3 years ago

Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots following Directly Observed Therapy: the DOT-DBS Study.

Edward M Gardner, Samantha MaWhinney, Kayla Campbell, Jennifer J Kiser, Jose R Castillo-Mancilla, Albert Y Liu, Cricket McHugh, Sharon M Seifert, Theresa Wagner, Lane R Bushman, Peter L Anderson, Mary Morrow, Mustafa Ibrahim, Susan Buchbinder
Studies of daily emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for HIV pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) modeled intracellular tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) to assess adherence and corresponding PrEP outcomes. We conducted a prospective, randomized, cross-over pharmacokinetic study of TFV-DP in DBS during 33%, 67% or 100% of daily dosing, under directly observed therapy (DOT). Participants were assigned to two 12-week dosing regimens, separated by a 12-week washout. Forty-eight adults (24 women) from Denver and San Francisco were included. TFV-DP exhibited a median half-life of 17 days, reaching steady-state in 8 weeks. TFV-DP was dose-proportional with mean (SD) steady-state concentrations of 530 (159), 997 (267), and 1542 (405) fmol/punch for the 33%, 67% and 100% arms, respectively. Prior work in MSM demonstrated clinically meaningful TFV-DP thresholds of 350, 700, and 1250 fmol/punch, which were estimated 25(th) percentiles for 2, 4, and 7 doses/wk. In the present study, corresponding TFV-DP was within 3% of the prior estimates and subgroups by site, race, and sex, were within 14% of prior estimates, although males had 17.6% (95%CI 6.5, 27.4%) lower TFV-DP compared with females. The thresholds of 350, 700, and 1250 fmol/punch were achieved by 75% of men taking ≥1.2, 3.1, and 6 doses/wk, and 75% of women taking ≥0.6, 2.1, and 5.3 doses/wk, indicating that lower dosing reached these thresholds for both sexes. In conclusion, TFV-DP arising from DOT was similar to previous estimates, and is useful for interpreting PrEP adherence and study outcomes.

Publisher URL: http://doi.org/10.1128/AAC.01710-17

DOI: 10.1128/AAC.01710-17

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.