Clinical Pharmacokinetics

, Volume 53, Issue 10, pp 891–906 | Cite as

Pharmacokinetics and Pharmacodynamics of Antiretrovirals in the Central Nervous System

  • Andrea CalcagnoEmail author
  • Giovanni Di Perri
  • Stefano Bonora
Review Article


HIV-positive patients may be effectively treated with highly active antiretroviral therapy and such a strategy is associated with striking immune recovery and viral load reduction to very low levels. Despite undeniable results, the central nervous system (CNS) is commonly affected during the course of HIV infection, with neurocognitive disorders being as prevalent as 20–50 % of treated subjects. This review discusses the pathophysiology of CNS infection by HIV and the barriers to efficacious control of such a mechanism, including the available data on compartmental drug penetration and on pharmacokinetic/pharmacodynamic relationships. In the reviewed articles, a high variability in drug transfer to the CNS is highlighted with several mechanisms as well as methodological issues potentially influencing the observed results. Nevirapine and zidovudine showed the highest cerebrospinal fluid (CSF) to plasma ratios, although target concentrations are currently unknown for the CNS. The use of the composite CSF concentration effectiveness score has been associated with better virological outcomes (lower HIV RNA) but has been inconsistently associated with neurocognitive outcomes. These findings support the CNS effectiveness of commonly used highly antiretroviral therapies. The use of antiretroviral drugs with increased CSF penetration and/or effectiveness in treating or preventing neurocognitive disorders however needs to be assessed in well-designed prospective studies.


Atazanavir Darunavir Raltegravir Maraviroc Etravirine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Conflict of interest

No funding has been received for the preparation of this review.

A. Calcagno has received travel grants or speaker’s honoraria from Abbott, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD) and Janssen-Cilag. S. Bonora has received grants, travel grants and consultancy fees from Abbott, Boehringer-Inghelheim, BMS, Gilead-Sciences, GlaxoSmithKline (GSK), MSD, Pfizer and Janssen-Cilag. G. Di Perri has received grants, travel frants and consultancy fees from Abbott, Boehringer-Inghelheim, BMS, Gilead-Sciences, GSK, MSD, Pfizer, Roche and Tibotec (Johnson & Johnson).


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Andrea Calcagno
    • 1
    Email author
  • Giovanni Di Perri
    • 1
  • Stefano Bonora
    • 1
  1. 1.Unit of Infectious Diseases, Department of Medical SciencesUniversity of TorinoTorinoItaly

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