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Record W4402384263 · doi:10.1038/s41392-024-01943-9

Anti-PD-L1 antibody ASC22 in combination with a histone deacetylase inhibitor chidamide as a “shock and kill” strategy for ART-free virological control: a phase II single-arm study

2024· article· en· W4402384263 on OpenAlexaff
Luling Wu, Zhihang Zheng, Jingna Xun, Li Liu, Jiangrong Wang, Xinyu Zhang, Yueming Shao, Yinzhong Shen, Renfang Zhang, Min Zhang, Meiyan Sun, Tangkai Qi, Zhenyan Wang, Shuibao Xu, Weihong Song, Yang Tang, Bihe Zhao, Zichen Song, Jean‐Pierre Routy, Hongzhou Lu, Jun Chen

Bibliographic record

VenueSignal Transduction and Targeted Therapy · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsMcGill University Health Centre
Fundersnot available
KeywordsCD8Histone deacetylase inhibitorAntibodyImmunologyViral loadBiologyImmunityMedicineHuman immunodeficiency virus (HIV)VirologyInternal medicineImmune systemHistone deacetylaseHistoneDNA

Abstract

fetched live from OpenAlex

Abstract The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8 + T cells (NCT05129189). 15 participants completed the study. At week 8, CA HIV RNA levels showed a significant increase from baseline, and the values returned to baseline after discontinuing ASC22 and chidamide. The total HIV DNA was only transiently increased at week 4 ( P = 0.014). In contrast, integrated HIV DNA did not significantly differ from baseline. Increases in the proportions of effector memory CD4 + and CD8 + T cells (T EM ) were observed from baseline to week 24 ( P = 0.034 and P = 0.002, respectively). The combination treatment did not succeed in enhancing the function of HIV Gag/Pol- specific CD8 + T cells. Nevertheless, at week 8, a negative correlation was identified between the proportions of HIV Gag-specific T EM cells and alterations in integrated DNA in the T cell function improved group ( P = 0.042 and P = 0.034, respectively). Nine adverse events were solicited, all of which were graded 1 and resolved spontaneously. The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs. Further investigations are warranted in the context of analytic treatment interruption.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.613
Threshold uncertainty score0.770

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)0.0000.000

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 head0.021
GPT teacher head0.309
Teacher spread0.288 · 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

Citations12
Published2024
Admission routes1
Has abstractyes

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