Relative contribution of pharmacokinetics and immune signatures to clinical outcomes in patients with HIV-associated cryptococcal meningitis

Stott, K E, Tembo, D, Kajanga, C, Ahmadu, A, Namakhwa, D, Kolamunnage-Dona, R, Sarker, C, Moyo, M, Gondwe, E, Chimang’anga, W, Chasweka, M, Shah, R V, Lawrence, D S, Harrison, T S, Jarvis, J N, Lalloo, David ORCID: https://orcid.org/0000-0001-7680-2200, Hope, W, Mwandumba, H C, Chimphambano, T, Dziwani, E, Kadzilimbile, A, Kateta, S, Kossam, E, Kukacha, C, Lipenga, B, Ndaferankhande, J, Ndalama, M, Shah, R, Singini, A, Zambasa, A, Goodall, J, Lechiile, K, Mawoko, N, Mbangiwa, T, Milburn, J, Mmipi, R, Muthoga, C, Ponatshego, P, Rulaganyang, I, Seatla, K, Tlhako, N, Tsholo, K, April, S, Bekiswa, A, Boloko, L, Bookholane, H, Crede, T, Davids, L, Goliath, R, Hlungulu, S, Hoffman, R, Kyepa, H, Masina, N, Maughan, D, Mnguni, T, Moosa, S, Morar, T, Mpalali, M, Naude, J, Oliphant, I, Sayed, S, Sebesho, L, Shey, M, Swanepoel, L, Banda, T, Chikaonda, T, Chitulo, G, Chiwoko, L, Chome, N, Gwin, M, Kachitosi, T, Kamanga, B, Kazembe, M, Kumwenda, E, Kumwenda, M, Maya, C, Mhango, W, Mphande, C, Msumba, L, Munthali, T, Ngoma, D, Nicholas, S, Simwinga, L, Stambuli, A, Tegha, G, Zambezi, J, Ahimbisibwe, C, Akampurira, A, Alice, A, Cresswell, F, Gakuru, J, Kiiza, D, Kisembo, J, Kwizera, R, Kugonza, F, Laker, E, Luggya, T, Lule, A, Musubire, A, Muyise, R, Namujju, O, Ndyetukira, J, Nsangi, L, Okirwoth, M, Sadiq, A, Tadeo, K, Tukundane, A, Williams, D, Atwine, L, Buzaare, P, Collins, M, Emily, N, Inyakuwa, C, Kariisa, S, Mwesigye, J, Niwamanya, S, Rodgers, A, Rukundo, J, Rwomushana, I, Ssemusu, M, Stead, G, Boyd, K, Gondo, S, Kufa, P, Makaha, E, Moyo, C, Mtisi, T, Mudzingwa, S, Mwarumba, T, Zinyandu, T, Alanio, A, Dromer, F, Sturny-Leclere, A, Griffin, P and Hafeez, S (2025) 'Relative contribution of pharmacokinetics and immune signatures to clinical outcomes in patients with HIV-associated cryptococcal meningitis'. Open Forum Infectious Diseases, Vol 12, Issue 4, ofaf190.

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Abstract

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.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 400 Fluid elements. Plasma. Serum. Blood proteins. Blood protein disorders
Faculty: Department:	Education
Digital Object Identifer (DOI):	https://doi.org/10.1093/ofid/ofaf190
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	30 Apr 2025 09:09
Last Modified:	30 Apr 2025 14:44
URI:	https://archive.lstmed.ac.uk/id/eprint/26530

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