Related Experiment Video
Updated: Jun 12, 2026

Sequencing of Bacterial Microflora in Peripheral Blood: our Experience with HIV-infected Patients
Published on: June 11, 2011
Relative Contribution of Pharmacokinetics and Immune Signatures to Clinical Outcomes in Patients With HIV-associated
Katharine E Stott1,2, Dumizulu Tembo2, Cheusisime Kajanga2
1Antimicrobial Pharmacodynamics and Therapeutics group, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Background:
Host immune responses to HIV-associated cryptococcal meningitis are critical in disease outcome. Their interaction with antifungal drug exposure is poorly understood. This study explored associations between immune biomarkers, antifungal drug exposure, and clinical outcomes in HIV-associated cryptococcal meningitis.
Methods:
We analyzed serial plasma and cerebrospinal fluid immune biomarkers from 64 participants recruited from the AMBITION-cm trial. We estimated individual-level exposure to amphotericin B, flucytosine, and fluconazole. Associations between immune biomarkers, pharmacokinetic parameters, and clinical outcomes were evaluated.
Results:
An inflammatory cerebrospinal fluid response, characterized by coordination between tumor necrosis factor-α, granulocyte colony-stimulating factor, and interleukin-7 signaling, was linked to low fungal burden, low intracranial pressure, and survival. However, the value of specific immune biomarkers did not predict EFA or mortality. Exposure to amphotericin B was significantly associated with EFA.
Conclusions:
Favorable clinical outcomes from HIV-associated cryptococcal meningitis are associated with coordinated inflammatory and cytotoxic responses in the central nervous system. Antifungal drug exposure was the dominant predictor of EFA.
Related Concept Videos
Measurement of Bioavailability: Pharmacodynamic Methods
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacokinetic–Pharmacodynamic Relationship: Exposure, Response and Effect
Pharmacokinetic–Pharmacodynamic Relationship: Problems
Cryptococcal Meningitis

