title: Solving the Blood-Brain Barrier Challenge for the Effective Treatment of HIV Replication in the Central Nervous System.
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.
authors.forename: Luc
authors.initials: L
authors.lastname: Bertrand
authors.forename: Madhavan
authors.initials: M
authors.lastname: Nair
authors.affiliation: University of Miami. Miller School of Medicine, Department of Biochemistry and Molecular Biology, 1011 NW 15th Street, Miami, FL 33136, USA. mtoborek@med.miami.edu.
authors.forename: Michal
authors.initials: M
authors.lastname: Toborek
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000821:virology; D002490:Central Nervous System / Q000187:drug effects* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents