Dataset Information

Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE.

ABSTRACT: 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.

SUBMITTER: Mensch BS

PROVIDER: S-EPMC6374159 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE.

Mensch Barbara S BS Richardson Barbra A BA Husnik Marla M Brown Elizabeth R ER Kiweewa Flavia Matovu FM Mayo Ashley J AJ Baeten Jared M JM Palanee-Phillips Thesla T van der Straten Ariane A

AIDS and behavior 20190201 2

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 pre ...[more]

PMID: 30218318

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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:Results of recent microbicide and pre-exposure prophylaxis clinical trials have shown adherence to be a significant challenge with new HIV prevention technologies. As the vaginal ring containing dapivirine moves into two open label follow-on studies (HOPE/MTN-025 and DREAM) and other antiretroviral-based and multi-purpose prevention technology ring products advance through the development pipeline, there is a need for more accurate and reliable measures of adherence to microbicide ring products. We previously conducted a comprehensive landscape analysis to identify new technologies that could be applied to adherence measurement of vaginal rings containing antiretrovirals. To explore attitudes and perceptions towards the approaches that we identified, we conducted a survey of stakeholders with experience and expertise in microbicide and HIV prevention clinical trials. From May to July 2015 an electronic survey was distributed via email to 894 stakeholders; a total of 206 eligible individuals responded to at least one question and were included in the data analysis. Survey respondents were presented with various objective measures and asked about their perceived acceptability to trial participants, feasibility of implementation by study staff, usefulness for measuring adherence and ethical concerns. Methods that require no additional input from the participant and require no modifications to the existing ring product (i.e., measurement of residual drug or excipient, or a vaginal analyte that enters the ring) were viewed as being more acceptable to trial participants and more feasible to implement in the field. Respondents saw value in using objective measures to provide real-time feedback on adherence. However, approaches that involve unannounced home visits for sample collection or spot checks of ring use, which could provide significant value to adherence feedback efforts, were met with skepticism. Additional research on the acceptability of these methods to potential trial participants and trial staff is recommended.

Project description:BackgroundObjectively measured reduction in lumbar posterior-to-anterior (PA) stiffness is associated with pain relief in some, but not all persons with low back pain. Unfortunately, these measurements can be time consuming to perform. In comparison, the Lumbar Spine Instability Questionnaire (LSIQ) is intended to measure spinal instability and the Lumbar Spine Disability Index (LSDI) is created for self-reporting functional disability due to increased spinal stiffness. Given the above, the aim of this study is to compare measures of the LSIQ and LSDI with objective measures of lumbar PA stiffness as measured by a mechanical device, Vertetrack (VT), in patients with persistent non-specific low back pain (nsLBP).MethodsTwenty-nine patients with nsLBP completed the LSIQ and LSDI at baseline and after two weeks. On these same occasions, PA spinal stiffness was measured using the VT. Between measurements, patients received four sessions of spinal manipulation. The resulting data was analyzed to determine the correlation between the self-report and objective measures of stiffness at both time points. Further, the patients were categorized into responders and non-responders based on pre-established cut points depending on values from the VT and compared those to self-report measures in order to determine whether the LSIQ and the LSDI were sensitive to change.ResultsTwenty-nine participants completed the study. Measures from the LSIQ and LSDI correlated poorly with objectively measured lumbar PA stiffness at baseline and also with the change scores. The change in objectively measured lumbar PA stiffness following spinal manipulation did not differ between those who improved, and those who did not improve according to the pre-specified cut-points. Finally, a reduction in lumbar PA stiffness following intervention was not associated with improvement in LSIQ and LSDI outcomes.ConclusionsThe current data indicate that the LSIQ and LSDI questionnaires do not correlate with measures obtained objectively by VT. Our results suggest that these objective and self- reported measures represent different domains and as such, cannot stand in place of one another.

Project description:BACKGROUND:Adherence is critical for successful topical, vaginally delivered anti-retroviral (ARV)-based HIV pre-exposure prophylaxis (PrEP). Quantitating systemic or tissue ARV levels through LC-MS/MS is currently viewed as the most reliable measure of adherence. However, for placebo-controlled trials, this is a high cost analysis that measures adherence only in the drug treatment group. A desirable marker of adherence is one that is measured in both placebo and drug treatment groups using a simple on-site clinical laboratory test, which allows necessary interventions for supporting participant adherence. Our objective was to develop adherence markers for four vaginal placebo products currently used as microbicide delivery systems: gel, film, insert, and intravaginal ring. Excipient and spectroscopy-based approaches were used for preclinical development of the placebo markers and subsequently validated by the CONRAD 135 study. The study collected vaginal swabs collected each day for 1 week post vaginal application of gel, film, or insert in the clinic with or without sex. Intravaginal rings were collected after 1 day, 7, and 30 days of use. RESULTS:Placebo gel, film, and insert in vaginal swabs were successfully detected by specific excipient colorimetric or probe-based assays for hydroxyethylcellulose, glycerin, and sorbitol respectively, as well as spectroscopy-based prediction models. The range of detection for gel, film, and insert in swabs collected up to 16 h post vaginal application was 70-100% of the total swabs per time point, with some markers showing potential for longer duration. Decreasing residual glycerin levels and increasing bioanalyte penetration of vaginally used intravaginal rings showed significant changes between 1 and 30 days of use. CONCLUSIONS:We demonstrated clinical proof-of-concept that adherence markers for placebo product can be measured using simple, lower cost approaches. Measuring adherence in both placebo and drug arms of a HIV PrEP study would better inform future trial designs.

Dataset Information

Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE.

Publications

Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE.

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