Evidence map›Paper›PMID 30121315›Full record

ArticleJournal of pharmaceutical sciences2018

Three HIV Drugs, Atazanavir, Ritonavir, and Tenofovir, Coformulated in Drug-Combination Nanoparticles Exhibit Long-Acting and Lymphocyte-Targeting Properties in Nonhuman Primates.

Simone Perazzolo, Laura M Shireman, Josefin Koehn, Lisa A McConnachie, John C Kraft, Danny D Shen, Rodney J Y Ho

Open access · greenAbstract read
In one paragraph

Article in Journal of pharmaceutical sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

31 citing papers in PubMed, 44 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

7 authors at 1 institution in 1 country.

Simone PerazzoloDepartment of Pharmaceutics, University of Washington, Seattle, Washington 98195.
Laura M ShiremanDepartment of Pharmaceutics, University of Washington, Seattle, Washington 98195.
Josefin KoehnDepartment of Pharmaceutics, University of Washington, Seattle, Washington 98195.
Lisa A McConnachieDepartment of Pharmaceutics, University of Washington, Seattle, Washington 98195.
John C KraftDepartment of Pharmaceutics, University of Washington, Seattle, Washington 98195.
Danny D ShenDepartment of Pharmaceutics, University of Washington, Seattle, Washington 98195.
Rodney J Y HoDepartment of Pharmaceutics, University of Washington, Seattle, Washington 98195; Department of Bioengineering, University of Washington, Seattle, Washington 98195. Electronic address: rodneyho@uw.edu.
University of Washington · US

Funding

Washington National Primate Research CenterP51OD010425 · OD · UNIVERSITY OF WASHINGTON · PI Mari Ostendorf · 2012 to 2026
$201.8M
Targeted Long-acting Combination Antiretroviral Therapy (TLC-ART)UM1AI120176 · NIAID · UNIVERSITY OF WASHINGTON · PI COLLIER, ANN CORNWALL, HO, RODNEY J.Y. · 2015 to 2019
$15.0M
Pharmacological Sciences SupplementT32GM007750 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 1985 to 2023
$12.6M
pH Responsive anti-HIV NanoparticlesR01AI077390 · NIAID · UNIVERSITY OF WASHINGTON · PI HO, RODNEY J.Y. · 2009 to 2013
$3.9M
NIAID NIH HHS R01 AI077390NIAID NIH HHS UM1 AI120176NIGMS NIH HHS T32 GM007750NIH HHS P51 OD010425
6 · The paper itself

Abstract

Drug-combination nanoparticles (DcNPs) administered subcutaneously represent a potential long-acting lymphatic-targeting treatment for HIV infection. The DcNP containing lopinavir (LPV)-ritonavir (RTV)-tenofovir (TFV), Targeted-Long-Acting-Antiretroviral-Therapy product candidate 101 (TLC-ART 101), has shown to provide long-acting lymphocyte-targeting performance in nonhuman primates. To extend the TLC-ART platform, we replaced TLC-ART 101 LPV with second-generation protease inhibitor, atazanavir (ATV). Pharmacokinetics of the ATV-RTV-TFV DcNP was assessed in macaques, in comparison to the equivalent free drug formulation and to the TLC-ART 101. After single subcutaneous administration of the DcNP formulation, ATV, RTV, and TFV concentrations were sustained in plasma for up to 14 days, and in peripheral blood mononuclear cells for 8 to 14 days, compared with 1 to 2 days in those macaques treated with free drug combination. By 1 week, lymph node mononuclear cells showed significant levels for all 3 drugs from DcNPs, whereas the free controls were undetectable. Compared with TLC-ART 101, the ATV-RTV-TFV DcNP exhibited similar lymphocyte-targeted long-acting features for all 3 drugs and similar pharmacokinetics for RTV and TFV, whereas some pharmacokinetic differences were observed for ATV versus LPV. The present study demonstrated the flexibility of the TLC-ART's DcNP platform to include different antiretroviral combinations that produce targeted long-acting effects on both plasma and cells.

Indexed as

Drug Delivery SystemsAnimalsAnti-HIV AgentsAtazanavir SulfateCells, CulturedDelayed-Action PreparationsDrug CombinationsHIV InfectionsHumansLeukocytes, MononuclearLipidsLymphocytesMacaca nemestrinaMaleNanoparticlesRitonavirAnti-HIV AgentsAtazanavir SulfateDelayed-Action PreparationsDrug CombinationsLipidsRitonavirTenofovirAIDSdrug-combinationHIVlipid nanoparticle(s) (LNP)long-actingpreclinical pharmacokineticstargeted drug deliverytargeted therapy

Identifiers

PMID30121315
PMCPMC6553477
OpenAlexW2886420031

What OpenQuestion holds

Textmetadata
LicenceTDM
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.