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

TitleEmtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing.
Publication TypePublication
Year of Publication2016
AuthorsCastillo-Mancilla J, Seifert S, Campbell K, Coleman S, McAllister K, Zheng J-H, Gardner EM, Liu A, Glidden DV, Grant R, Hosek S, Wilson CM, Bushman LR, MaWhinney S, Anderson PL
JournalAntimicrob Agents Chemother
Volume60
Issue11
Pagination6692-6697
Date Published2016 11
ISSN1098-6596
KeywordsAdolescent, Adult, Aged, Anti-HIV Agents, Case-Control Studies, Dried Blood Spot Testing, Drug Administration Schedule, Emtricitabine, Female, Half-Life, HIV, HIV Infections, Humans, Male, Medication Adherence, Middle Aged, Prospective Studies, Tenofovir
Abstract

<p>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.).</p>

DOI10.1128/AAC.01017-16
Alternate JournalAntimicrob. Agents Chemother.
PubMed ID27572401
PubMed Central IDPMC5075074
Grant ListU01 HD040533 / HD / NICHD NIH HHS / United States
T32 AI007447 / AI / NIAID NIH HHS / United States
U01 AI084735 / AI / NIAID NIH HHS / United States
R01 AI118575 / AI / NIAID NIH HHS / United States
K23 AI104315 / AI / NIAID NIH HHS / United States
U01 AI106499 / AI / NIAID NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States