Evidence map›Paper›PMID 30333308›Full record

ArticleJCI insight2018

Determinants of the efficacy of HIV latency-reversing agents and implications for drug and treatment design.

Ruian Ke, Jessica M Conway, David M Margolis, Alan S Perelson

Abstract read
In one paragraph

Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Review
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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

4 authors.

Ruian KeDepartment of Mathematics, North Carolina State University, Raleigh, North Carolina, USA.
Jessica M ConwayDepartment of Mathematics and Center for Infectious Disease Dynamics, Pennsylvania State University, State College, Pennsylvania, USA.
David M MargolisUniversity of North Carolina (UNC) HIV Cure Center, UNC Institute of Global Health and Infectious Diseases.
Alan S PerelsonTheoretical Biology and Biophysics Group, MS-K710, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.

Funding

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Collaboratory of AIDS Researchers for Eradication (CARE)UM1AI126619 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARGOLIS, DAVID M. · 2016 to 2020
$23.2M
Viral dynamics of rebound and control following early treatment of HIV/SIVP01AI131365 · NIAID · BOSTON COLLEGE · PI WHITNEY, JAMES BURTON · 2017 to 2021
$7.5M
A Pilot Trial of the effect of Vorinostat and AGS-004 on Persistent HIV-1 InfectionU01AI117844 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARGOLIS, DAVID M. · 2015 to 2019
$6.8M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
Immune System Modeling/HIVR01AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1990 to 2021
$3.7M
NIAID NIH HHS P01 AI131365NIAID NIH HHS P30 AI050410NIAID NIH HHS R01 AI028433NIAID NIH HHS U01 AI117844NIAID NIH HHS UM1 AI126619NIH HHS R01 OD011095
6 · The paper itself

Abstract

HIV eradication studies have focused on developing latency-reversing agents (LRAs). However, it is not understood how the rate of latent reservoir reduction is affected by different steps in the process of latency reversal. Furthermore, as current LRAs are host-directed, LRA treatment is likely to be intermittent to avoid host toxicities. Few careful studies of the serial effects of pulsatile LRA treatment have yet been done. This lack of clarity makes it difficult to evaluate the efficacy of candidate LRAs or predict long-term treatment outcomes. We constructed a mathematical model that describes the dynamics of latently infected cells under LRA treatment. Model analysis showed that, in addition to increasing the immune recognition and clearance of infected cells, the duration of HIV antigen expression (i.e., the period of vulnerability) plays an important role in determining the efficacy of LRAs, especially if effective clearance is achieved. Patients may benefit from pulsatile LRA exposures compared with continuous LRA exposures if the period of vulnerability is long and the clearance rate is high, both in the presence and absence of an LRA. Overall, the model framework serves as a useful tool to evaluate the efficacy and the rational design of LRAs and combination strategies.

Indexed as

Models, BiologicalAnti-HIV AgentsCD4-Positive T-LymphocytesDrug DesignDrug Therapy, CombinationHIV-1HIV AntigensHIV InfectionsHumansPulse Therapy, DrugTreatment OutcomeVirus LatencyAnti-HIV AgentsHIV AntigensAIDS/HIVDrug therapyTherapeutics

Identifiers

PMID30333308
PMCPMC6237475

What OpenQuestion holds

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Registered trials

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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.