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The "shock and kill" strategy is being widely explored to purge Human Immunodeficiency Virus (HIV) latent reservoirs. Romidepsin, a kind of latency-reversing agents (LRAs), has been shown to induce HIV RNA transcription. However, several clinical trials testing this drug have resulted in limited effect in reducing the HIV latent reservoirs. To understand the mechanisms underlying such limited effect, we develop a multi-scale model that incorporates pharmacokinetics and considers the toxicity of romidepsin to T cells in this paper. By fitting the model to the viral load data from plasma of six patients received romidepsin, we find that the model with T cell toxicity of romidepsin can well explain the clinical data. The dynamics of latently infected cells during romidepsin administration are explored using the best-fit parameter values. The results show that latently infected cells decrease very slowly and remain very stable overall in four of the six participants under the assumption of T cell toxicity of romidepsin. This implies that the ineffectiveness of romidepsin on latent reservoirs can be explained by its toxicity to T cells. In the remaining two participants, however, latently infected cells are quite stable without T cell toxicity of LRAs. It is found that the estimated activation rate of latently infected cells by romidepsin and the estimated elimination rate of romidepsin on immune cells for these two patients are very different from those for the other four patients. Thus we speculate that the heterogeneous response to romidepsin across participants may also be a determining factor of the effectiveness of romidepsin. These results may have significant implications in the search for the control of HIV infection. • An HIV model is proposed to understand the cause of ineffectiveness of romidepsin in the "shock and kill" strategy. • The model has a good fit to patients' data when T cell toxicity of romidepsin is considered. • The toxicity of romidepsin to T cell may contribute to the ineffectiveness of "shock and kill" strategy concerning romidepsin. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, a delayed differential equation model that describes HIV infection of CD4+ T cells is considered. The stability of the positive equilibrium and the existence of Hopf bifurcation are investigated. In succession, using the normal form theory and center manifold argument, we derive the explicit formulas which determine the stability, direction and other properties of bifurcating periodic solutions. [Copyright &y& Elsevier]

This paper proposes and analyzes an adaptive immunity HIV infection model. The model describes the interaction between healthy CD 4 + T cells, silent (latent) infected cells, active infected cells, free HIV particles, Cytotoxic T lymphocytes (CTLs) and antibodies. The healthy CD 4 + T cells can be infected when they are contacted by one of the following: (i) free HIV particles, and this is known as virus-to-cell (VTC) transmission (ii) silent infected cells, and we call this mode of infection as silent HIV-infected cell-to-cell (CTC) transmission, and (iii) active infected cells, and we call this mechanism active HIV-infected CTC transmission. The incidence rates of the healthy CD 4 + T cells with free HIV particles, silent infected cells, and active infected cells are given by general functions. Moreover, the production/proliferation and removal/death rates of all compartments are represented by general functions. The model is an improvement of the existing HIV infection models which have neglected the incidence between the silent infected cells and healthy CD 4 + T cells. We first show that the model is well-posed. Then, we show that the model has five equilibria and their existence are governed by five threshold parameters. Under a set of conditions on the general functions and the threshold parameters, we have proven the global asymptotic stability of all equilibria by using Lyapunov's method. We have illustrated the theoretical results via numerical simulations. We have studied the effect of CTC transmission on the dynamical behavior of the system. We have shown that inclusion of CTC transmission decreases the concentration of the healthy CD4 + T cells and increases the concentrations of the infected cells and free HIV particles. [ABSTRACT FROM AUTHOR]