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Record W4388161805 · doi:10.3390/v15112171

HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing

2023· article· en· W4388161805 on OpenAlexaff
Danielle E. Lyons, Priti Kumar, Nadia R. Roan, Patricia Defechereux, Cédric Feschotte, Ulrike C. Lange, Niren Murthy, Pauline Sameshima, Eric Verdin, Julie A. Ake, Matthew S. Parsons, Avindra Nath, Sara Gianella, Davey M. Smith, Esper G. Kallás, Thomas J. Villa, Richard C. Strange, Betty Mwesigwa, Robert L. Furler O’Brien, Douglas F. Nixon, Lishomwa C. Ndhlovu, Susana T. Valente, Mélanie Ott

Bibliographic record

VenueViruses · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsLakehead University
FundersNational Institute of Allergy and Infectious DiseasesNational Institute on Drug AbuseNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthNational Institutes of HealthNational Cancer InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood Institute
KeywordsProvirusGene silencingLatency (audio)VirologyHuman immunodeficiency virus (HIV)BiologyAntiretroviral therapyMedicineComputational biologyComputer scienceViral loadGeneticsGenomeGeneTelecommunications

Abstract

fetched live from OpenAlex

Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel "block-lock-stop" approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.

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 categoriesInsufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.383
Threshold uncertainty score1.000

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)0.0010.041

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 head0.058
GPT teacher head0.312
Teacher spread0.255 · 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; both teacher heads agree on what is shown here.

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

Citations16
Published2023
Admission routes1
Has abstractyes

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