Evidence map›Paper›PMID 36684094›Full record

ArticleBioengineering & translational medicine2023

REverSe TRanscrIptase chain termination (RESTRICT) for selective measurement of nucleotide analogs used in HIV care and prevention.

Ayokunle O Olanrewaju, Benjamin P Sullivan, Alicia H Gim, Cosette A Craig, Derin Sevenler, Andrew T Bender, Paul K Drain, Jonathan D Posner

Open access · goldAbstract read
In one paragraph

Article in Bioengineering & translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Ayokunle O OlanrewajuDepartment of Mechanical Engineering University of Washington Seattle Washington USA.ORCID https://orcid.org/0000-0003-4776-1774
Benjamin P SullivanDepartment of Mechanical Engineering University of Washington Seattle Washington USA.ORCID https://orcid.org/0000-0002-3520-1684
Alicia H GimDepartment of Chemical Engineering University of Washington Seattle Washington USA.
Cosette A CraigDepartment of Mechanical Engineering University of Washington Seattle Washington USA.ORCID https://orcid.org/0000-0001-5917-3561
Derin SevenlerCenter for Engineering in Medicine and Surgery Massachusetts General Hospital Boston Massachusetts USA.ORCID https://orcid.org/0000-0002-0327-5638
Andrew T BenderDepartment of Mechanical Engineering University of Washington Seattle Washington USA.ORCID https://orcid.org/0000-0003-4349-4488
Paul K DrainDepartment of Epidemiology University of Washington Seattle Washington USA.ORCID https://orcid.org/0000-0002-9569-4097
Jonathan D PosnerDepartment of Mechanical Engineering University of Washington Seattle Washington USA.ORCID https://orcid.org/0000-0001-8860-050X
University of Washington · USMassachusetts General Hospital · US

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
Technology Training and Dissemination CoreU54EB027690 · NIBIB · EMORY UNIVERSITY · PI Wilbur A Lam · 2018 to 2026
$96.1M
A novel REverSe Transcriptase Chain Termination (RESTRICT) assay for near-patient, objective monitoring of long-term PrEP adherenceR01AI157756 · NIAID · UNIVERSITY OF WASHINGTON · PI DRAIN, PAUL K, POSNER, JONATHAN D · 2021 to 2025
$3.8M
A Rapid Point-of-Care Test to Improve ART and PrEP AdherenceR01AI136648 · NIAID · UNIVERSITY OF WASHINGTON · PI DRAIN, PAUL K · 2018 to 2020
$2.3M
A Point-of-Care Assay to Measure Tenofovir for Monitoring PrEP and ART AdherenceR21AI127200 · NIAID · UNIVERSITY OF WASHINGTON · PI DRAIN, PAUL K · 2016 to 2017
$396k
Intracellular delivery of DNA-editing proteins by viscoelastic cell stretchingK99AI167063 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SEVENLER, DERIN · 2022 to 2023
$273k
NIAID NIH HHS K99 AI167063NIAID NIH HHS P30 AI027757NIAID NIH HHS R01 AI136648NIAID NIH HHS R01 AI157756NIAID NIH HHS R21 AI127200NIBIB NIH HHS U54 EB027690
6 · The paper itself

Abstract

Sufficient drug concentrations are required for efficacy of antiretroviral drugs used in HIV care and prevention. Measurement of nucleotide analogs, included in most HIV medication regimens, enables monitoring of short- and long-term adherence and the risk of treatment failure. The REverSe TRanscrIptase Chain Termination (RESTRICT) assay rapidly infers the concentration of intracellular nucleotide analogs based on the inhibition of DNA synthesis by HIV reverse transcriptase enzyme. Here, we introduce a probabilistic model for RESTRICT and demonstrate selective measurement of multiple nucleotide analogs using DNA templates designed according to the chemical structure of each drug. We measure clinically relevant concentrations of tenofovir diphosphate, emtricitabine triphosphate, lamivudine triphosphate, and azidothymidine triphosphate with agreement between experiment and theory. RESTRICT represents a new class of activity-based assays for therapeutic drug monitoring in HIV care and could be extended to other diseases treated with nucleotide analogs.

Indexed as

adherence monitoringenzymatic assaynucleotide analognucleotide reverse transcriptase inhibitorreverse transcriptase inhibitortenofovir diphosphatetherapeutic drug monitoring

Identifiers

PMID36684094
PMCPMC9842053
OpenAlexW4285387973

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.