Variability of CD4+ Cell Counts in HIV-1-Uninfected Volunteers Who Are Eligible for a Phase I HIV Vaccine Study.
J Acquir Immune Defic Syndr
; 84(1): 37-44, 2020 05 01.
Article
em En
| MEDLINE
| ID: mdl-31985697
ABSTRACT
OBJECTIVE:
Vaccines and biologics containing CD4 molecules or HIV-1 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-1 infection from the Baltimore region.METHODS:
Participants enrolled and consented to blood draws for immunologic laboratory panels performed once every 8 weeks for 48 weeks. The primary CD4 measurements were CD4 absolute count (cells/mm) 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.RESULTS:
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 SD estimates, calculated as 1.5-fold declines for CD4 count and 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%).CONCLUSIONS:
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 makes establishing absolute cutoffs difficult. However, this study proposes that thresholds for declines using 1.5 SDs from these data (50% in absolute count and 6.4% for CD4 percentage) allow a small false-positive rate (â¼5%) that could maintain sensitivity for true adverse events in a clinical trial.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Vacinas contra a AIDS
/
Soronegatividade para HIV
/
Contagem de Linfócito CD4
Tipo de estudo:
Clinical_trials
/
Observational_studies
Limite:
Humans
País como assunto:
America do norte
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article