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Record W4388625787 · doi:10.1038/s41591-023-02611-1

Viral and host mediators of non-suppressible HIV-1 viremia

2023· article· en· W4388625787 on OpenAlexafffund
Abbas Mohammadi, Behzad Etemad, Xin Zhang, Yijia Li, Gregory J. Bedwell, Radwa Sharaf, Autumn Kittilson, Meghan Melberg, Charles R. Crain, Anna K. Traunbauer, 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, Dominic Dorazio, Peter L. Anderson, Steven G. Deeks, Michael M. Lederman, Sigal Yawetz, Daniel R. Kuritzkes, Mathias Lichterfeld, Scott F. Sieg, Athe Tsibris, Mary Carrington, Zabrina L. Brumme, José Castillo‐Mancilla, Alan Engelman, Gaurav D. Gaiha, Jonathan Z. Li

Bibliographic record

VenueNature Medicine · 2023
Typearticle
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 BCFrederick National Laboratory for Cancer ResearchUniversity of PittsburghDana-Farber Cancer InstituteHarvard University Center for AIDS ResearchHarvard UniversityNational Cancer InstituteCase Western Reserve UniversityBrigham and Women's HospitalNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsViremiaDownregulation and upregulationVirologyBiologyViral loadViral replicationCD8EpigeneticsGeneVirusImmunologyImmune systemGenetics

Abstract

fetched live from OpenAlex

Abstract Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples. We defined proviruses that match plasma HIV-1 RNA sequences as ‘producer proviruses’, and those that did not as ‘non-producer proviruses’. Non-suppressible viremia arose from expanded clones of producer proviruses that were significantly larger than the genome-intact proviral reservoir of ART-suppressed individuals. Integration sites of producer proviruses were enriched in proximity to the activating H3K36me3 epigenetic mark. CD4 + T cells from participants with NSV demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, participants with NSV showed significantly lower HIV-specific CD8 + T cell responses compared with untreated viremic controllers with similar viral loads. We identified potential critical host and viral mediators of NSV that may represent targets to disrupt HIV-1 persistence.

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)0.000
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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.433
Threshold uncertainty score0.739

Codex and Gemma teacher scores by category

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 communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

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 head0.006
GPT teacher head0.282
Teacher spread0.276 · 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 designBench or experimental
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

Citations48
Published2023
Admission routes2
Has abstractyes

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