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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/μL. 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/μL 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. [ABSTRACT FROM AUTHOR]

The evenness of an ecological community affects ecosystem structure, functioning and stability, and has implications for biodiversity conservation. In uneven communities, most species are rare while a few dominant species drive ecosystem-level properties. In even communities, dominance is lower, with possibly many species playing key ecological roles. The dominance aspect of evenness can be measured as a decreasing function of the proportion of species required to make up a fixed fraction (e.g., half) of individuals in a community. Here we sought general rules about dominance in ecological communities by linking dominance mathematically to the parameters of common theoretical species-abundance distributions (SADs). We found that if a community’s SAD was log-series or lognormal, then dominance was almost inevitably high, with fewer than 40% of species required to account for 90% of all individuals. Dominance for communities with an exponential SAD was lower but still typically high, with fewer than 40% of species required to account for 70% of all individuals. In contrast, communities with a gamma SAD only exhibited high dominance when the average species abundance was below a threshold of approximately 100. Furthermore, we showed that exact values of dominance were highly scale-dependent, exhibiting non-linear trends with changing average species abundance. We also applied our formulae to SADs derived from a mechanistic community model to demonstrate how dominance can increase with environmental variance. Overall, our study provides a rigorous basis for theoretical explorations of the dynamics of dominance in ecological communities, and how this affects ecosystem functioning and stability. [ABSTRACT FROM AUTHOR]

Immune interventions consisting in repeated injections are broadly used as they are thought to improve the quantity and the quality of the immune response. However, they also raise several questions that remain unanswered, in particular the number of injections to make or the delay to respect between different injections to achieve this goal. Practical and financial considerations add constraints to these questions, especially in the framework of human studies. We specifically focus here on the use of interleukin-7 (IL-7) injections in HIV-infected patients under antiretroviral treatment, but still unable to restore normal levels of CD4+ T lymphocytes. Clinical trials have already shown that repeated cycles of injections of IL-7 could help maintaining CD4+ T lymphocytes levels over the limit of 500 cells/μL, by affecting proliferation and survival of CD4+ T cells. We then aim at answering the question: how to maintain a patients level of CD4+ T lymphocytes by using a minimum number of injections (i.e., optimizing the strategy of injections)? Based on mechanistic models that were previously developed for the dynamics of CD4+ T lymphocytes in this context, we model the process by a piecewise deterministic Markov model. We then address the question by using some recently established theory on impulse control problem in order to develop a numerical tool determining the optimal strategy. Results are obtained on a reduced model, as a proof of concept: the method allows to define an optimal strategy for a given patient. This method could be applied to optimize injections schedules in clinical trials. [ABSTRACT FROM AUTHOR]