting injectable products. There was substantial heterogeneity in preferences within and across population groups. Limitations. Hypothetical DCE data may not mirror real-world choices, and products will have more attributes in reality than represented in choice tasks. Background data on participants, including sensitive areas of HIV status and condom use, was self-reported. Conclusions. These results suggest that stimulating demand for new HIV prevention products may require a more a nuanced approach than simply developing highly effective products. No single product is likely to be equally attractive or acceptable across different groups. This study strengthens the call for effective and attractive multipurpose prevention products to be deployed as part of a comprehensive combination prevention strategy. [ABSTRACT FROM AUTHOR]

Background The Woman's Condom, a secondgeneration female condom, is currently being manufactured in China by the Shanghai Dahua Medical Apparatus Company. The manufacturer plans to launch the product in China. Methods A survey and focus group discussions were conducted with 73 women and 57 men from nine potential user groups in the Shanghai area to explore, on the basis of visual inspection of the Woman's Condom and product information, their perceptions and attitudes toward the Woman's Condom and lubricant. The potential user groups were male and female university students, male and female collegeeducated young people, married women and men, migrant women and men, and women working in the entertainment industry. Results Female condoms were a new concept for almost all study participants. Women (49%) and men (51%) reported that the Woman's Condom would make "some" or a "great" difference in their lives. Participants reported interest in using the Woman's Condom for sexually transmitted infection (STI) (50%) or dual protection (43%) rather than for pregnancy prevention alone (33%). Findings highlighted comfort, partner approval and lubricant as possible concerns. Conclusions Product introduction activities should be oriented toward the most likely early adopter groups (i.e. university students, collegeeducated young people, migrant women and women working in the entertainment industry). Lack of interest in using the new device by married women/men and migrant men may indicate that they do not perceive a need for a dual protection product since they are already using a contraceptive method and/or do not perceive themselves at risk of STIs. [ABSTRACT FROM AUTHOR]

An abstract of the article "Introduction of the SILCS Diaphragm as a Multipurpose Technology in South Africa: Potential Users, Perceived Benefits, and Barriers to Use" by Cecilia Milford and colleagues is presented.

Abstract: Background: This study was conducted to compare the effectiveness of a new, single-size silicone contraceptive diaphragm used with either spermicide [2% nonoxynol-9 (N-9)] or lubricant in preventing sperm from penetrating midcycle cervical mucus. Study design: A crossover postcoital test (PCT) in healthy, sexually active women not at risk for pregnancy due to tubal occlusion was conducted. Couples had a baseline PCT without a device to verify normal fertility parameters. Qualified couples underwent up to two test cycles using the SILCS diaphragm with a metal spring. A subgroup of couples underwent a third test cycle with the SILCS polymer spring diaphragm used with N-9 gel. Results: Fifteen couples completed a baseline cycle and were randomized to order of study gel. Of these, 14 couples completed a baseline cycle and at least one test cycle, 12 couples completed a baseline cycle and two test cycles and 8 couples completed a third test cycle with the polymer spring prototype. Sperm was detected in the vaginal pool in all completed test cycles. The SILCS metal spring diaphragms used with N-9 gel reduced the average number of progressively motile sperm per high power field in the cervical mucus from a baseline of 12.5 to 0, while use of this device with lubricant reduced the number to 0.5. The SILCS polymer spring diaphragm used with N-9 performed the same as the metal spring used with N-9. Conclusion: The SILCS diaphragm used with N-9 gel performed well. It is likely that the SILCS diaphragm will give acceptable results in a contraceptive effectiveness study but that adjunctive use of a chemical barrier such as N-9 gel will be necessary for it to be most effective. [Copyright &y& Elsevier]

Contraceptive diaphragms offer a discreet method of pregnancy protection that women can use when needed with no side effects. Incorporating antiretroviral HIV microbicides into such devices may also provide protection against HIV infection. The paper gives a brief outline of the work being conducted by PATH, CONRAD and QUB on the development of a microbicide-releasing SILCS diaphragm. The design, engineering and manufacturing challenges that have been encountered will be discussed, as well as the potential impact such a device could have in the developing world.