Penetration and Effectiveness of Antiretroviral Therapy in the Central Nervous System

Letendre, Scott; Ellis, Ronald J.; Best, Brookie; Bhatt, Archana; Marquie-Beck, Jennifer; LeBlanc, Shannon; Rossi, Steven; Capparelli, Edmund; McCutchan, J. Allen
June 2009
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry;Jun2009, Vol. 8 Issue 2, p169
Academic Journal
Combination antiretroviral therapy (ART) has markedly reduced morbidity and mortality among HIV-infected individuals but not the prevalence of HIV-associated neurocognitive disorders (HAND). Several conditions may be responsible for the high prevalence of cognitive impairment, including incomplete suppression of HIV in nervous system by some antiretrovirals. Since individuals with HAND have a lower quality of life, worse medication adherence, and a higher risk of death, optimizing treatment of neurocognitive outcomes is an important goal of therapy. Optimization of ART to treat the CNS is limited, in part, by the ability of many antiretrovirals to cross the blood-brain barrier (BBB). Differences between antiretrovirals in crossing the BBB -- and by extension differences in their concentrations in the brain -- may explain inter-individual differences in susceptibility to HAND among treated individuals. This manuscript reviews relevant data on the CSF pharmacology of antiretrovirals and accumulating evidence that the use of drugs that reach therapeutic concentrations in the CNS are the best options to prevent and treat HIV-induced brain injury. Despite the importance of healthy cognition to the quality of patients' lives, consensus treatment guidelines for HAND have yet to be formulated more than two decades after its first description. Formulating widely accepted recommendations for CNS-optimized treatment strategies requires a level of clinical evidence not yet developed but studies are underway to address this shortcoming.


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