Background
Adherence monitoring using drug concentrations for oral Pre-exposure Prophylaxis (PrEP) can identify people who need additional adherence support interventions or a transition to long-acting injectable regimens. Oral fluids are widely accepted as a convenient and confidential specimen type for HIV self-testing. This study evaluated the feasibility of detecting emtricitabine (FTC) and tenofovir (TFV) in oral fluids to monitor daily oral PrEP adherence.
Methods
We collected oral fluids from HIV-negative adults randomized to 2 or 4 or 7 doses/week with FTC/Tenofovir Disoproxil Fumarate for directly observed oral PrEP. Drug concentrations were measured using liquid chromatography tandem mass spectrometry. Drug levels below the limit of detection (LOD: 5 ng/mL) were considered as undetectable (0 ng/mL). Readouts below the limit of quantification (LOQ: 10 ng/mL) but above the LOD were imputed as half of the LOQ. Generalized Estimating Equations were used to examine associations between FTC/TFV detectability and the three dimensions of PrEP adherence: dosing recency (hours since last dose taken), cumulative dosing time (weeks since first dose), and dosing frequency (number of doses per week). We also assessed the diagnostic accuracy of FTC levels in oral fluids for predicting daily oral PrEP non-adherence(defined as having a time since last dose >24 hours).
Results
241 oral fluid specimens from 22 participants (41% female) were included. Among 165 oral fluid specimens with a time since last dose within 48 hours, 15 (9.0%) had detectable TFV, and 88 (53.3%) had detectable FTC. Median (interquartile range) FTC concentrations were 15 (0-141) ng/mL for 115 oral fluid specimens with time since the last dose ≤24 hours, and 0 (0-11) ng/mL for 50 oral fluid specimens with time since the last dose between 24 and 48 hours. Oral specimens collected between 24 and 48 hours since the last oral PrEP dose had significantly lower odds of having detectable FTC (odds ratio: 0.21, 95% CI: 0.11-0.38), as compared to specimens collected within 24 hours since the last oral PrEP dose. An FTC threshold of <7.5 ng/mL achieved a sensitivity of 90% (95% CI: 84%-94%) and a specificity of 65% (95% CI: 57%-74%) to identify recent PrEP non-adherence with one daily dose missed.
Conclusions
FTC can be detected in oral fluids and its absence may provide a reliable pharmacologic marker identifying non-adherence to daily PrEP dosing. TFV concentrations in oral fluids were low making it unsuitable for PrEP adherence monitoring.