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

• Published in: Antimicrobial agents and chemotherapy 2016-11, Vol.60 (11), p.6692-6697
• Main Authors: Castillo-Mancilla, Jose, Seifert, Sharon, Campbell, Kayla, Coleman, Stacey, McAllister, Kevin, Zheng, Jia-Hua, Gardner, Edward M, Liu, Albert, Glidden, David V, Grant, Robert, Hosek, Sybil, Wilson, Craig M, Bushman, Lane R, MaWhinney, Samantha, Anderson, Peter L
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anti-HIV Agents; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacokinetics; Case-Control Studies; Dried Blood Spot Testing; Dried Blood Spot Testing - methods; Drug Administration Schedule; Emtricitabine; Emtricitabine - blood; Emtricitabine - pharmacokinetics; Female; Half-Life; HIV - drug effects; HIV - growth & development; HIV Infections; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - virology; Humans; Lentivirus; Male; Medication Adherence; Medication Adherence - statistics & numerical data; Middle Aged; Pharmacology; Prospective Studies; Retroviridae; Tenofovir; Tenofovir - blood; Tenofovir - pharmacokinetics
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01017-16

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.).