Encyclopedia of AIDS

Living Edition
| Editors: Thomas J. Hope, Douglas Richman, Mario Stevenson

Antiretroviral Drug Penetration into the CNS Compartment

  • Andrea Calcagno
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9610-6_437-1


The central nervous system is reached and infected a few hours after HIV infection. Viral replication occurs in perivascular macrophages, in microglia, and, although restricted, in astrocytes: neuronal damage is believed to be a consequence of neurotoxin production by the aforementioned cells of the immune system. Such cells are reached by antiretroviral drugs either directly (crossing blood–brain and blood–cerebrospinal fluid barriers) or through cerebral extracellular fluid (drained into cerebrospinal fluid); for several drugs, cerebrospinal fluid concentrations have been shown to reflect cerebral interstitial fluid concentrations. The penetration of several compounds into the central nervous system has been shown to be highly variable and to depend on drugs’ (molecular weight, lipophilicity, ionization, plasma protein binding, transport mechanisms) and patients’ characteristics (age, blood flow, blood–brain barrier permeability). Although the exact amount of drug...


Central Nervous System Infection Inhibitory Quotient Cerebrospinal Fluid Barrier Central Nervous System Penetration Effectiveness Central Nervous System Exposure 
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  1. Calcagno A, Simiele M, Alberione MC, et al. Cerebrospinal fluid inhibitory quotients of antiretroviral drugs in HIV-infected patients are associated with compartmental viral control. Clin Infect Dis. 2015;60(2):311–7.CrossRefPubMedGoogle Scholar
  2. Canestri A, Lescure FX, Jaureguiberry S, et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis. 2010;50(5):773–8.CrossRefPubMedGoogle Scholar
  3. Clifford DB, Ances BM. HIV-associated neurocognitive disorder. Lancet Infect Dis. 2013;13(11):976–86.PubMedCentralCrossRefPubMedGoogle Scholar
  4. Cysique LA, Waters EK, Brew BJ. Central nervous system antiretroviral efficacy in HIV infection: a qualitative and quantitative review and implications for future research. BMC Neurol. 2011;11:148.PubMedCentralCrossRefPubMedGoogle Scholar
  5. Dahl V, Peterson J, Fuchs D, et al. Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation. AIDS. 2014;28(15):2251–8.PubMedCentralCrossRefPubMedGoogle Scholar
  6. Edén A, Fuchs D, Hagberg L, et al. HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment. J Infect Dis. 2010;202(12):1819–25.PubMedCentralCrossRefPubMedGoogle Scholar
  7. Eisfeld C, Reichelt D, Evers S, Husstedt I. CSF penetration by antiretroviral drugs. CNS Drugs. 2013;27(1):31–55.CrossRefPubMedGoogle Scholar
  8. Ellis RJ, Letendre S, Vaida F, et al. Randomized trial of central nervous system-targeted antiretrovirals for HIV-associated neurocognitive disorder. Clin Infect Dis. 2014;58(7):1015–22.PubMedCentralCrossRefPubMedGoogle Scholar
  9. Garvey LJ, Pavese N, Politis M, et al. Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART. AIDS. 2014;28(1):67–72.CrossRefPubMedGoogle Scholar
  10. Gannon P, Khan MZ, Kolson DL. Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol. 2011;24(3):275–83.PubMedCentralCrossRefPubMedGoogle Scholar
  11. Hammond ER, Crum RM, Treisman GJ, et al. The cerebrospinal fluid HIV risk score for assessing central nervous system activity in persons with HIV. Am J Epidemiol. 2014;180(3):297–307.PubMedCentralCrossRefPubMedGoogle Scholar
  12. Heaton RK, Franklin Jr DR, Deutsch R, et al. Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study. Clin Infect Dis. 2015;60(3):473–80.CrossRefPubMedGoogle Scholar
  13. Letendre Sl, Mills AM, Tashima KT, et al. ING116070: A Study of the Pharmacokinetics and Antiviral Activity of Dolutegravir in Cerebrospinal Fluid in HIV-1–Infected, Antiretroviral Therapy–Naive Subjects. Clin INfect Dis; 2014;59(7):1032–7.CrossRefGoogle Scholar
  14. Shikuma CM, Nakamoto B, Shiramizu B, et al. Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV. Antivir Ther. 2012;17(7):1233–42.PubMedCentralCrossRefPubMedGoogle Scholar
  15. Valcour V, Chalermchai T, Sailasuta N, et al. Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis. 2012;206(2):275–82.PubMedCentralCrossRefPubMedGoogle Scholar
  16. Valcour VG, Ananworanich J, Agsalda M, et al. HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients. PLoS One. 2013;8(7):e70164.PubMedCentralCrossRefPubMedGoogle Scholar
  17. Varatharajan L, Thomas SA. The transport of anti-HIV drugs across blood-CNS interfaces: summary of current knowledge and recommendations for further research. Antiviral Res. 2009;82(2):A99–109.PubMedCentralCrossRefPubMedGoogle Scholar
  18. Yilmaz A, Price RW, Gisslén M. Antiretroviral drug treatment of CNS HIV-1 infection. J Antimicrob Chemother. 2012;67(2):299–311.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Unit of Infectious Diseases, Department of Medical SciencesUniversity of TorinoTorinoItaly