Biomarkers and biometric measures of adherence to use of ARV‐based vaginal rings

Abstract

IntroductionPoor adherence to product use has been observed in recent trials of antiretroviral (ARV)-based oral and vaginal gel HIV prevention products, resulting in an inability to determine product efficacy. The delivery of microbicides through vaginal rings is widely perceived as a way to achieve better adherence but vaginal rings do not eliminate the adherence challenges exhibited in clinical trials. Improved objective measures of adherence are needed as new ARV-based vaginal ring products enter the clinical trial stage.MethodsTo identify technologies that have potential future application for vaginal ring adherence measurement, a comprehensive literature search was conducted that covered a number of biomedical and public health databases, including PubMed, Embase, POPLINE and the Web of Science. Published patents and patent applications were also searched. Technical experts were also consulted to gather more information and help evaluate identified technologies. Approaches were evaluated as to feasibility of development and clinical trial implementation, cost and technical strength.ResultsNumerous approaches were identified through our landscape analysis and classified as either point measures or cumulative measures of vaginal ring adherence. Point measurements are those that give a measure of adherence at a particular point in time. Cumulative measures attempt to measure ring adherence over a period of time.DiscussionApproaches that require modifications to an existing ring product are at a significant disadvantage, as this will likely introduce additional regulatory barriers to the development process and increase manufacturing costs. From the point of view of clinical trial implementation, desirable attributes would be high acceptance by trial participants, and little or no additional time or training requirements on the part of participants or clinic staff. We have identified four promising approaches as being high priority for further development based on the following measurements: intracellular drug levels, drug levels in hair, the accumulation of a vaginal analyte that diffuses into the ring, and the depletion of an intrinsic ring constituent.ConclusionsWhile some approaches show significant promise over others, it is recommended that a strategy of using complementary biometric and behavioural approaches be adopted to best understand participants’ adherence to ARV-based ring products in clinical trials.

Comparing self-reported medication adherence measures with hair antiretroviral concentration among people living with HIV in Guangxi, China

“…Fourth, we chose to use hair antiretroviral concentration as a single criterion to test the validity of self-reported measures in this study. While hair antiretroviral concentration has been previously shown to be an excellent measure for long-term antiretroviral exposure [7,48,49], future research should employ multiple criteria such as objective device-based measures and biological measures (e.g., hair antiretroviral concentration and viral load) to examine the validity of self-reported measures in HIV research and clinic care. Fifth, data were not available in the current study on some important factors (e.g., substance use) that might influence both self-reported measures and hair antiretroviral concentration [50,51].…”

Research in the Time of Coronavirus: Continuing Ongoing Studies in the Midst of the COVID-19 Pandemic

“…For example medication adherence can be evaluated by drug hair concentrations using mail-in hair samples [23][24][25] and text messaged photographs of pill counts or refill dates [23][24][25]. Adherence has been monitored using medication event monitoring system (MEMS) caps, ingestion sensors, and "wise"-products [26][27][28][29][30].…”

Antibody-mediated immune exclusion of HIV

“…Topical administration of anti-HIV microbicides has been fraught with compliance issues and has not yielded reliable protection in clinical trials [41–42]. Undoubtedly, topical formulations of recombinant anti-HIV mAbs may encounter similar obstacles.…”