title: CSF penetration by antiretroviral drugs.
abstract: Severe HIV-associated neurocognitive disorders (HAND), such as HIV-associated dementia, and opportunistic CNS infections are now rare complications of HIV infection due to comprehensive highly active antiretroviral therapy (HAART). By contrast, mild to moderate neurocognitive disorders remain prevalent, despite good viral control in peripheral compartments. HIV infection seems to provoke chronic CNS injury that may evade systemic HAART. Penetration of antiretroviral drugs across the blood-brain barrier might be crucial for the treatment of HAND. This review identifies and evaluates the available clinical evidence on CSF penetration properties of antiretroviral drugs, addressing methodological issues and discussing the clinical relevance of drug concentration assessment. Although a substantial number of studies examined CSF concentrations of antiretroviral drugs, there is a need for adequate, well designed trials to provide more valid drug distribution profiles. Neuropsychological benefits and neurotoxicity of potentially CNS-active drugs require further investigation before penetration characteristics will regularly influence therapeutic strategies and outcome.
authors.affiliation: Department of Neurology, University of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Eisfeld
authors.forename: Doris
authors.initials: D
authors.lastname: Reichelt
authors.forename: Stefan
authors.initials: S
authors.lastname: Evers
authors.forename: Ingo
authors.initials: I
authors.lastname: Husstedt
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy*; D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000818:Animals; D019380:Anti-HIV Agents / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001812:Blood-Brain Barrier / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans
chemical_list: D019380:Anti-HIV Agents