学术文献库

HIV-1 affects tens of millions of people worldwide. Current treatments often involve a cocktail of antiretroviral drugs, which are effective in reducing the virus and extending life spans. However, there is currently no FDA-approved HIV-1 transcription inhibitor. Furthermore, there have only been a few attempts to model the transcription process in HIV-1. In this work, we extend a novel three-state model of HIV-1 transcription introduced in DeMarino et al. (2020) that has been developed and validated against experimental data. After fitting this model to in vitro data, significant differences in the transcription process of HIV-1 in T-cells and macrophages have been observed. In particular, the activation of the HIV-1 promoter in T-cells appears to take place rapidly as the Tat protein approaches a critical threshold. In contrast, the same process occurs smoother in macrophages. In this work, we carry out systematic mathematical analyses of the model to complement experimental data fitting and sensitivity analysis performed earlier. We derive explicit solutions of the model to obtain exact transcription process decay rates for the original model and then study the effect of nonlinearity on the system behavior, including the existence and the local and global stability of the positive equilibrium. We were able to show the stability of the positive steady state in limiting cases, with the global stability in the general case remaining an open question. By modeling the effect of transcription-inhibiting drug therapy, we provide a nontrivial condition for it to be effective in reducing viral load. Moreover, our numerical simulations and analysis point out that the effect of the transcription-inhibitor can be enhanced by synchronizing with standard treatments, such as combination antiretroviral therapy, to allow the reduction of total dosages and toxicity.