Evidence map›Paper›PMID 26771889›Full record

ArticleVirology2016

Mucosal tissue pharmacokinetics of the integrase inhibitor raltegravir in a humanized mouse model: Implications for HIV pre-exposure prophylaxis.

Milena Veselinovic, Kuo-Hsiung Yang, Craig Sykes, Leila Remling-Mulder, Angela D M Kashuba, Ramesh Akkina

Abstract read
In one paragraph

Article in Virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

8 citing papers in PubMed, 9 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

6 authors at 2 institutions in 1 country.

Milena VeselinovicDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Kuo-Hsiung YangEshelman School of Pharmacy, NC, USA.
Craig SykesEshelman School of Pharmacy, NC, USA.
Leila Remling-MulderDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Angela D M KashubaEshelman School of Pharmacy, NC, USA; School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Ramesh AkkinaDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA. Electronic address: akkina@colostate.edu.
Colorado State University · USUniversity of North Carolina at Chapel Hill · US

Funding

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Modeling Next Generation HIV PrEP in Humanized MiceR01AI100845 · NIAID · COLORADO STATE UNIVERSITY · PI AKKINA, RAMESH · 2012 to 2014
$2.0M
Efficacy Testing of HIV-Specific Microbicides in Humanized MiceR56AI095101 · NIAID · COLORADO STATE UNIVERSITY · PI AKKINA, RAMESH · 2012 to 2012
$445k
NIAID NIH HHS P30 AI050410NIAID NIH HHS P30AI50410NIAID NIH HHS R01 AI100845NIAID NIH HHS R01AI100845NIAID NIH HHS R56 AI095101NIAID NIH HHS R56AI095101
6 · The paper itself

Abstract

Orally administered anti-retroviral drugs show considerable promise for HIV/AIDS pre-exposure prophylaxis (PrEP). For the success of these strategies, pharmacokinetic (PK) data defining the optimal concentration of the drug needed for protection in relevant mucosal exposure sites is essential. Here we employed a humanized mouse model to derive comprehensive PK data on the HIV integrase inhibitor raltegravir (RAL), a leading PrEP drug candidate. Under steady state conditions following oral dosing, plasma and multiple mucosal tissues were sampled simultaneously. RAL exhibited higher drug exposure in mucosal tissues relative to that in plasma with one log higher exposure in vaginal and rectal tissue and two logs higher exposure in intestinal mucosa reflecting the trends seen in the human studies. These data demonstrate the suitability of RAL for HIV PrEP and validate the utility of humanized mouse models for deriving important preclinical PK-PD data.

Indexed as

AnimalsDisease Models, AnimalFemaleHIV-1HIV InfectionsHIV Integrase InhibitorsHumansMiceMice, Inbred BALB CMucous MembranePre-Exposure ProphylaxisRaltegravir PotassiumHIV Integrase InhibitorsRaltegravir PotassiumMucosal tissue PK of raltegravirPharmacokinetics of raltegravir in hu-micePK–PD studies on raltegravirPre-Exposure Prophylaxis for HIV/AIDSRaltegravir for HIV prevention

Identifiers

PMID26771889
PMCPMC5906038
OpenAlexW2222649585

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.