Oral Fluid Drug Monitoring: Lessons from a PrEP Adherence Trial

In short: Measuring a drug directly in oral fluid is less invasive than a blood draw. A 2026 randomized trial in Thailand found that emtricitabine (FTC), one of the two drugs in daily oral PrEP, could be detected in oral fluid and flagged recent missed doses with high sensitivity, though with modest specificity. The other drug, tenofovir, was rarely detectable. Here is what the study did, what it found, and what it means for anyone designing an oral fluid drug-monitoring study.

This article describes published research. Oasis Diagnostics devices are for research use. Nothing here is medical advice.

Key takeaways

• In the TARGET trial, 22 adults provided 241 oral fluid samples, collected with the Accu•SAL device, alongside blood plasma samples.
• Among 165 oral fluids collected within 48 hours of the last dose, emtricitabine was detectable in 53.3% and tenofovir in only 9.0%.
• An emtricitabine level below 7.5 ng/mL identified recent non-adherence with 90% sensitivity and 65% specificity.
• Oral fluid emtricitabine tracked plasma emtricitabine (correlation 0.66); oral fluid tenofovir did not track plasma tenofovir.
• The authors say a follow-up test would be needed to confirm adherence, because 65% specificity means some adherent people would be flagged.

Why look at drugs in oral fluid?

Daily oral PrEP (emtricitabine/tenofovir disoproxil fumarate) is a first-line option recommended by the World Health Organization, but how well it works depends heavily on taking it consistently. The study’s authors note that self-report, pill counts and pharmacy refills are the traditional ways to monitor adherence, and that measuring drug directly in a biological sample gives a more accurate picture of real-time drug levels and is less affected by recall or social desirability bias.

Blood and urine can be measured, but the authors point out that oral fluid is less invasive, easier to collect and needs minimal privacy. That matters in settings where oral fluid is already used, such as rapid HIV self-tests.

What the TARGET trial did

The open-label randomized pharmacokinetic trial recruited healthy adults aged 18–49 in Thailand. Participants were randomized 1:1:1 to take 2, 4 or 7 doses a week of tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg for six weeks, with directly observed dosing and the time of every dose recorded. That design gave the researchers exact knowledge of when each person last took a dose.

Oral fluid (1 mL) and a matched blood sample were collected before the next scheduled dose during the dosing phase, with extra collections during a washout week. In total the team collected 241 oral fluid samples from 22 HIV-negative adults. Oral fluid was collected with Accu•SAL devices, stored at −70 °C, and drug levels were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS), with a limit of detection of 5 ng/mL in oral fluid.

What they found

The authors conclude emtricitabine in oral fluid may be a promising pharmacologic marker for identifying recent PrEP non-adherence, even one missed dose. They state that tenofovir had lower concentrations in oral fluid and is not suitable for adherence monitoring.

Limits to keep in mind

• Small, controlled study. 22 healthy adults under directly observed therapy is not the same as real-world use.
• Modest specificity. At 65%, a low result does not prove someone skipped a dose. The authors suggest a follow-up test with high specificity to confirm adherence status, and say the primary goal of a monitoring test should be to find non-adherent users early.
• Time-dependent. Detectability fell between 24 and 48 hours after a dose. The authors assumed samples more than 48 hours after a dose had undetectable emtricitabine, based on earlier research and their pilot, and note that 26% of samples taken exactly 48 hours after a dose were still detectable.

What this means for oral fluid study design

1. Know when the last dose was. In this trial the dosing time was recorded and observed. Without it, an oral fluid drug level is hard to interpret.
2. Choose the right analyte. Different drug molecules behave differently in oral fluid. Here emtricitabine worked and tenofovir did not.
3. Collect a consistent volume. The trial collected 1 mL of oral fluid per sample. Devices with a volume check make that easier.
4. Plan storage and assay sensitivity together. Samples were frozen at −70 °C and measured by LC-MS/MS with a 5 ng/mL detection limit in oral fluid.

The collection device

Accu•SAL is an oral fluid collection system for standardized collection of whole saliva from the side of the tongue, designed for drug and drug metabolite testing. A sample volume adequacy indicator is built into the device handle. If a sample is short, the user can calculate the absolute quantity of saliva collected, and from that a dilution factor for the downstream immunoassay.

• Accu•SAL oral fluid collection system
• Research that used Oasis devices

Sources

1. Niu X, et al. Oral fluid concentrations of tenofovir and emtricitabine for monitoring HIV antiretroviral adherence: findings from a randomized trial with directly observed therapy (TARGET study). Open Forum Infect Dis. 2026. https://doi.org/10.1093/ofid/ofaf766