title: Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing.
abstract: 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.).
authors: Division of Infectious Diseases, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Jose
authors: J
authors: Castillo-Mancilla
authors: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Sharon
authors: S
authors: Seifert
authors: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Kayla
authors: K
authors: Campbell
authors: Division of Infectious Diseases, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Stacey
authors: S
authors: Coleman
authors: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Kevin
authors: K
authors: McAllister
authors: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Jia-Hua
authors: JH
authors: Zheng
authors: Division of Infectious Diseases, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Edward M
authors: EM
authors: Gardner
authors: Bridge HIV, San Francisco Department of Public Health, San Francisco, California, USA.
authors: Albert
authors: A
authors: Liu
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
authors: David V
authors: DV
authors: Glidden
authors: Gladstone Institute, University of California, San Francisco, California, USA.
authors: Robert
authors: R
authors: Grant
authors: Department of Psychiatry, John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois, USA.
authors: Sybil
authors: S
authors: Hosek
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Craig M
authors: CM
authors: Wilson
authors: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Lane R
authors: LR
authors: Bushman
authors: Department of Biostatistics and Bioinformatics, Colorado School of Public Health, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Samantha
authors: S
authors: MaWhinney
authors: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA peter.anderson@ucdenver.edu.
authors: Peter L
authors: PL
authors: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics; D016022:Case-Control Studies; D059788:Dried Blood Spot Testing / Q000379:methods; D004334:Drug Administration Schedule; D000068679:Emtricitabine / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D006678:HIV / Q000187:drug effects / Q000254:growth & development; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000821:virology; D011446:Prospective Studies; D000068698:Tenofovir / Q000097:blood / Q000493:pharmacokinetics; D000068456:Clinical Studies as Topic; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents; D000068679:Emtricitabine; D000068698:Tenofovir