Evidence map›Paper›PMID 31335938›Full record

ArticleThe Journal of antimicrobial chemotherapy2019

Assessing the lymphoid tissue bioavailability of antiretrovirals in human primary lymphoid endothelial cells and in mice.

Shetty Ravi Dyavar, Nagsen Gautam, Anthony T Podany, Lee C Winchester, Jonathan A Weinhold, Timothy M Mykris, Kayla M Campbell, Yazen Alnouti, Courtney V Fletcher

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

22 citing papers in PubMed, 29 citations in OpenAlex.

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  14. The Contributions of Clinical Pharmacology to HIV Cure Research.Clinical pharmacology and therapeutics · 2021
    Review
  15. Pharmacology of HIV Cure: Site of Action.Clinical pharmacology and therapeutics · 2021
    Review
  16. Review
  17. Article
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  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

9 authors at 1 institution in 1 country.

Shetty Ravi DyavarAntiviral Pharmacology Laboratory, University of Nebraska Medical Center (UNMC) Center for Drug Discovery, UNMC, Omaha, NE, USA.
Nagsen GautamDepartment of Pharmaceutical Sciences, College of Pharmacy, UNMC, Omaha, NE, USA.
Anthony T PodanyAntiviral Pharmacology Laboratory, University of Nebraska Medical Center (UNMC) Center for Drug Discovery, UNMC, Omaha, NE, USA.
Lee C WinchesterAntiviral Pharmacology Laboratory, University of Nebraska Medical Center (UNMC) Center for Drug Discovery, UNMC, Omaha, NE, USA.
Jonathan A WeinholdAntiviral Pharmacology Laboratory, University of Nebraska Medical Center (UNMC) Center for Drug Discovery, UNMC, Omaha, NE, USA.
Timothy M MykrisAntiviral Pharmacology Laboratory, University of Nebraska Medical Center (UNMC) Center for Drug Discovery, UNMC, Omaha, NE, USA.
Kayla M CampbellAntiviral Pharmacology Laboratory, University of Nebraska Medical Center (UNMC) Center for Drug Discovery, UNMC, Omaha, NE, USA.
Yazen AlnoutiDepartment of Pharmaceutical Sciences, College of Pharmacy, UNMC, Omaha, NE, USA.
Courtney V FletcherAntiviral Pharmacology Laboratory, University of Nebraska Medical Center (UNMC) Center for Drug Discovery, UNMC, Omaha, NE, USA.
University of Nebraska Medical Center · US

Funding

The Lymphoid Tissue Pharmacology of Antiretroviral DrugsR01AI124965 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI FLETCHER, COURTNEY V · 2016 to 2020
$3.7M
NIAID NIH HHS R01 AI124965
6 · The paper itself

Abstract

backgroundThe secondary lymphoid tissues (LTs), lymph nodes (LNs) and gut-associated lymphoid tissue (GALT) are considered reservoirs for HIV. Antiretrovirals (ARVs) have lower penetration into LT. In vitro models predictive of ARV LT penetration have not been established.

objectivesTo develop an in vitro model of LT bioavailability using human lymphoid endothelial cells (HLECs) and investigate its predictability with in vivo pharmacokinetic (PK) studies in mice.

methodsARV bioavailability in HLECs was evaluated at the maximum plasma concentration (Cmax) observed in HIV-infected patients. ARVs were: abacavir, atazanavir, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, maraviroc, raltegravir, rilpivirine, ritonavir, tenofovir disoproxil fumarate and the PK booster cobicistat. The LT PK of representative drugs showing high (efavirenz), intermediate (dolutegravir) and low (emtricitabine) HLEC bioavailability was investigated in BALB/c mice given 50/10/30 mg/kg efavirenz/dolutegravir/emtricitabine orally, daily for 3 days. The concordance of in vitro and in vivo ARV bioavailability was examined.

resultsARVs showed high (>67th percentile; rilpivirine, efavirenz, elvitegravir and cobicistat), intermediate (67th-33rd percentile; ritonavir, tenofovir disoproxil fumarate, dolutegravir and maraviroc) and low (<33rd percentile; atazanavir, darunavir, raltegravir, emtricitabine and abacavir) HLEC bioavailability. The hierarchy of efavirenz, dolutegravir and emtricitabine bioavailability in LN, gut and brain tissues of mice was: efavirenz>dolutegravir>emtricitabine.

conclusionsARVs displayed distinct HLEC penetration patterns. PK studies of representative ARVs in LT of mice were concordant with HLEC bioavailability. These findings support further development of this approach and its translational predictability in humans.

Indexed as

AnimalsAnti-Retroviral AgentsBiological AvailabilityCells, CulturedEndothelial CellsHIV-1HIV InfectionsHumansLymphoid TissueMaleMiceMice, Inbred BALB CAnti-Retroviral Agents

Identifiers

PMID31335938
PMCPMC6753470
OpenAlexW2963347187

What OpenQuestion holds

Textmetadata
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.