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Record W2957711757 · doi:10.1016/j.xcrm.2020.100096

Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection

2019· preprint· en· W2957711757 on OpenAlexafffund
Sean M. Hughes, Claire Levy, Joanne D. Stekler, Urvashi Pandey, Lucia Vojtech, Alicia R. Berard, Kenzie Birse, Laura Noël‐Romas, Brian Richardson, Jackelyn B. Golden, Michael Cartwright, Ann C. Collier, Claire E. Stevens, Marcel E. Curlin, Timothy H. Holtz, Nelly Mugo, Elizabeth Irungu, Elly Katabira, Timothy R. Muwonge, Javier R. Lama, Jared M. Baeten, Adam Burgener, Jairam R. Lingappa, M. Juliana McElrath, Romel D. Mackelprang, Ian McGowan, Ross Cranston, Mark J. Cameron, Florian Hladik

Bibliographic record

VenueCell Reports Medicine · 2019
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversity of ManitobaPublic Health Agency of Canada
FundersNational Institute on AgingJanssen BiotechCanadian Institutes of Health ResearchCenters for Disease Control and PreventionNational Cancer InstituteNational Institutes of HealthJames B. Pendleton Charitable TrustMerckBill and Melinda Gates FoundationNational Institute of Diabetes and Digestive and Kidney DiseasesJanssen PharmaceuticalsGilead SciencesNational Institute of Allergy and Infectious Diseases
KeywordsDuodenumGastrointestinal tractMedicineInterferonBiopsyRectumImmune systemIntestinal mucosaInternal medicineImmunology

Abstract

fetched live from OpenAlex

Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are used for HIV treatment and prevention. Previously, we found that topical rectal tenofovir gel caused immunological changes in the mucosa. Here, we assess the effect of oral TDF/FTC in three HIV pre-exposure prophylaxis trials, two with gastrointestinal and one with cervicovaginal biopsies. TDF/FTC induces type I/III interferon-related (IFN I/III) genes in the gastrointestinal tract, but not blood, with strong correlations between the two independent rectal biopsy groups (Spearman r = 0.91) and between the rectum and duodenum (r = 0.81). Gene set testing also indicates stimulation of the type I/III pathways in the ectocervix and of cellular proliferation in the duodenum. mRNA sequencing, digital droplet PCR, proteomics, and immunofluorescence confirm IFN I/III pathway stimulation in the gastrointestinal tract. Thus, oral TDF/FTC stimulates an IFN I/III signature throughout the gut, which could increase antiviral efficacy but also cause chronic immune activation in HIV prevention and treatment settings.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.070
Threshold uncertainty score0.929

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.020
GPT teacher head0.280
Teacher spread0.260 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2019
Admission routes2
Has abstractyes

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