Trial reportThe Journal of clinical investigation2021
CMV viral load kinetics as surrogate endpoints after allogeneic transplantation.
Trial report in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Mathematical Modeling of Within-Host, Untreated, Cytomegalovirus Infection Dynamics after Allogeneic Transplantation.Viruses · 2021Trial
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Human Cytomegalovirus Infection in Haematopoietic Stem Cell Transplant Recipients and CAR T Cell Recipients - PART 1: Risk Factors, Clinical Impact and Immune Response.Reviews in medical virology · 2026Review
- Immune reconstitution and infections with ATG versus post-transplant cyclophosphamide as GvHD prophylaxis after nonmyeloablative matched unrelated donor hematopoietic stem cell transplantation.Frontiers in immunology · 2026Article
- Cytomegalovirus Viral Load Continues to Predict Poor Outcomes in Adults and Children Despite Improved Hematopoietic Cell Transplantation Success.Open forum infectious diseases · 2025Article
- Allogeneic Transplant for CMML.Current hematologic malignancy reports · 2025Review
- Article
- Pharmacokinetic/Pharmacodynamic Modelling and Monte Carlo Simulations to Predict Cytomegalovirus Viral Load in Pediatric Transplant Recipients Treated with (val)Ganciclovir.Clinical pharmacokinetics · 2025Article
- Understanding the Clinical Significance of Cytomegalovirus Viremia After Chimeric Antigen Receptor T-Cell Therapy: Should We be Treating a Value?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- CMV reactivation during pretransplantation evaluation: a novel risk factor for posttransplantation CMV reactivation.Blood advances · 2024Article
- Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses.JCI insight · 2024Article
- Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses.medRxiv : the preprint server for health sciences · 2024Article
- Early T-cell reconstitution predicts risk of EBV reactivation after allogeneic hematopoietic stem cell transplantation.Clinical and experimental medicine · 2024Article
- The Ten Most Common Questions on Cytomegalovirus Infection in Hematopoietic Stem Cell Transplant Patients.Clinical hematology international · 2023Review
- Viral load kinetics and the clinical consequences of cytomegalovirus in kidney transplantation.Frontiers in immunology · 2023Article
- Artificial Intelligence and Machine Learning Based Prediction of Viral Load and CD4 Status of People Living with HIV (PLWH) on Anti-Retroviral Treatment in Gedeo Zone Public Hospitals.International journal of general medicine · 2023Article
- Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation.Clinical & translational immunology · 2023Article
- Impact of Letermovir Primary Cytomegalovirus Prophylaxis on 1-Year Mortality After Allogeneic Hematopoietic Cell Transplantation: A Retrospective Cohort Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- The Impact of High CMV Viral Load and Refractory CMV Infection on Pediatric HSCT Recipients with Underlying Non-Malignant Disorder.Journal of clinical medicine · 2022Article
- High Monocyte Count Associated with Human Cytomegalovirus Replication In Vivo and Glucocorticoid Therapy May Be a Hallmark of Disease.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUNDViral load (VL) surrogate endpoints transformed development of HIV and hepatitis C therapeutics. Surrogate endpoints for CMV-related morbidity and mortality could advance development of antiviral treatments. Although observational data support using CMV VL as a trial endpoint, randomized controlled trials (RCTs) demonstrating direct associations between virological markers and clinical endpoints are lacking.METHODSWe performed CMV DNA PCR on frozen serum samples from the only placebo-controlled RCT of ganciclovir for early treatment of CMV after hematopoietic cell transplantation (HCT). We used established criteria to assess VL kinetics as surrogates for CMV disease or death by weeks 8, 24, and 48 after randomization and quantified antiviral effects captured by each marker. We used ensemble-based machine learning to assess the predictive ability of VL kinetics and performed this analysis on a ganciclovir prophylaxis RCT for validation.RESULTSVL suppression with ganciclovir reduced cumulative incidence of CMV disease and death for 20 years after HCT. Mean VL, peak VL, and change in VL during the first 5 weeks of treatment fulfilled the Prentice definition for surrogacy, capturing more than 95% of ganciclovir's effect, and yielded highly sensitive and specific predictions by week 48. In the prophylaxis trial, the viral shedding rate satisfied the Prentice definition for CMV disease by week 24.CONCLUSIONSOur results support using CMV VL kinetics as surrogates for CMV disease, provide a framework for developing CMV preventative and therapeutic agents, and support reductions in VL as the mechanism through which antivirals reduce CMV disease.FUNDINGMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.