Evidence map›Paper›PMID 28099191›Full record

ArticleAIDS (London, England)2017

Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma.

John C Kraft, Lisa A McConnachie, Josefin Koehn, Loren Kinman, Carol Collins, Danny D Shen, Ann C Collier, Rodney J Y Ho

2 registry-linked trialsOpen access · greenAbstract read
In one paragraph

Article in AIDS (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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.

NCT04530630 phase4completednot on this mapstarted 2020, after this paper: background citation

The Efficacy, Safety, and Tolerability of Switching to a Bictegravir (BIC)/Emtricitabine(FTC)/Tenofovir Alafenamide (TAF) Regimen in Virally Suppressed Human Immunodeficiency Viruses (HIV)-Positive Patients Post-Renal Transplant

TypeinterventionalSponsorWeill Medical College of Cornell UniversityRan2020 to 2024Enrolled20ConditionsHIV Infections, Renal Transplant RejectionArmsBIC/F/TAF 50Mg-200Mg-25Mg Tablet
NCT05850728 phase1completednot on this mapstarted 2023, after this paper: background citation

First in Human Clinical Trial of a Next Generation, Long-acting Injectable, Combination Antiretroviral Therapy Platform

TypeinterventionalSponsorUniversity of WashingtonRan2023 to 2024Enrolled12ConditionsHuman Immunodeficiency Virus, Treatment, Antiretroviral TherapyArmsTLC-ART
3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Delivering CRISPR to the HIV-1 reservoirs.Frontiers in microbiology · 2024
    Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Long-Acting Treatments for Hepatitis B.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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 1 institution in 1 country.

John C KraftaDepartment of Pharmaceutics bDepartment of Medicine cCenter for AIDS Research dDepartment of Bioengineering, University of Washington, Seattle, Washington, USA.
Lisa A McConnachie
Josefin Koehn
Loren Kinman
Carol Collins
Danny D Shen
Ann C Collier
Rodney J Y Ho
Johns Hopkins University Center for AIDS Research

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
NIAID NIH HHS UM1 AI120176NIH HHS P51 OD010425
6 · The paper itself

Abstract

objectiveThe aim of the present study was to determine whether a combination of anti-HIV drugs - tenofovir (TFV), lopinavir (LPV) and ritonavir (RTV) - in a lipid-stabilized nanosuspension (called TLC-ART101) could enhance and sustain intracellular drug levels and exposures in lymph node and blood cells above those in plasma.

designFour macaques were given a single dose of TLC-ART101 subcutaneously. Drug concentrations in plasma and mononuclear cells of the blood (PBMCs) and lymph nodes (LNMCs) were analysed using a validated combination LC-MS/MS assay.

resultsFor the two active drugs (TFV, LPV), plasma and PBMC intracellular drug levels persisted for over 2 weeks; PBMC drug exposures were three- to four-fold higher than those in plasma. Apparent terminal half-lives (t1/2) of TFV and LPV were 65.3 and 476.9 h in plasma, and 169.1 and 151.2 h in PBMCs. At 24 and 192 h, TFV and LPV drug levels in LNMCs were up to 79-fold higher than those in PBMCs. Analysis of PBMC intracellular TFV and its active metabolite TFV-diphosphate (TFV-DP) indicated that intracellular exposures of total TFV and TFV-DP were markedly higher and persisted longer than in humans and macaques dosed with oral TFV prodrugs, tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF).

conclusionsA simple, scalable three-drug combination, lipid-stabilized nanosuspension exhibited persistent drug levels in cells of lymph nodes and the blood (HIV host cells) and in plasma. With appropriate dose adjustment, TLC-ART101 may be a useful HIV treatment with a potential to impact residual virus in lymph nodes.

Indexed as

AnimalsAnti-HIV AgentsAntiretroviral Therapy, Highly ActiveBlood CellsChromatography, LiquidDelayed-Action PreparationsLymph NodesMacacaPlasmaSuspensionsTandem Mass SpectrometryAnti-HIV AgentsDelayed-Action PreparationsSuspensions

Identifiers

PMID28099191
PMCPMC5345888
OpenAlexW2577155621

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.