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Record W4400249054 · doi:10.1038/s41467-024-48985-9

HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy

2024· article· en· W4400249054 on OpenAlexafffund
Guinevere Q. Lee, Pragya Khadka, Sarah N. Gowanlock, Dennis C. Copertino, Maggie C. Duncan, F. Harrison Omondi, Natalie N. Kinloch, Jingo Kasule, Taddeo Kityamuweesi, Paul Buule, Samiri Jamiru, Stephen Tomusange, Aggrey Anok, Zhengming Chen, R. Brad Jones, Ronald M. Galiwango, Steven J. Reynolds, Thomas C. Quinn, Zabrina L. Brumme, Andrew D. Redd, Jessica L. Prodger

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsAIDS VancouverSimon Fraser UniversityWestern University
FundersNHLBI Division of Intramural ResearchNational Institute of Allergy and Infectious DiseasesNew Partnership for Africa's DevelopmentNational Institutes of HealthU.S. Department of Health and Human ServicesCanada Research ChairsDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesGovernment of the United KingdomMichael Smith Health Research BCMassachusetts General HospitalWellcome TrustAlliance for Accelerating Excellence in Science in AfricaAfrican Academy of SciencesCanadian Institutes of Health ResearchWellcomeGovernment of Canada
KeywordsProvirusGenomeRecombinant DNAVirologyBiologyHuman immunodeficiency virus (HIV)Antiretroviral therapyGeneticsGeneViral load

Abstract

fetched live from OpenAlex

The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest.

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)0.001
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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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)0.0010.000

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 head0.015
GPT teacher head0.294
Teacher spread0.279 · 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

Citations15
Published2024
Admission routes2
Has abstractyes

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