An intravaginal ring for real-time evaluation of adherence to therapy

Two recent Phase III clinical trials to investigate an intravaginal ring for preventing HIV infection demonstrated that adherence to prescribed device use was a primary driver of efficacy. Surrogate methods for determining adherence in the studies were limited in their inability to monitor temporal patterns of use and allow deconvolution of the effects of adherence and device efficacy on HIV infection rates. To address this issue, we have developed functionality in an intravaginal ring to continuously monitor when the device is being used and maintain a log of adherence that can be accessed by clinicians after it is removed. An electronic module fabricated with common, inexpensive electronic components was encapsulated in a silicone intravaginal ring. The device uses temperature as a surrogate measure of periods of device insertion and removal, and stores a record of the data for subsequent retrieval. The adherence-monitoring intravaginal ring accurately recorded the device status over 33 simulated IN-OUT cycles and more than 1000 measurement cycles in vitro. Following initial in vitro testing in a temperature-controlled chamber, the device was evaluated in vivo in sheep using a predetermined insertion/removal pattern to simulate intravaginal ring use. After insertion into the vaginal cavity of a sheep, the logged data correctly indicated the device status over 29 hours of continuous measurement including three cycles of insertion and removal. The device described here is a promising, low-cost method for real-time adherence assessment in clinical trials involving medicated intravaginal rings or other intravaginal devices.