Drugs may reach the central nervous system (CNS) poorly. The CNS Penetration Effectiveness (CPE) is a measure of how well a multi-drug regimen reaches the CNS. The authors are from the University of California San Diego, Washington University, University of Texas Galveston, Johns Hopkins University and Mt. Sinai School of Medicine (New York).
Issues pertinent to antiretroviral drug therapy:
(1) An HIV drug regimen consists of multiple drugs.
(2) Prevention and therapy of HIV-associated neurocognitive disorder requires effective control of the viral load in the central nervous system.
Each drug in a regimen can be characterized by how well it gets into the CNS.
Chemical Structure |
Measureable Levels in CSF |
Effect on CSF Viral Loads |
Penetration Category |
good penetration |
at or above levels needed to control |
good |
1 |
fair |
below levels needed to control |
fair |
0.5 |
poor penetration |
none |
poor |
0 |
where:
• Assignment of the penetration category is based on 1 or more of the measures (OR applied).
• If a virus is resistant to a drug then inclusion of the drug in a regimen makes little sense.
• The score ignores synergy and antagonism.
CPE rank for a drug regimen =
= SUM(penetration categories for all drugs in the regimen)
Interpretation:
• minimum CPE rank: 0
• maximum CPE rank: number of drugs in the regimen
• A low CPE rank is associated with higher CNS viral loads and greater risk of a neurocognitive disorder.
• A CPE rank < 2 was associated with higher CSF viral loads.
Purpose: To determine the CNS Penetration Effectiveness (CPE) score for an antiretroviral drug regimen.
Specialty: Pharmacology, clinical
Objective: dosage adjustments, administration
ICD-10: B20-B24, B33.3,