OA3-3 Anti-PD-1 disrupts HIV latency in non-proliferating but not in proliferating T cells
Bibliographic record
Abstract
the new standard of care for second-line treatment of advanced non-small cell lung cancer (NSCLC).The question of whether anti-PD-1 could be a tool for HIV-cure is still pending.Here we report for the first time the clinical experience in 12 HIV-infected patients treated with the anti-PD-1 antibody nivolumab, and the detailed immunovirological evolution in one patient with lung cancer.Methods: Twelve HIV-infected patients (10 male, 1 female, 1 transgender) received nivolumab as a second line therapy for NSCLC (n=11) or melanoma (n=1).Ultrasensitive plasma viral load (US-VL), HIV-cell associated DNA, phenotypic and functional T cell analysis, intracellular-cytokine-staining assay against 15-mer HIV peptides, and plasma IL-6 levels were quantified at all time points (D0, D14, D30, D60, D120) in one patient.Results: In the 12 patients, best tumoral response was partial response (n=3), stability (n=5), or progression (n=4).All plasma HIV viral load were undetectable at D0, and no viral rebound was further observed.CD4 and CD8 cell counts were slightly modified upon nivolumab in only 5/12 patients (median 338 and 674/mm3 at D0; 351 and 525/mm3 after 3 or 4 nivolumab injections).In one patient, US-VL was undetectable and stable, but a slight 2-fold increase in HIV-cell associated DNA levels was observed (116 at D0 vs 213 copies/106 PBMC at D30).IL-6 plasma levels peaked at D14 (539 pg/mL) and returned to normal beyond D60.PD-1 and LAG3 expression on total CD4 and CD8 T cells decreased at D30. PD-1 expression remained low at D120 whereas LAG3 expression returned to D0 level.HIV-specific IFNγ+CD8+ cells increased from 0.1% at D0 to 0.4% at D30.Finally, the total transitional-memory (CD8+CCR7-CD27+CD45RA-, TM) CD8 population increased (+64%) while the RA-re-expressing effector-memory cells decreased (-41%) at D120.Conclusions: Our data suggest that nivolumab is well tolerated in HIV-infected patients, is successful at enhancing the capacities of HIV-specific CD8 TM cells to proliferate and to secrete cytokines, expanding the PD-1low T cell subset, with no or little impact on HIV replication or reservoirs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".