Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing

Antimicrob Agents Chemother. 2016 Oct 21;60(11):6692-6697. doi: 10.1128/AAC.01017-16. Print 2016 Nov.


New objective measures of antiretroviral adherence are needed. We determined if emtricitabine triphosphate (FTC-TP) in dried blood spots (DBS) can be used as a marker of recent dosing with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC). The half-life of FTC-TP was estimated in DBS samples obtained from an intensive pharmacokinetic (PK) study of coformulated TDF-FTC in HIV-negative and HIV-infected participants. The concordance of quantifiable FTC-TP in DBS with tenofovir (TFV)/FTC in plasma was evaluated by utilizing paired plasma-DBS samples from participants enrolled in 2 large preexposure prophylaxis (PrEP) open-label trials. The time to FTC-TP nondetectability after TDF-FTC dosing was evaluated utilizing DBS from HIV-negative participants enrolled in a directly observed therapy study of variable adherence to TDF-FTC. The mean (95% confidence interval [CI]) terminal half-life of FTC-TP in the PK study was 35 (23 to 47) h. A total of 143/163 (88%) samples obtained 0 to 48 h post-TDF-FTC dose had quantifiable FTC-TP in DBS, compared with 2/93 (2%) and 0/87 (0%) obtained >48 and >96 h postdose. In 746 paired plasma-DBS samples from 445 participants enrolled in PrEP trials, when both TFV/FTC in plasma were below the limit of quantification, FTC-TP was as well in 98.9% of the samples, and when either TFV or FTC in plasma was quantifiable, FTC-TP was as well in 90.5% of the samples. The half-life of FTC-TP in DBS is short relative to that of TFV-diphosphate (TFV-DP), making it a surrogate for TFV-FTC detection in plasma. FTC-TP can be quantified in DBS simultaneously with TFV-DP, which quantifies cumulative adherence to TDF-FTC. (The clinical trials discussed in this article have been registered at ClinicalTrials.gov under identifiers NCT01040091, NCT02022657, NCT00458393, NCT01772823, and NCT02012621.).

Publication types

  • Observational Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / blood*
  • Anti-HIV Agents / pharmacokinetics
  • Case-Control Studies
  • Dried Blood Spot Testing / methods*
  • Drug Administration Schedule
  • Emtricitabine / blood*
  • Emtricitabine / pharmacokinetics
  • Female
  • HIV / drug effects
  • HIV / growth & development
  • HIV Infections / blood*
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • Half-Life
  • Humans
  • Male
  • Medication Adherence / statistics & numerical data*
  • Middle Aged
  • Prospective Studies
  • Tenofovir / blood*
  • Tenofovir / pharmacokinetics


  • Anti-HIV Agents
  • Tenofovir
  • Emtricitabine

Associated data

  • ClinicalTrials.gov/NCT00458393
  • ClinicalTrials.gov/NCT01772823
  • ClinicalTrials.gov/NCT02012621
  • ClinicalTrials.gov/NCT01040091
  • ClinicalTrials.gov/NCT02022657