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Clinical Implications of CNS Penetration of Antiretroviral Drugs

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Abstract

The CNS serves as an important sanctuary site for HIV replication. The presence of HIV in this compartment may contribute to neurological complications in individuals infected with HIV. Understanding the CNS penetration capabilities of available antiretroviral agents may help clinicians to design treatment regimens with neuroprotective effects. Although numerous clinical studies and anecdotal reports have examined CSF antiretroviral drug exposure as a marker of CNS penetration, understanding the clinical relevance of these findings is difficult. Challenges with study design and subject recruitment often limit the investigator’s ability to collect comprehensive data. Upon review of available data, the antiretroviral agents zidovudine, stavudine, lamivudine, nevirapine, efavirenz and indinavir demonstrate consistent penetration into the CSF. Zidovudine-, stavudine-, lamivudine-, didanosine- and protease inhibitor-based regimens also appear to suppress CSF viraemia or improve HIV neurological disease. These agents may be appropriate candidates for neuroprotective antiretroviral treatment regimens. Despite these data, several unanswered questions about the CSF antiretroviral drug exposure-response relationship still remain. Prospective, controlled studies examining this relationship are needed before absolute clinical recommendations are founded.

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Acknowledgements

The authors received grant support (R01 AI33835 and UO1 AI41089) from the National Institutes of Health.

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  1. Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, Minnesota, USA

    Heather E. Wynn & Richard C. Brundage

  2. Antiviral Pharmacology Laboratory, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Campus Box C-238, Denver, Colorado, 80262, USA

    Courtney V. Fletcher

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  1. Heather E. Wynn
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Wynn, H.E., Brundage, R.C. & Fletcher, C.V. Clinical Implications of CNS Penetration of Antiretroviral Drugs. Mol Diag Ther 16, 595–609 (2002). https://doi.org/10.2165/00023210-200216090-00002

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