Dataset Information

A temperature-monitoring vaginal ring for measuring adherence.

ABSTRACT:

Background

Product adherence is a pivotal issue in the development of effective vaginal microbicides to reduce sexual transmission of HIV. To date, the six Phase III studies of vaginal gel products have relied primarily on self-reporting of adherence. Accurate and reliable methods for monitoring user adherence to microbicide-releasing vaginal rings have yet to be established.

Methods

A silicone elastomer vaginal ring prototype containing an embedded, miniature temperature logger has been developed and tested in vitro and in cynomolgus macaques for its potential to continuously monitor environmental temperature and accurately determine episodes of ring insertion and removal.

Results

In vitro studies demonstrated that DST nano-T temperature loggers encapsulated in medical grade silicone elastomer were able to accurately and continuously measure environmental temperature. The devices responded quickly to temperature changes despite being embedded in different thickness of silicone elastomer. Prototype vaginal rings measured higher temperatures compared with a subcutaneously implanted device, showed high sensitivity to diurnal fluctuations in vaginal temperature, and accurately detected periods of ring removal when tested in macaques.

Conclusions

Vaginal rings containing embedded temperature loggers may be useful in the assessment of product adherence in late-stage clinical trials.

SUBMITTER: Boyd P

PROVIDER: S-EPMC4429109 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

A temperature-monitoring vaginal ring for measuring adherence.

Boyd Peter P Desjardins Delphine D Kumar Sandeep S Fetherston Susan M SM Le-Grand Roger R Dereuddre-Bosquet Nathalie N Helgadóttir Berglind B Bjarnason Ásgeir Á Narasimhan Manjula M Malcolm R Karl RK

PloS one 20150512 5

<h4>Background</h4>Product adherence is a pivotal issue in the development of effective vaginal microbicides to reduce sexual transmission of HIV. To date, the six Phase III studies of vaginal gel products have relied primarily on self-reporting of adherence. Accurate and reliable methods for monitoring user adherence to microbicide-releasing vaginal rings have yet to be established.<h4>Methods</h4>A silicone elastomer vaginal ring prototype containing an embedded, miniature temperature logger h ...[more]

PMID: 25965956

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Project description:Although vaginal microbicides for HIV prevention are designed to be female-initiated, male partner influence has been identified as one of the most significant factors impacting women's willingness and ability to use them. As a result, research teams have sought to increase male partner involvement by encouraging disclosure of product use to male partners, promoting male partner engagement in the study through attendance at the study clinic, and helping women to garner male partner support for product use. This paper aims to assess the impact of these three elements of male partner involvement on women's adherence to the dapivirine vaginal ring during MTN-020/ASPIRE, a phase III randomized placebo-controlled clinical trial involving 2629 women in Malawi, South Africa, Uganda, and Zimbabwe. During the study, 64-80% of participants reported disclosure of ring use at each quarterly visit, and 13% reported that their partners had attended the study clinic at some point during the study. At study exit, 66% reported that their partner was supportive, 18% unsupportive, and 17% were unsure. After adjusting for age, site and time in study, women were more likely to have low ring adherence if they had an unsupportive male partner (aRR 1.29, 95% CI 1.03-1.62). Neither disclosure nor clinic attendance directly predicted ring adherence, but disclosure increased the probability of having a supportive partner (aRRR 24.17, 95% CI 16.38-35.66) or an unsupportive partner (aRRR 4.10, 95% CI 2.70-6.24), relative to an unknown level of partner support. Women were also more likely to have a supportive partner if their partner had attended the clinic (aRRR 3.77, 95% CI 1.36-10.42). This study suggests that although the vaginal ring is relatively discreet, lack of support from male partners remains a relevant barrier to use. Though both disclosure and clinic attendance may increase partner support, disclosure may also increase partner opposition. Interventions to reduce male partner opposition are needed to maximize the potential impact of the ring and other PrEP products for HIV prevention.

Project description:BACKGROUND:This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women. OBJECTIVES:The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa. METHODS:280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports. RESULTS:No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. CONCLUSIONS:The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women. TRIAL REGISTRATION:ClinicalTrials.gov NCT01071174.

Project description:This analysis compares self-reports of product use with objective measures of non-adherence-quarterly plasma dapivirine levels and monthly residual dapivirine (DPV) levels in used rings-in MTN-020/ASPIRE, a phase 3 trial of a monthly DPV vaginal ring among women aged 18-45 years in Malawi, South Africa, Uganda and Zimbabwe. For participants on active product (N?=?1211) we assessed self-reported monthly non-adherence, as measured by (1) whether the ring was ever out, and out for???12 h in the previous month and, (2) by a self-rating scale assessing ability to keep the vaginal ring inserted, and compared the self-reports to two biomarkers of non-use separately and as a composite measure. For this analysis, a plasma DPV value???95 pg/ml and residual ring???23.5 mg were used to classify non-adherence (i.e. the ring never being in the vagina the previous month). Compared to self-reports, non-adherence was found to be substantially higher for the composite measure as well as its two components, an indication that ring removal was likely underreported in the trial. The discrepancy between the self-report measure of ring outage and the composite indicator was greater for those aged 18-21 than for those older, evidence that younger women are more likely to underreport non-adherence. Despite underreporting of non-adherence, self-reports of the ring never being out were significant in predicting the composite objective measure. Furthermore, the association between the self-rating scale and the objective measure was in the expected direction and significant, although 11% of those 18-21 and 7% of those 22+?who rated their ability to keep the ring inserted as good, very good or excellent in the 4 weeks prior to exit were considered non-adherent according to the objective measure. This analysis indicates that while self-reports are significantly associated with objective measures of adherence in the ASPIRE trial, they were inflated-more so by those younger-and therefore may have limited utility identifying those who have challenges using products as directed. ClinicalTrials.gov number NCT01617096.

Project description:We investigated the presence, density and bacterial composition of contraceptive vaginal ring biomass and its association with the vaginal microbiome. Of 415 rings worn by 120 Rwandese women for three weeks, the biomass density was assessed with crystal violet and the bacterial composition of biomass eluates was assessed with quantitative polymerase chain reaction (qPCR). The biomass was visualised after fluorescence in situ hybridisation (FISH) and with scanning electron microscopy (SEM). The vaginal microbiome was assessed with Nugent scoring and vaginal biofilm was visualised after FISH. All vaginal rings were covered with biomass (mean optical density (OD) of 3.36; standard deviation (SD) 0.64). Lactobacilli were present on 93% of the rings, Gardnerella vaginalis on 57%, and Atopobium vaginae on 37%. The ring biomass density was associated with the concentration of A. vaginae (OD +0.03; 95% confidence interval (CI) 0.01-0.05 for one log increase; p = 0.002) and of G. vaginalis (OD +0.03; (95% CI 0.01-0.05; p = 0.013). The density also correlated with Nugent score: rings worn by women with a BV Nugent score (mean OD +0.26), and intermediate score (mean OD +0.09) had a denser biomass compared to rings worn by participants with a normal score (p = 0.002). Furthermore, presence of vaginal biofilm containing G. vaginalis (p = 0.001) and A. vaginae (p = 0.005) correlated with a denser ring biomass (mean OD +0.24 and +0.22 respectively). With SEM we observed either a loose network of elongated bacteria or a dense biofilm. We found a correlation between vaginal dysbiosis and the density and composition of the ring biomass, and further research is needed to determine if these relationships are causal. As multipurpose vaginal rings to prevent pregnancy, HIV, and other sexually transmitted diseases are being developed, the potential impact of ring biomass on the vaginal microbiota and the release of active pharmaceutical ingredients should be researched in depth.

Dataset Information

A temperature-monitoring vaginal ring for measuring adherence.

Background

Methods

Results

Conclusions

Publications

A temperature-monitoring vaginal ring for measuring adherence.

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