Design aspects of vaginal applicators that influence acceptance among target users

Although sensory-guided product design is most traditionally used by food and beverage companies, the approach has widespread application for many other products, including pharmaceuticals and medical devices. Previously, our team used sensory methods to explore preclinical optimization of soft-gel vaginal microbicides. Past clinical trials suggest vaginal microbicides may be an effective means for women to protect themselves from HIV and other sexually transmitted infections, but these microbicides will not work if they are not used due to poor acceptability. Our prior work suggests properties like firmness, size, and shape all influence women’s willingness to try soft-gel vaginal suppositories. As product insertion is part of the overall experience of using vaginal microbicides, understanding the features of vaginal applicators that appeal to women, and incorporating these insights into vaginal drug delivery systems, may also improve user adherence. Despite widespread use of vaginal applicators, there is minimal public data on women’s perceptions of and preferences for physical applicator features. Other work suggests women want vaginal applicators that are single use, pre-filled, made of plastic, and easy to use, store, and discard. Applicator attributes that may be important to women, such as length, color, or visual appeal, have not been investigated previously. The objective of this research was to understand what physical applicator attributes are appealing to women. Here, 18 commercially available applicators were evaluated by a convenience sample of women (n = 102) for overall liking and perceptions of various attributes (perceived length and width, ease-of-grip, expected ease-of-use, expected comfort inside the body, visual appeal, color liking, and environmental friendliness). Preference mapping using both liking data and attribute data showed attributes such as color, visual appeal, ease of grip, expected ease of use, and expected comfort inside the body drove higher liking ratings for applicators, while perceived length negatively affected liking. In general, plastic tampon applicators contained more positive features and were better liked relative to a cardboard tampon applicator or applicators for insertion of medicated gels or suppositories. Incorporating more desirable features into applicators meant for insertion of vaginal microbicides or other vaginal medications may improve the user experience, and possibly user adherence.

Acceptability and feasibility of the CHARISMA counseling intervention to support women’s use of pre-exposure prophylaxis: results of a pilot study

Background Women may need or seek male partner approval to safely and consistently use oral antiretroviral pre-exposure prophylaxis (PrEP) or vaginal microbicides. We developed CHARISMA, a counseling intervention to support women’s relationships and their ability to consistently use HIV prevention products. Methods In a pilot study with 95 female participants in Johannesburg, South Africa, lay counselors implemented CHARISMA, assessing participants’ relationship(s) with their male partner(s) and barriers or facilitators to HIV prevention method use, and then providing tailored, interactive counseling. We conducted study participant surveys and clinic staff interviews to evaluate CHARISMA’s feasibility and acceptability. Results The CHARISMA pilot study indicates that a two-session relationship counseling intervention with 6-month follow-up to support women’s ability to safely and effectively use vaginal microbicides was generally acceptable and feasible. Most participants thought CHARISMA was relevant, helpful, and about the right length, and that it had a positive impact on their relationships with their partners and their product use. Staff estimated that the intervention took 1.5–2 h to implement at enrollment and 45 min to an hour for the month 1 visit. They thought that overall CHARISMA was generally feasible to implement. Conclusions Findings from this study suggest several lessons learned that may be relevant to others developing interventions supporting women’s use of oral PrEP or vaginal microbicides. The use of lay counselors instead of nurses to deliver counseling appeared to be successful, but the counselors experienced significant stress from hearing about participants’ traumatic experiences and required emotional support to avoid burnout. Although staff and participants felt that having multiple intervention sessions over time was valuable, a similar level of intensity may not be feasible in other settings. Further research is needed to determine an intervention delivery mode and follow-up period that optimally balances participant needs and clinic resources. Male engagement was a challenge, as it has been in previous studies of vaginal microbicides. Alternative strategies to reach men that do not require them to come to the clinic or rely on their female partners may be more effective.

Acceptability and Feasibility of the CHARISMA Counseling Intervention to Support Women’s Use of Pre-Exposure Prophylaxis

Background: Women may need or seek male partner approval to {Malow, 2000 #18}{Malow, 2000 #18}{Malow, 2000 #18}{Malow, 2000 #18}safely and consistently use oral antiretroviral pre-exposure prophylaxis (PrEP) or vaginal microbicides. We developed CHARISMA, a counseling intervention to support women’s relationships and their ability to consistently use HIV prevention products.Methods: In a pilot study with 95 female participants in Johannesburg, South Africa, lay counselors assessed participants’ relationship(s) with their male partner(s) and barriers or facilitators to HIV prevention method use, and then provided tailored, interactive counseling. We conducted study participant surveys and clinic staff interviews to evaluate CHARISMA’s feasibility and acceptability.Results: The CHARISMA pilot study indicates that a two-session relationship counseling intervention with 6-month follow-up to support women’s ability to safely and effectively use vaginal microbicides was generally acceptable and feasible. Most participants thought CHARISMA was relevant, helpful, and about the right length, and that it had a positive impact on their relationships with their partners and their product use. Staff stated that it was generally feasible to implement. Based on these promising preliminary findings, the project team is currently conducting a randomized controlled trial in which participants are receive either the standard of care for IPV screening and referral (control arm) or the CHARISMA intervention.Conclusions: Clinic staff felt strongly that the length and intensity of CHARISMA were necessary for participants to begin to trust the counselors enough to be open and honest about problems in their relationships, and to begin to overcome the normalization of intimate partner violence. The length and intensity of CHARISMA may not be feasible in some settings, but a shorter version of the intervention may not offer as much support as women and staff need. One possible approach to reduce the burden on clinic staff would be to self-administer the intervention through a computer rather than requiring a counselor. Lessons learned from the pilot study may be relevant to others developing interventions supporting women’s use of oral PrEP or vaginal microbicides.

Safety_and_Pharmacokinetics_of_Dapivirine_Delivery.7

Vaginal microbicides for the prevention of HIV transmission maybe an important option for protecting women from infection.Incorporation of dapivirine, a lead candidate nonnucleoside reversetranscriptase inhibitor, into intravaginal rings (IVRs) for sustainedmucosal delivery may increase microbicide product adherence andefficacy compared with conventional vaginal formulations. Twentyfourhealthy HIV-negative women 18–35 years of age were randomlyassigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR,or placebo IVR. Dapivirine concentrations were measured in plasmaand vaginal fluid samples collected at sequential time points over the33-day study period (28 days of IVR use, 5 days of follow-up). Safetywas assessed by pelvic/colposcopic examinations, clinical laboratorytests, and adverse events. Both IVR types were safe and well toleratedwith similar adverse events observed in the placebo and dapivirinegroups. Dapivirine from both IVR types was successfully distributedthroughout the lower genital tract at concentrations over 4 logs greaterthan the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximumconcentration (Cmax) and area under the concentration–time curve(AUC) values were significantly higher with the matrix than reservoirIVR. Mean plasma concentrations of dapivirine were ,2 ng/mL.These findings suggest that IVR delivery of microbicides is a viableoption meriting further study.Key Words: dapivirine, HIV, intravaginal ring, microbicide,pharmacokinetics, prevention

Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial a mixed-methods study,

THE GLOBAL HIV EPIDEMIC increasingly affectswomen.1 For most, the only risk factor for becominginfected is the behavior of their male sexualpartners.1 Condoms often are unacceptableand insufficiently used,2–4 gender-based powerimbalances can make them difficult to negotiate,4–7 and religious beliefs, fertility needs, fear ofimplied infidelity, and preferences for sex withouta barrier are challenges to their acceptabilityand use. Women-initiated HIV prevention methodsare urgently needed, making the developmentof vaginal microbicides that reduce the likelihoodof sexual transmission of HIV a majorpublic health priority.First-generation vaginal microbicides will mostlikely be topical gels inserted into the vagina withan applicator. A variety of microbicides is currentlyunder development, and six have enteredlate-stage clinical trials.8–12 Initial product acceptabilityhas been assessed in clinical trials,13–16 surveysof product attributes among potentialusers17,18 and their partners,19 and studies that useover-the-counter (OTC) surrogates or placebo gelwith presumed similar formulation and applicationcharacteristics as eventual products.20–23 Acceptabilityassessments in early clinical trials areespecially important because their findings can influencefurther development of the product.Here, we report on acceptability data amongwomen participating in a phase I trial of tenofovirgel, a candidate microbicide that inhibits HIV reversetranscriptase. Details of the trial are reportedelsewhere,24 as is acceptability amongmale partners of trial participants.25 This was thefirst human trial of a topical antiretroviral thatspecifically inhibits a necessary replication stepin the HIV life cycle. Interest in this approach toHIV prevention has increased in recent yearssince efficacy trials of a topical surfactant(nonoxynyl-9) and a nonspecific inhibitor of HIVbinding (cellulose sulfate) indicated that thesetwo types of compounds were not protective andpotentially increased HIV transmission in womenwho had frequent sexual exposures to HIV. Severallarger-scale, expanded safety and proof-ofconcepttrials of tenofovir gel are now underway,based in part on the safety, tolerability, and acceptabilityof this microbicide demonstrated inthe study described in this paper.

Carrageenan-Based Acyclovir Mucoadhesive Vaginal Tablets for Prevention of Genital Herpes

Women are the most affected by genital herpes, which is one of the most common sexually transmitted infections, affecting more than 400 million people worldwide. The application of vaginal microbicides could provide a safe method of protection. Acyclovir is a safe and effective medication for vaginal administration, and numerous benefits have been observed in the treatment of primary or recurrent lesions due to genital herpes. Vaginal tablets based on a combination of the polymers iota-carrageenan and hydroxypropyl methylcellulose were developed for the controlled release of acyclovir. Swelling, mucoadhesion and drug release studies were carried out in simulated vaginal fluid. The tablets, containing a combination of iota-carrageenan and hydroxypropyl methylcellulose, have an adequate uptake of the medium that allows them to develop the precise consistency and volume of gel for the controlled release of acyclovir. Its high mucoadhesive capacity also allows the formulation to remain in the vaginal area long enough to ensure the complete release of acyclovir. These promising formulations for the prevention of genital herpes deserve further evaluation.

Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention

HIV/AIDS stands as a global burden, and vaginal microbicides constitute a promising strategy for topical pre-exposure prophylaxis. Preceding the development of a microbicide containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), in silico and in vitro studies were performed to evaluate the physicochemical characteristics of both drugs, and to study their biophysical impact in lipid model systems. Results from these pre-formulation studies defined hydrogels as adequate vehicles to incorporate TDF-loaded liposomes and FTC. After studying interactions with mucin, zwitterionic liposomes with a mean diameter of 134 ± 13 nm, an encapsulation TDF efficiency of approximately 84%, and a transition temperature of 41 °C were selected. The chosen liposomal formulation was non-cytotoxic to HEC-1-A and CaSki cells, and was able to favor TDF permeation across polysulfone membranes (Jss = 9.9 μg·cm−2·h−1). After the incorporation of TDF-loaded liposomes and FTC in carbomer hydrogels, the drug release profile was sustained over time, reaching around 60% for both drugs within 3–6 h, and best fitting the Weibull model. Moreover, liposomal hydrogels featured pseudoplastic profiles that were deemed suitable for topical application. Overall, the proposed liposomal hydrogels may constitute a promising formulation for the vaginal co-delivery of TDF/FTC.