Cytomegalovirus (CMV)-Specific Cell-Mediated Immunity for Prediction of Postprophylaxis CMV Disease in a Phase 3 Trial of Letermovir Versus Valganciclovir Prophylaxis in Donor CMV-Seropositive/Recipient CMV-Seronegative Kidney Transplant Recipients
Bibliographic record
Abstract
BACKGROUND: QuantiFERON-cytomegalovirus (QFT-CMV) is a standardized assay for the evaluation of cytomegalovirus-specific cell-mediated immunity (CMV-CMI). OBJECTIVES: The purpose of this study was to assess the evolution of CMV-CMI posttransplant and the clinical utility of QFT-CMV for the prediction of postprophylaxis CMV disease in CMV-seronegative recipients of CMV-seropositive donor kidneys (D+R- KTRs). METHODS: 601 adult CMV D+R- kidney transplant recipients (KTRs) received letermovir or valganciclovir prophylaxis for 28 weeks in a phase 3, double-blind, multicenter trial (ClinicalTrials.gov NCT03443869). QFT-CMV was performed at a central laboratory by masked personnel at transplant, 12, 28, and 52 weeks posttransplant. Investigators assessed CMV disease through week 52. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) at week 28 were used to evaluate the clinical utility of QFT-CMV. RESULTS: Positive QFT-CMV results (pooled) were detected: baseline-1.2%, week 12-2.6%, week 28-7.7%, and week 52-28.9%. The distribution of positive results with letermovir and valganciclovir was comparable, except at week 28 (letermovir 2.2% and valganciclovir 12.8%). Postprophylaxis CMV disease by week 52 occurred in 18.3% (84/460) of evaluable participants: 12.5% (4/32) of participants with a positive, 17.5% (66/377) with a negative, and 27.5% (14/51) with an indeterminate result at week 28 (p = not significant for all comparisons). QFT-CMV sensitivity, specificity, PPV, and NPV were 8.3%, 94.3%, 87.5%, and 17.5%, and were similar when pooling indeterminate and negative results and within the letermovir and valganciclovir study arms. CONCLUSIONS: Among adult CMV high-risk D+R- KTRs who received prophylaxis, CMV-CMI by QFT-CMV increased over time. The result at the end of prophylaxis had limited clinical utility for identifying the risk for subsequent CMV disease.
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
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".