Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar 1;98(3):291-299.
doi: 10.1097/QAI.0000000000003570.

A Cross-Biomeasure Study to Optimize Antiretroviral Adherence Estimation

Aaron S Devanathan  1 , Amanda J Poliseno  2 , Nicole R White  2 , Amanda P Schauer  2 , Craig Sykes  2 , Ann Marie K Weideman  3   4 , Kayla W Kilpatrick  5 , Michael G Hudgens  3   4 , Cynthia L Gay  5 , Elias P Rosen  2 , Julie B Dumond  2 , Angela D M Kashuba  2   5 , Mackenzie L Cottrell  2
Affiliations

A Cross-Biomeasure Study to Optimize Antiretroviral Adherence Estimation

Aaron S Devanathan et al. J Acquir Immune Defic Syndr. .

Abstract

Background: Incomplete adherence to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) reduces effectiveness. Adherence biomeasures (ie, drug concentrations in biological specimen) are more accurate than self-report. TDF/FTC's intracellular active metabolites (tenofovir-diphosphate; TFVdp and FTC-triphosphate; FTCtp) can be quantified in different types of blood samples to estimate adherence. To optimize adherence estimation, we investigated approaches to measure TFVdp and FTCtp in 4 blood matrices.

Methods: Twelve HIV-negative, healthy volunteers were enrolled in a single-center, open-label, 3-phase, directly observed therapy study. LC-MS/MS methods quantified TFVdp/FTCtp in dried blood spots, volumetrically accurate microsampling, upper layer packed cells, and peripheral blood mononuclear cells (PBMCs). Noncompartmental analysis estimated half-lives and accumulation ratios. Correlations characterized relationships between clinical variables and exposure. Regression models were fit to determine concentrations associated with <4 and ≥4 doses/week; correct classification percentages were determined.

Results: Terminal half-life estimates of 3-4 vs 15-22 days distinguished between moderate-term (FTCtp in all samples; TFVdp in PBMCs) versus long-term (TFVdp in red blood cell-containing matrices) measures. Model-derived thresholds accurately categorized <4 and ≥4 doses/week when including both metabolites for 14- and 28-day dosing periods (81%-91% and 82%-85%, respectively). Within each classification and regression trees analyses containing both moderate- and long-term measures, dried blood spots exhibited highest accuracy to predict stable (74%-94%) and changing (42%-47%) adherence patterns.

Conclusions: We demonstrate higher accuracy of moderate-term biomeasures to classify adherence over a 14-day period compared with long-term biomeasures to classify adherence over a 28-day period. Combined moderate- and long-term biomeasures predicted stable and changing adherence patterns, with dried blood spots exhibiting highest accuracy.

PubMed Disclaimer

Conflict of interest statement

The authors have no funding or conflicts of interest to disclose.

References

    1. Brault MA, Spiegelman D, Hargreaves J, Nash D, Vermund SH. Treatment as prevention: concepts and challenges for reducing HIV incidence. J Acquir Immune Defic Syndr. 2019;82 Suppl 2(2):S104–S112. doi: 10.1097/QAI.0000000000002168 - DOI - PMC - PubMed
    1. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587–2599. doi: 10.1056/NEJMoa1011205 - DOI - PMC - PubMed
    1. Molina J-M, Capitant C, Spire B, et al. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med. 2015;373(23):2237–2246. doi: 10.1056/NEJMoa1506273 - DOI - PubMed
    1. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367(5):411–422. doi: 10.1056/NEJMoa1202614 - DOI - PMC - PubMed
    1. Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372(6):509–518. doi: 10.1056/NEJMoa1402269 - DOI - PMC - PubMed

MeSH terms