P-Glycoprotein’s Role in Anti-Retroviral Drug Delivery Across the Blood-Brain Barrier To Combat Human Immunodeficiency Virus (HIV)

Abstract

HIV continues to be a significant worldwide public health concern, with millions of deaths to date and ongoing transmission in all countries. It is challenging to cure because the virus remains within stable reservoirs that evade detection by the immune system. While the available treatments for HIV are effective, there are many options that have poor penetration across the BBB (blood-brain barrier). Treating the infected immune cells found in the CNS (central nervous system) is a challenge because patients are able to have undetectable viral load tests in the blood despite having dormant HIV reservoirs elsewhere in the body. This leads to a chance for these individuals with HIV to experience a range of cognitive, motor, and/or mood issues referred to as HIV-Associated Neurocognitive Disorder (HAND). However, as shown in Figure 1, the context of awakening these reservoirs using a Trojan horse-like method specifically targeting P-glycoprotein (P-gp) in the BBB, an efflux transporter, may provide important insight into decreasing the incidence of HAND. This diagram illustrates the typical situation of an HIV-infected person receiving treatment and the role of P-gp in preventing the drug from penetrating the BBB. The diagram is adapted from Al Rihani, Sweilem B., et al. "Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level." International Journal of Molecular Sciences 22.7 (2021): 3742. Print.