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Record W4361864049 · doi:10.1101/2023.03.30.23287124

Viral and Host Mediators of Non-Suppressible HIV-1 Viremia

2023· preprint· en· W4361864049 on OpenAlexafffund
Abbas Mohammadi, Behzad Etemad, Xin Zhang, Yijia Li, Gregory J. Bedwell, Radwa Sharaf, Autumn Kittilson, Meghan Melberg, Colline Wong, Jesse Fajnzylber, Daniel Worrall, Alex Rosenthal, Hannah Jordan, Nikolaus Jilg, Clarety Kaseke, Françoise Giguel, Xiaodong Lian, Rinki Deo, Elisabeth Gillespie, Rida Chishti, Sara Abrha, Taylor Adams, Abigail Siagian, Peter L. Anderson, Steven G. Deeks, Michael M. Lederman, Sigal Yawetz, Daniel R. Kuritzkes, Mathias Lichterfeld, Athe Tsibris, Mary Carrington, Zabrina L. Brumme, José Castillo‐Mancilla, Alan Engelman, Gaurav D. Gaiha, Jonathan Z. Li

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsAIDS VancouverSimon Fraser University
FundersNational Institute of Allergy and Infectious DiseasesCenter for AIDS Research, University of WashingtonMichael Smith Health Research BCHarvard University Center for AIDS ResearchHarvard UniversityFrederick National Laboratory for Cancer ResearchGilead SciencesNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsViremiaDownregulation and upregulationVirologyBiologyViral loadGene silencingInterferonCD8EpigeneticsGeneViral replicationImmunologyHuman immunodeficiency virus (HIV)VirusImmune systemGenetics

Abstract

fetched live from OpenAlex

Abstract Non-suppressible HIV-1 viremia (NSV) can occur in persons with HIV despite adherence to combination antiretroviral therapy (ART) and in the absence of significant drug resistance. Here, we show that plasma NSV sequences are comprised primarily of large clones without evidence of viral evolution over time. We defined proviruses that contribute to plasma viremia as “producer”, and those that did not as “non-producer”. Compared to ART-suppressed individuals, NSV participants had a significantly larger producer reservoir. Producer proviruses were enriched in chromosome 19 and in proximity to the activating H3K36me3 epigenetic mark. CD4 + cells from NSV participants demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, NSV participants showed no elevation in HIV-specific CD8 + cell responses and producer proviruses were enriched for HLA escape mutations. We identified critical host and viral mediators of NSV that represent potential targets to disrupt HIV persistence and promote viral silencing.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.018
GPT teacher head0.280
Teacher spread0.262 · 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 source (direct Gemma or distilled Codex), 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

Citations6
Published2023
Admission routes2
Has abstractyes

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