Human Immunodeficiency Virus (HIV) epidemics remain devastating around the world. Since there is no cure for HIV, preventive therapy has received tremendous attention. To find the immune cells, the primary target of HIV, the virus needs to cross the cervicovaginal mucus (CVM) layer, which acts as a barrier for the virus to move freely. The drug-filled nanoparticles that destroy viruses in CVM are one of the essential preventive therapies. In this study, we develop mathematical models to describe how the virus transports through the CVM and how this transport is affected by the CVM acidity. Since the motion of the virus in the acidic CVM is hindered, accurate modeling is necessary to incorporate hindrance due to adherence in acidic media. We model the temporal dynamics of virus concentration using two model components diffusion, and hindrance where diffusion is modeled using Fick’s law and hindrance is modeled with pH dependency. We will use our model to evaluate the effects of nanoparticle-based therapy on virus distribution and transport across CVM. Our objective is to show that the proper implementation of nanoparticle-based therapy can significantly control virus entry through CVM, thereby avoiding the establishment of HIV infection. Such preventive approaches can help curb the global HIV epidemic.