Title:Solving the Blood-Brain Barrier Challenge for the Effective Treatment of HIV Replication in the Central Nervous System
Volume: 22
Issue: 35
Author(s): Luc Bertrand, Madhavan Nair and Michal Toborek
Affiliation:
Keywords:
HIV, Blood brain barrier, anti-retroviral drugs, central nervous system, viral reservoir, nanoparticles.
Abstract: Recent decades mark a great progress in the treatment of HIV infection. What
was once a deadly disease is now a chronic infection. However, HIV-infected patients are
prone to develop comorbidities, which severely affect their daily functions. For example, a
large population of patients develop a variety of neurological and cognitive complications,
called HIV associated neurological disorders (HAND). Despite efficient repression of viral
replication in the periphery, evidence shows that the virus can remain active in the central
nervous system (CNS). This low level of replication is believed to result in a progression of
neurocognitive dysfunction in infected individuals. Insufficient viral inhibition in the brain
results from the inability of several treatment drugs in crossing the blood-brain barrier
(BBB) and reaching therapeutic concentrations in the CNS. The current manuscript discusses
several strategies that are being developed to enable therapeutics to cross the BBB,
including bypassing BBB, inhibition of efflux transporters, the use of active transporters
present at the BBB, and nanotechnology. The increased concentration of therapeutics in the
CNS is desirable to prevent viral replication; however, potential side effects of anti-retroviral drugs need also to
be taken into consideration.
