HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

Adaptive protocols based on predictions from a mechanistic model of the effect of IL7 on CD4 counts

Abstract : In human immunodeficiency virus-infected patients, antiretroviral therapy suppresses the viral replication, which is followed in most patients by a restoration of CD4+ T cells pool. For patients who fail to do so, repeated injections of exogenous interleukin 7 (IL7) are experimented. The IL7 is a cytokine that is involved in the T cell homeostasis and the INSPIRE study has shown that injections of IL7 induced a proliferation of CD4+ T cells. Phase I/II INSPIRE 2 and 3 studies have evaluated a protocol in which a first cycle of three IL7 injections is followed by a new cycle at each visit when the patient has less than 550 CD4 cells/í µí¼‡L. Restoration of the CD4 concentration has been demonstrated, but the long-term best adaptive protocol is yet to be determined. A mechanistic model of the evolution of CD4 after IL7 injections has been developed, which is based on a system of ordinary differential equations and includes random effects. Based on the estimation of this model, we use a Bayesian approach to forecast the dynamics of CD4 in new patients. We propose four prediction-based adaptive protocols of injections to minimize the time spent under 500 CD4 cells/í µí¼‡L for each patient, without increasing the number of injections received too much. We show that our protocols significantly reduce the time spent under 500 CD4 over a period of two years, without increasing the number of injections. These protocols have the potential to increase the efficiency of this therapy.
Document type :
Journal articles
Complete list of metadata

Cited literature [45 references]  Display  Hide  Download

https://hal.inria.fr/hal-03161958
Contributor : Laura Villain Connect in order to contact the contributor
Submitted on : Tuesday, January 8, 2019 - 10:55:48 AM
Last modification on : Tuesday, April 26, 2022 - 3:11:24 AM
Long-term archiving on: : Tuesday, April 9, 2019 - 3:18:45 PM

File

adaptive-protocols.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Laura Villain, Daniel Commenges, Chloé Pasin, Mélanie Prague, Rodolphe Thiébaut. Adaptive protocols based on predictions from a mechanistic model of the effect of IL7 on CD4 counts. Statistics in Medicine, Wiley-Blackwell, 2018, 38 (2), pp.221-235. ⟨10.1002/sim.7957⟩. ⟨hal-03161958v2⟩

Share

Metrics

Record views

45

Files downloads

247