Evidence map›Paper›PMID 24005480›Full record

ArticleAIDS (London, England)2013

High multiplicity HIV-1 cell-to-cell transmission from macrophages to CD4+ T cells limits antiretroviral efficacy.

Christopher J A Duncan, Rebecca A Russell, Quentin J Sattentau

Abstract read
In one paragraph

Article in AIDS (London, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 76 citations in OpenAlex.

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  9. Type I interferon receptor (Frontiers in immunology · 2022
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  16. Article
  17. Efficient HIV-1Open forum infectious diseases · 2019
    Article
  18. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Christopher J A DuncanSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Rebecca A Russell
Quentin J Sattentau
University of Oxford · GB

Funding

Medical Research Council G0400453Medical Research Council G0901732Wellcome Trust 094449Wellcome Trust 094449/Z/10/Z
6 · The paper itself

Abstract

objectiveFew studies have examined the efficacy of antiretroviral therapy (ART) in the context of cell-to-cell transmission. We aimed to determine whether the activity of ART is limited by the mode of HIV-1 spread between cells and the type of immune cell implicated in transmission, or is independent of these variables.

designART activity was evaluated in primary cells using in-vitro cell-free and cell to-cell HIV-1 infection systems.

methodsHIV-1 cell-free or cell-to-cell transmission between infected monocyte-derived macrophages (MDMs) and autologous target CD4+ T cells was measured in the presence or absence of reverse transcriptase and integrase inhibitors. Viral infection was evaluated using luciferase-reporter infectious molecular HIV-1 clones carrying macrophage-tropic envelope glycoproteins (Envs). Cell-free HIV-1 was titrated to yield different multiplicities of CD4+ T-cell infection.

resultsWhereas cell-free infection of CD4+ T cells was substantially reduced by all inhibitors, cell-to-cell spread from macrophages to CD4+ T cells was largely resistant to inhibition. However, when multiplicity of infection was controlled for, we observed no difference in antiretroviral inhibition of cell-to-cell or cell-free infection.

conclusionCell-to-cell spread of HIV-1 reduces the probability of antiretroviral inhibition, but it is the number of infectious viruses transferred between cells rather than the specific mode of viral spread or transmitting cell type that governs antiretroviral activity. High multiplicity infection in vivo is more likely to occur by cell-to-cell transmission, and these data will inform use of ART against viral reservoirs.

Indexed as

Anti-Retroviral AgentsCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesHIV-1HumansMacrophagesAnti-Retroviral Agents

Identifiers

PMID24005480
PMCPMC4714465
OpenAlexW1992366636

What OpenQuestion holds

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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.