Fri, 24 Jan 2020 00:00:00 GMT-06:00 - Stafford, Kristen A.; Mayer, Bryan T.; Fulp, William; Chua, Joel; Davis, Charles; Gilliam, Bruce; Dong, Dan; Gallo, Robert C.; Sajadi, Mohammad M. Θέμα:
Vaccines and biologics containing CD4 molecules or HIV gp120 might induce antibodies targeting CD4. We evaluated temporal variability of CD4 levels in healthy volunteers to quantify declines that could indicate true adverse events.
Design:
Prospective observational cohort study of 100 healthy adults without HIV infection from the Baltimore region.
Μέθοδοι:
Participants enrolled and consented to blood draws for immunologic lab panels performed once every eight weeks for 48 weeks. The primary CD4+ measurements were CD4+ absolute count (cells/mm3) and CD4 percentage (CD4%, total CD4 cells/total lymphocyte cells). CD4 changes over time were modeled using fold-changes for CD4+ absolute counts and differences for CD4 percentages.
Αποτελέσματα:
Variation of average CD4+ cell counts and percentages were highly participant-specific (p < 0.001 for both). However, changes in both CD4+ measurements over time were stable in the population. We proposed thresholds to flag unusual drops using 1.5 standard deviation estimates, calculated as 1.5-fold declines for CD4+ count 6.4% declines for CD4 percentage. In this healthy cohort, flagging simultaneous declines in both measurements corresponded to a low false-positive rate (5.26%).
Συμπεράσματα:
Normal biological variation in large lymphocytes should be taken into account to establish thresholds for adverse changes in clinical trials. The inherent subject-specific variability in CD4 levels make establishing absolute cutoffs difficult. However, this study proposes that thresholds for declines using 1.5 standard deviations from these data (50% in absolute count and 6.4% for CD4 percentage) allow a small false-positive rate (βΌ5%) that could maintain sensitivity for true adverse events in a clinical trial.
Corresponding author: Mohammad M. Sajadi, MD, Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard Street, Baltimore, Maryland 21201, msajadi@ihv.umaryland.edu
The authors report no conflicts of interest related to this work.
* These authors contributed equally to this manuscript
Funding: This study was funded by the Bill and Melinda Gates Foundation.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
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210-7222222
Υπουργείο Υγείας - Οδηγία Υ1/3239/2000
