A Temperature-Monitoring Vaginal Ring for Measuring Adherence

Peter Boyd,Susan M Fetherston,Sandeep Kumar,Manjula Narasimhan,Nathalie Dereuddre-Bosquet,Ásgeir Bjarnason,R Karl Malcolm,Delphine Desjardins,Berglind Helgadóttir,Roger Le-Grand

doi:10.1371/journal.pone.0125682

Abstract

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

Highlights

Vaginal rings containing embedded temperature loggers may be useful in the assessment of product adherence in late-stage clinical trials
It has long been assumed that use of sustained or controlled release delivery systems for vaginal administration of microbicides to prevent infection with human immunodeficiency virus (HIV) will lead to increased microbicide product adherence, acceptability and efficacy compared with more conventional, coitally-dependent, vaginal formulations [1,2,3,4]
The first convincing evidence in support of the vaginal microbicide concept came from the CAPRISA 004 trial in which a tenofovir gel reduced HIV acquisition by an estimated 39% [10,11,12]

Summary

Introduction

It has long been assumed that use of sustained or controlled release delivery systems for vaginal administration of microbicides to prevent infection with human immunodeficiency virus (HIV) will lead to increased microbicide product adherence, acceptability and efficacy compared with more conventional, coitally-dependent, vaginal formulations [1,2,3,4]. Based on adherence data from other clinical indications [5,6,7], including hormonal contraception for which long-acting depot injections, sub-dermal implants, transdermal patches and vaginal rings are available [8,9], the case for sustained/controlled release of HIV microbicides is generally well made and widely accepted. Considered to be proportional to core body temperature as in the case for rectal temperature measurement, the recording of vaginal temperature offers an alternative and interesting biomarker option for monitoring adherence to microbicide-releasing vaginal rings. Recorded temperature deviations away from the limited diurnal range observed within the vaginal vault of a patient could be used as indicative evidence that a ring device has been removed and left exposed to the much more varied environmental temperature range

Methods

Results

Conclusion