Oral Fluid Concentrations of Tenofovir and Emtricitabine for Monitoring HIV Antiretroviral Adherence: Findings From a Randomized Trial with Directly Observed Therapy (TARGET Study).

Background: Early identification of non-adherence to daily antiretroviral therapies may facilitate targeted transition to long-acting HIV regimens for individuals most likely to benefit. This study evaluated the feasibility of detecting emtricitabine (FTC) and tenofovir (TFV) in oral fluids to monitor daily oral pre-exposure prophylaxis (PrEP) adherence. Methods: We collected 241 oral fluids from 22 HIV-negative adults randomized to 2, 4, or 7 doses/week of oral PrEP with FTC/TDF for directly observed therapy. Generalized Estimating Equations were used to examine the associations between FTC/TFV detectability and three dimensions of PrEP adherence: dosing recency, cumulative dosing time, and dosing frequency. We also assessed the diagnostic accuracy of FTC levels in oral fluids for predicting daily oral PrEP non-adherence (time since the last dose >24 hours). Results: Among 165 oral fluids with a time since the last dose within 48 hours, 9.0% had detectable TFV, and 53.3% had detectable FTC. Compared with oral fluids collected within 24 hours since the last dose, those collected between 24 and 48 hours since the last dose had significantly lower odds of having detectable FTC (odds ratio: 0.21, 95% confidence interval [CI]: 0.11-0.38). 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%) for identifying recent PrEP non-adherence. Conclusions: FTC can be detected in oral fluids and may be a promising pharmacologic marker for identifying recent PrEP non-adherence as early as one dose missed. TFV had lower concentrations in oral fluids, and is not suitable for adherence monitoring.