Efavirenz concentrations in CSF exceed IC50 for wild-type HIV

Area of Science:

• Neuroscience
• Infectious Diseases
• Pharmacology

Background:

• HIV-associated neurocognitive disorders persist despite potent antiretroviral therapy (ART).
• Suboptimal drug distribution into the central nervous system (CNS) may contribute to ongoing viral replication and cognitive decline.
• Understanding antiretroviral drug penetration into the CSF is critical for optimizing HIV treatment strategies.

Purpose of the Study:

• To quantify the penetration of efavirenz, a common ART drug, into the cerebrospinal fluid (CSF).
• To assess whether CSF concentrations of efavirenz are sufficient to inhibit wild-type HIV replication.

Main Methods:

• Observational, multicentre study (CHARTER) involving participants on efavirenz-based ART.
• Paired plasma and CSF samples collected within 1 hour of each other.
• Efavirenz concentrations measured using HPLC or HPLC/mass spectrometry.

Main Results:

• Median efavirenz concentrations were 2145 ng/mL in plasma and 13.9 ng/mL in CSF.
• The CSF/plasma concentration ratio was 0.005.
• The CSF/IC50 ratio was 26, with only two samples below the wild-type HIV IC50.

Conclusions:

• Efavirenz achieves therapeutic concentrations in the CSF, approximately 0.5% of plasma levels.
• These concentrations exceed the IC50 for wild-type HIV, suggesting efficacy in the CNS.
• Efavirenz penetration into the CSF supports its role in managing HIV-associated neurological complications.