Stott, Katharine E 
ORCID: 0000-0001-7079-7957, Tembo, Dumizulu, Kajanga, Cheusisime, Ahmadu, Ajisa, Namakhwa, Dumisan, Kolamunnage-Dona, Ruwanthi ORCID: 0000-0003-3886-6208, Sarker, Chandni ORCID: 0009-0007-0786-3422, Moyo, Melanie ORCID: 0000-0002-0483-4817, Gondwe, Ebbie, Chimang'anga, Wezi et al (show 9 more authors)
(2025)
Relative Contribution of Pharmacokinetics and Immune Signatures to Clinical Outcomes in Patients With HIV-associated Cryptococcal Meningitis.
Open forum infectious diseases, 12 (4).
ofaf190-.
ISSN 2328-8957, 2328-8957
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AMBITION Study Group |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Population Health Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 May 2025 08:58 |
| Last Modified: | 06 Aug 2025 02:38 |
| DOI: | 10.1093/ofid/ofaf190 |
| Open Access URL: | https://doi.org/10.1093/ofid/ofaf190 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3192678 |
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