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Several strategies are currently investigated to reduce the pool of all HIV-1 reservoirs in infected patients in order to achieve functional cure. The most prominent HIV-1 cell reservoirs in the brain are microglial cells. Virus infection maybe lifelong. Infected microglial cells are believed to be the source of peripheral tissues reseeding and responsible for the emergence of drug resistance. Clearing infected cells from the brain is therefore crucial. However, many characteristics of microglial cells and the central nervous system prevent the eradication of brain reservoirs. Current trials, such as “shock and kill”, the “deep and lock” and the gene editing strategies do not respond to these difficulties. Therefore, new strategies have to be designed when considering brain reservoirs such as microglial cells. We set up an original gene suicide strategy using a latently infected microglial model. In this paper we provide proof of concept of this strategy. Our results demonstrate that this strategy enables the eradication of latently-infected microglial cells.

In adherent individuals, antiretroviral therapy (ART) suppresses HIV replication, restores immune function, and prevents the development of AIDS. However, ART is not curative and has to be followed lifelong. Persistence of viral reservoirs forms the major obstacle to an HIV cure. HIV latent reservoirs persist primarily by cell longevity and proliferation, but replenishment by residual virus replication despite ART has been proposed as another potential mechanism of HIV persistence. It is a matter of debate whether different ART regimens are equally potent in suppressing HIV replication. Here, we summarized the current knowledge on the role of ART regimens in HIV persistence, focusing on differences in residual plasma viremia and other virological markers of the HIV reservoir between infected individuals treated with combination ART composed of different antiretroviral drug classes.

This paper studies the global stability of two discrete-time HIV infection models. The models integrate (i) latently infected cells, (ii) long-lived chronically infected cells and (iii) short-lived infected cells. The second model generalizes the first one by assuming that the incidence rate of infection as well as the production and removal rates of the HIV particles and cells are modeled by general nonlinear functions. We discretize the continuous-time models by using a nonstandard finite difference scheme. The positivity and boundedness of solutions are established. The basic reproduction number is derived. By using the Lyapunov method, we prove the global stability of the models. Numerical simulations are presented to illustrate our theoretical results.

In this paper, we construct an Human immunodeficiency virus (HIV) dynamics model with impairment of B-cell functions and the general incidence rate. We incorporate three types of infected cells, (i) latently-infected cells, which contain the virus, but do not generate HIV particles, (ii) short-lived productively-infected cells, which live for a short time and generate large numbers of HIV particles, and (iii) long-lived productively-infected cells, which live for a long time and generate small numbers of HIV particles. The model considers five distributed time delays to characterize the time between the HIV contact of an uninfected CD4 + T-cell and the creation of mature HIV. The nonnegativity and boundedness of the solutions are proven. The model admits two equilibria, infection-free equilibrium E P 0 and endemic equilibrium E P 1 . We derive the basic reproduction number R 0 , which determines the existence and stability of the two equilibria. The global stability of each equilibrium is proven by utilizing the Lyapunov function and LaSalle&rsquo, s invariance principle. We prove that if R 0 &lt, 1 , then E P 0 is globally asymptotically stable, and if R 0 &gt, 1 , then E P 1 is globally asymptotically stable. These theoretical results are illustrated by numerical simulations. The effect of impairment of B-cell functions, time delays, and antiviral treatment on the HIV dynamics are studied. We show that if the functions of B-cells are impaired, then the concentration of HIV is increased in the plasma. Moreover, we observe that the time delay has a similar effect to drug efficacy. This gives some impression for developing a new class of treatments to increase the delay period and then suppress the HIV replication.