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DC Field | Value | Language |
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dc.contributor.author | LallooI, Umesh G. | - |
dc.contributor.author | Komarow, Lauren | - |
dc.contributor.author | AbergI, Judith A. | - |
dc.contributor.author | Clifford, David B. | - |
dc.contributor.author | Hogg, Evelyn | - |
dc.contributor.author | McKhann, Ashley | - |
dc.contributor.author | Bukuru, Aggrey | - |
dc.contributor.author | Pillay, Sandy | - |
dc.contributor.author | Mave, Vidya | - |
dc.contributor.author | Supparatpinyo, Khuanchai | - |
dc.contributor.author | Samaneka, Wadzanai | - |
dc.contributor.author | Langat, Deborah | - |
dc.contributor.author | Ticona, Eduardo | - |
dc.contributor.author | Badal-Faesen, Sharlaa | - |
dc.date.accessioned | 2024-05-09T13:29:25Z | - |
dc.date.available | 2024-05-09T13:29:25Z | - |
dc.date.issued | 2023-02-13 | - |
dc.identifier.uri | https://doi.org/10.1371/journal.pone.0281580 | - |
dc.identifier.uri | http://ir.mu.ac.ke:8080/jspui/handle/123456789/9080 | - |
dc.description.abstract | Background The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of crypto- coccal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken. Methods In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio. A particular dose was not tested in Stage 2 if there were significant predetermined safety or efficacy concerns.In Stage-2, the 1200mg dose was excluded per protocol because of increased mortality, and participants were randomised to 1600mg, 2000mg FCZ or AMB in a 1:1:1 ratio. Findings One hundred and sixty eight participants were enrolled with 48, 50, and 48 in the AMB, 1600mg and 2000mg cohorts. The Kaplan Meier proportion for mortality (90% CI) at 10 and 24 weeks for AMB was 17% (10, 29) and 24% (15, 37), compared to 20% (12, 32) and 30% (20, 43) for 1600mg, and 33% (23, 46) and 38% (27, 51) for 2000mg/day FCZ. With the exception of a higher incidence of gastrointestinal side effects in the 2000mg cohort, both induction doses of FCZ were safe and well tolerated. There were no life-threatening changes in electrocardiogram QTc which were similar across all doses of FCZ and AMB. The median (IQR) change in log10 cryptoccal colony forming units (CFU) from week 0 to week 2 was -8(-4.1,-1.9) for AMB; -2.5(-4.0, -1.4) for 1600mg FCZ and -8 (-3.2, -1.0) for 2000mg FCZ. The proportion (90% CI) CSF CM negative at 10 weeks was 81%(71,90) for AMB; 56%(45,69) for 1600mg FCZ and 60%(49,73) for 2000mg FCZ. | en_US |
dc.description.sponsorship | UM1 AI068634, UM1 AI068636 and UM1 AI106701; | en_US |
dc.language.iso | en | en_US |
dc.publisher | PLOS ONE | en_US |
dc.subject | Oral Fluconazole | en_US |
dc.subject | Cryptococcal Meningitis | en_US |
dc.title | Higher Dose Oral Fluconazole for the Treatment of AIDS-related Cryptococcal Meningitis (HIFLAC)—report of A5225, a multicentre, phase I/II, two-stage, dose-finding, safety, tolerability and efficacy randomised, amphotericin B-controlled trial of the AIDS Clinical Trials Group | en_US |
dc.type | Article | en_US |
Appears in Collections: | School of Medicine |
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