Utility of Different Adherence Measures for PrEP: Patterns and Incremental Value

Abstract

Measuring PrEP adherence remains challenging. In 2009–2010, the International AIDS Vaccine Initiative randomized phase II trial participants to daily tenofovir disoproxil fumarate/emtricitabine or placebo in Uganda and Kenya. Adherence was measured by electronic monitoring (EM), self-report (SR), and drug concentrations in plasma and hair. Each adherence measure was categorised as low, moderate, or high and also considered continuously; the incremental value of combining measures was determined. Forty-five participants were followed over 4 months. Discrimination for EM adherence by area under receiver operating curves (AROC) was poor for SR (0.53) and best for hair (AROC 0.85). When combining hair with plasma or hair with self-report, discrimination was improved (AROC > 0.9). Self-reported adherence was of low utility by itself. Hair level was the single best PK measure to predict EM-assessed adherence; the other measurements had lower discrimination values. Combining short-term (plasma) and long-term (hair) metrics could be useful to assess patterns of drug-taking in the context of PrEP.

Adherence Measurements in HIV: New Advancements in Pharmacologic Methods and Real-Time Monitoring

“…While DBS concentrations could be used to estimate average dose intake over a preceding period of time (i.e., ~8 weeks), hair drug concentrations could be used to quantify longer drug exposure, including to non TFV/FTC-based regimens. In addition, measures of cumulative and short-term exposure (i.e., plasma drug levels), could also be combined to assess drug intake patterns in ART and PrEP[113]. Furthermore, coupling pharmacologic measures with RTAM is an attractive strategy that remains largely unknown (only available data are with DBS[60]), and should be a focus of future research in the field.…”

Smartphone-Based Contingency Management Intervention to Improve Pre-Exposure Prophylaxis Adherence: Pilot Trial (Preprint)

“…Also, no composite adherence scores worsened over the course of the study. Our use of biomarker as an adherence outcome is strength given that there is substantial within-subject variability in adherence based on the measurement method selected among individuals on PrEP [56]. Alternative methods, such as self-report [57] and electronic pill bottles [58] among young MSM have noted limitations.…”

An enzymatic assay to measure long-term adherence to pre-exposure prophylaxis and antiretroviral therapy

“…2 As access to ART and PrEP improves globally, adherence to medication is increasingly becoming a challenge in HIV treatment and prevention. [3][4][5] Poor adherence to ART among PLHIV leads to viral rebound, emergence of drug-resistant HIV, and treatment failure. 6 Poor adherence to PrEP reduces individual and community-level HIV prevention benefits.…”

“…3,12 There are several approaches for measuring ART and PrEP adherence. Subjective measures of adherence, such as self-reports and surveys, 3,13 pill counts and tracking of pharmacy refills, 3,4,14 and wireless pill containers, 15,16 do not provide proof of actual pill ingestion and have been shown to be inaccurate. 3 Digital pills with radio frequency transmitters embedded in gel caps provide proof of pill ingestion and information about short and long-term adherence patterns, 17 but require an individual to wear an RFID receiver that transmits the signal to a cloud-based server, and concerns around cost and privacy could limit acceptance by patients in global settings.…”

“…25 There is considerable interest in developing drug-level assays that can be implemented with minimal capital investment, equipment, and personnel, and that could readily available to physicians. 3,4 In this paper, we develop an enzymatic assay, termed REverse TranscrIptase Chain Termination (RESTRICT), for ART and PrEP adherence monitoring. The assay takes inspiration from the mechanism of action of TFV-DP on HIV RT and infers drug levels by measuring the length of cDNA generated by RT in the presence of DNA building blocks.…”