https://orcid.org/0000-0001-7352-2086
Figures
Abstract
Background
The optimal initial induction treatment for HIV-associated Talaromyces marneffei fungemia (HTMF) remains unclear.
Methods
Three hundred and fifteen patients with HIV-associated Talaromyces marneffei were enrolled in this multicenter retrospective study. The effectiveness of induction regimens with amphotericin B deoxycholate (iAmBd), voriconazole (iVori), and a switch regimen from iVori to AmBd (iVori→AmBd switch) on 180-day all-cause mortality in HTMF patients was assessed.
Results
The prevalence of HTMF was 75.9% (239/315) with a 180-day all-cause mortality of 20.1% (48/239). Among these HTMF patients, 44.4% (106/239) were treated with iAmBd, 41.8% (100/239) with iVori, and 13.8% (33/239) with other regimens. Additionally, 53% (53/100) of patients treated with iVori underwent an iVori→AmBd switch within 7 days. The 180-day cumulative survival rates were 88.7% for patients treated with iAmBd and 77.0% for those treated with iVori; 88.8% for patients who received AmBd within 3 days (iAmBd + 3-day iVori→AmBd switch) and 72.2% for those who continued iVori; 88.2% for patients who received AmBd within 5 days (iAmBd + 5-day iVori→AmBd switch) and 71.0% for those who continued iVori; 88.1% for those who received AmBd within 7 days (iAmBd + 7-day iVori→AmBd switch) and 66.0% for those who continued iVori (all log-rank P < 0.020). The prevalence of adverse drug reactions (ADRs) was 24.5% in the iAmBd group and 9.0% in the iVori group in induction stage (P < 0.001).
Author summary
HIV-associated Talaromyces marneffei fungemia (HTMF) is a severe fungal infection with high mortality rates in people living with HIV (PLWH). Current guidelines recommend amphotericin B deoxycholate (AmBd) as the standard induction therapy. However, its use is often limited due to serious side effects such as kidney damage and electrolyte imbalances. Voriconazole, a newer antifungal drug, has been considered as an alternative due to its broader antifungal activity and fewer side effects. Our study, involving 315 patients across multiple centers, suggests that AmBd is superior to voriconazole in reducing 180-day mortality rates of HTMF. Early initiation of AmBd or early switch from voriconazole to AmBd significantly improved survival, despite the higher incidence of side effects. Our research highlights the need to balance drug efficacy with side effect management in treating severe Talaromyces marneffei infection.
Citation: Ye S, Qin J, Miao X, Lang G, Wang M, Chen G, et al. (2025) Voriconazole is inferior to amphotericin B deoxycholate as the initial induction therapy for HIV-associated Talaromyces marneffei fungemia: A multicenter retrospective study. PLoS Negl Trop Dis 19(4): e0013012. https://doi.org/10.1371/journal.pntd.0013012
Editor: Thuy Le, Duke University School of Medicine, UNITED STATES OF AMERICA
Received: August 13, 2024; Accepted: March 26, 2025; Published: April 8, 2025
Copyright: © 2025 Ye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The data that support the findings of this study are provided in Supporting information file S4 Data.
Funding: The work was supported by National Key Research and Development Program of China (Grant number 2021YFC2301900-2021YFC2301901) to LJX. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Talaromyces marneffei (T. marneffei, TM) is a life-threatening opportunistic fungal infection prevalent among people living with HIV (PLWH) in Southeast Asia and Southern China [1–4]. TM primarily affects the monocyte-macrophage reticuloendothelial system, leading to either disseminated or localized infections [4–6]. HIV-associated Talaromyces marneffei fungemia (HTMF) is one of the most severe forms of this disease, with an in-hospital mortality rate of approximately 20% [7–9]. As a result, identifying the optimal antifungal regimen is crucial for improving patient outcomes.
Current guidelines recommend amphotericin B deoxycholate (AmBd) for 2 weeks as induction therapy, followed by itraconazole (400 mg daily for 10 weeks) as consolidation therapy, and then maintenance therapy with itraconazole (200 mg daily) until CD4 counts exceed 100 cells/mm³ for at least 6 months [10]. However, the use of AmBd is limited by its nephrotoxicity, leukopenia, and electrolyte disturbances [11,12]. Thus, there is a need to explore alternative treatments that can improve clinical outcomes.
Voriconazole (Vori) is a potent and broad-spectrum triazole antifungal agent with efficacy against a wide range of molds, yeasts, and dimorphic fungi [13–15]. Several studies have suggested that Vori is comparable to AmBd as induction therapy for HIV-associated Talaromyces marneffei (HTM) infection [16–18]. However, these studies based on small sample size often fail to distinguish between TM fungemia and localized TM infections. Furthermore, the bias as to who treated with AmBd and who treated with Vori as induction therapy is not fully addressed. Therefore, it is important to investigate whether AmBd and Vori are equally effective as initial induction therapies for HTMF. This multicenter retrospective study aims to compare the efficacy of AmBd versus Vori as initial induction therapies (iAmBd vs. iVori) in HTMF patients.
Methods
Ethics statement
This study protocol was conducted in accordance with the 1975 Declaration of Helsinki and was approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China), Wenzhou Central Hospital (Wenzhou, China), Hangzhou Xixi Hospital (Hangzhou, China), and the Centers for Disease Control (CDC) (No. IIT20210532A). The ethical Committee waived the consent of patient. All data were analyzed anonymously.
Study cohort and patient enrollment
Between January 2013 and August 2024, a total of 315 inpatient cases of HTM from the First Affiliated Hospital of Zhejiang University School of Medicine, Wenzhou Central Hospital, and Xixi Hospital of Hangzhou in China were eligible for inclusion in this study. Inclusion criteria were: a seropositive HIV result, age ≥18 years, and a diagnosis of Talaromycosis confirmed by culture, histopathology, or next-generation sequencing (NGS). Exclusion criteria were: seronegative HIV status, age <18 years, and absence of necessary laboratory and treatment records.
Diagnosis criteria
HTM was diagnosed in PLWH who met at least one of the following criteria: (1)A positive culture result from clinical specimens such as blood, bone marrow, tissue biopsy, sputum, or body fluids; (2) Characteristic yeast cells (2–3 µm in diameter, with oval, round, or sausage-like shapes, and cells that divide by fission) observed in tissue sections by periodic acid-Schiff (PAS) or Wright’s staining; (3) Detection of Talaromyces marneffei DNA by NGS-based methods from blood, bronchoalveolar lavage fluid (BALF), body fluids, or tissue biopsies [10,19,20].
HTMF was defined as a positive peripheral blood culture or positive NGS result from blood in HTM patients exhibiting symptoms such as recurrent fever, rash, severe anemia, splenomegaly, and lymphadenopathy.
Induction antifungal therapy
Antifungal therapy was initiated promptly upon diagnosis of Talaromycosis. The choice of induction regimen followed clinical guidelines and available antifungal agents [10,21], with therapy lasting at least 2 weeks.
iAmBd regimen
Initial induction therapy with AmBd at a dose of 0.7–1.0 mg/kg/day via peripheral intravenous (IV) infusion.
iVori regimen
Initial induction with voriconazole at 6 mg/kg IV every 12 hours for the first 24 hours, followed by 4 mg/kg IV daily.Empirical iVori was administered to patients with suspected Talaromycosis (characterized by fever, localized lymph node enlargement, low or nearly normal white blood cell (WBC) count, elevated C-reactive protein (CRP) levels, signs of fungal infection on pulmonary computed tomography (CT), and increased β-1,3-glucan in plasma) before the diagnosis was confirmed.
iAmBd + iVori regimen
A combination of iAmBd and iVori, using the above dosages, was administered for at least 2 weeks as induction therapy.
iVori→AmBd switch treatment
Treatment was switched from iVori to AmBd (iVori→AmBd switch) among those initially treated with iVori but switch to AmBd during induction treatment under the following conditions: (1) A confirmed diagnosis of HTM in patients previously suspected of Talaromycosis; (2) Intolerable iVori-related adverse drug reactions (ADRs); (3) Uncontrolled fever and worsening inflammatory markers, such as CRP or lactate dehydrogenase (LDH).
Itraconazole regimen
In cases where AmBd or Vori were unavailable, oral itraconazole at 200 mg every 12 hours was used as the induction therapy.
Consolidation therapy and maintenance therapy
After completing at least 14 days of initial induction therapy, all patients were given oral itraconazole at 400 mg daily for 10 weeks as consolidation therapy, followed by 200 mg daily for maintenance therapy (secondary prophylaxis) until their CD4 count remained above 100 cells/μL for more than 6 consecutive months.
Outcome measures
The primary outcome was 180-day all-cause mortality. Secondary outcomes included the incidence of adverse drug reactions (ADRs) during induction treatment. ADRs that occurred after the induction period were not considered treatment-related. ADRs were documented in the electronic medical record system (EMRS) of each hospital and categorized according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [22].
Follow-up and data collection
Patient data, including demographics, laboratory results, clinical signs and symptoms, self-reported adherence, and regimen changes, were collected by hospital staff and local CDC personnel. This data was recorded in the electronic system of the National Free Antiretroviral Treatment Program (NFATP), which automatically generated an electronic database with data verification and cleaning capabilities [23]. Patients were followed from the first day of antifungal treatment until 180 days or death. The follow-up period ended on October 1, 2024. A total of 2.9% (9/315) of participants were lost to follow-up and were treated as right-censored data in the time-to-event analysis.
Statistical analyses
Continuous variables were expressed as mean ± standard deviation for normally distributed data, and as median (interquartile range, IQR) for non-normally distributed data. Categorical variables were presented as frequency (percentage). Comparisons of continuous quantitative variables were made using the Student’s t test, Mann-Whitney U test, χ 2 analysis, or Fisher’s exact test. Data not available were defined as ‘missing data’. All-cause mortality was defined as an ‘event’. Data of patients were censored at the date of the final visit for those alive at the end of the follow-up period, at the date they were last known to be alive for those with unknown vital signs, or the date of participation for those wherein the cause of death was not known to be HTM-related. In the univariate and multivariate Cox regression analyses of risk factors of mortality, continuous variables were log10-transformed (log10) if they were not normally distributed. Covariates with P values < 0.050 in univariate analysis were further analyzed in the multivariate Cox proportional hazards model using the forward (likelihood ratio) method. Patient survival was analyzed by the Kaplan-Meier method, and the Log-rank test was used to assess significance. Tick marks on the KM curves represent censored data points, indicating patients who were lost to follow-up or event-free at the study cutoff. A P value <0.050 was considered statistically significant. Data analyses were performed using SPSS version 25.0 statistical software (IBM, Armonk, NY, USA) and GraphPad version 8.0 (GraphPad Software, La Jolla, California, USA).
Results
Demographic information and clinical characteristics of HTM patients
Among the 315 HTM patients enrolled in this study, 273 (86.7%) were male and 42 (13.3%) were female. The mean age was 38.9 ± 11.6 years, and the mean body mass index (BMI) was 19.9 ± 3.5 kg/m². Of the 315 patients, 239 (75.9%) HTM had fungemia (HTMF), and 76 (24.1%) did not. Among the HTMF patients, 207 (86.6%) were diagnosed via positive blood culture, 26 (10.9%) by positive blood NGS result, and 6 (2.5%) by both positive blood culture and NGS result. Of the 76 non-HTMF patients, diagnoses were made as follows: 33 (43.4%) by positive NGS result from BALF, 4 (5.3%) by NGS from tissue biopsy, 1 (1.3%) by NGS from cerebrospinal fluid, 18 (23.7%) by positive bone marrow culture, 15 (19.7%) by positive histopathology result, 3 (3.9%) by positive sputum culture, and 2 (2.6%) by positive skin culture. The patient selection flowchart was indicated in Fig 1.
HTM, HIV-associated Talaromyces marneffei; HTMF, HIV-associated Talaromyces marneffei fungemia; (+), positive; NGS, next-generation sequencing; BALF, bronchoalveolar lavage fluid; iAmBd + iVori, a combination of iAmBd and iVori; iAmBd, initial induction treatment with amphotericin B deoxycholate; iVori, initial induction treatment with voriconazole; iVori→AmBd switch, switch regimen from initial treatment with voriconazole to AmBd during induction stage.
There were no significant differences between HTMF and non-HTMF patients in terms of sex, age, BMI, comorbidities, or ART initiation. However, significant differences were observed in several laboratory parameters. HTMF patients had significantly lower levels of hemoglobin (g/L; 95.7 ± 19.2 vs. 102.5 ± 19.5, P = 0.008), platelets [× 10⁹/L; 94.0 (43.0-150.0) vs. 143.5 (93.3-217.0), P < 0.001], serum albumin (g/L; 28.2 ± 6.1 vs. 31.7 ± 5.0, P < 0.001), and CD4 count [cells/μL; 9.0 (4.0-20.0) vs. 20.0 (7.0-59.0), P < 0.001]. In contrast, HTMF patients had significantly higher levels of aspartate aminotransferase (AST) [U/L; 87.0 (45.0-155.0) vs. 37.0 (25.0-70.0), P < 0.001], CRP [mg/L; 64.7 (38.4-104.7) vs. 38.4 (9.65-80.0), P < 0.001], and LDH [U/L;470.0 (308.0-746.5) vs. 301.0 (202.3-455.5), P < 0.001] (Table 1).
During the 180-day follow-up, 56 (17.8%) HTM patients died, with a median survival time of 22 (4–39) days. Of these, 48 were HTMF patients and 8 were non-HTMF patients. The median survival time for HTMF patients who died was 16 (4–32) days, while the median survival time for non-HTMF patients who died was 44 (22–90) days (P = 0.041). The 180-day cumulative survival rate was 79.9% in HTMF patients and 89.5% in non-HTMF patients (Log-rank P = 0.049) (Fig 2). The demographic information and clinical characteristics of HTM patients are presented in Table 1.
HTMF, HIV-associated Talaromyces marneffei patient with fungemia; Non-HTMF, HIV-associated Talaromyces marneffei patient without fungemia.
Comparison of 180-day all-cause mortality between iAmBd and iVori regimen in HTMF patients
Among the 239 HTMF patients, 106 (44.3%) received iAmBd, 100 (41.8%) received iVori, 17 (7.1%) received combined iAmBd + iVori, 10 (4.2%) received itraconazole, and 6 (2.5%) abandoned treatment. After excluding patients who received itraconazole, combined iAmBd + iVori, or abandoned treatment due to small sample sizes, the remaining 206 HTMF patients were analyzed (Fig 1). Among these, 35 (17.0%) died during the 180-day follow-up, including 23 (11.2%) who died during hospitalization and 12 (5.8%) who died after discharge. The all-cause mortality was significantly lower in the iAmBd group (11.3%; 12/106) compared to the iVori group (23.0%; 23/100) (P = 0.026). The median survival time for patients who died in the iAmBd group was 42 (29–51) days, compared to 5 (2–28) days in the iVori group (P = 0.002). The 180-day cumulative survival rate was 88.7% for patients treated with iAmBd and 77.0% for those treated with iVori (Log-rank P = 0.018) (Fig 3).
iAmBd, initial induction treatment with amphotericin B deoxycholate; iVori, initial induction treatment with voriconazle.
iVori treatment as an independent risk factor for 180-day all-cause mortality
There were no significant differences between the iVori and iAmBd groups in terms of sex, age, BMI, comorbidities, WBC count, hemoglobin, platelet count, CD4 count, or ART initiation. However, the serum albumin in iAmBd group was higher than that in iVori group [serum albumin (g/L): 28.8 ± 5.7 vs. 26.8 ± 5.7, P = 0.011], while levels of AST and LDH were significantly lower in the iAmBd group compared to the iVori group [AST (U/L): 69.5 (36.5-118.0) vs. 109.5 (51.3-207.5), P = 0.002; LDH (U/L): 397.0 (274.3-542.8) vs. 537.0 (350.3-963.0), P < 0.001] (Table 1).
A Cox proportional hazards model was used to analyze the effects of iAmBd and iVori on the 180-day cumulative survival rate after adjusting for serum albumin, AST, and LDH. In univariate analysis, elevated AST (log10) [HR: 2.646 (1.206-5.808); P = 0.015], creatinine (log10) [HR: 12.778 (2.623-62.237); P = 0.002], and LDH (log10) [HR: 3.725 (1.527-9.083); P = 0.004], as well as iVori treatment [HR: 2.259 (1.124-4.541); P = 0.022], were positively associated with 180-day all-cause mortality. Conversely, higher hemoglobin [HR: 0.977 (0.960-0.995); P = 0.011], platelet count (log10) [HR: 0.193 (0.084-0.443); P < 0.001], and serum albumin [HR: 0.884 (0.832-0.939); P < 0.001] were negatively associated with mortality. In multivariate analysis, elevated serum albumin [HR: 0.896 (0.842-0.953); P = 0.001] was negatively associated with 180-day mortality, while iVori treatment [HR: 2.189 (1.033-4.639); P = 0.041] was positively associated with mortality (S1 Data).
iAmBd and early iVori→AmBd switch increased survival in HTMF patients
Among patients in the iVori group, 28.0% (28/100) underwent the iVori→AmBd switch regimen within 3 days, 10.0% (10/100) within 4–5 days, and 15.0% (15/100) within 6–7 days, and the remaining 47% (47/100) continued with iVori therapy. Totally, 28.0% (28/100) of patients underwent a 3-day iVori→AmBd switch, 38.0% (28 3day switch +10 4–5-day switch)) underwent a 5-day iVori→AmBd switch, and 53.0% (38 5-day switch+15 6–7-day switch) underwent a 7-day iVori→AmBd switch. Of those 53 patients who underwent iVori→AmBd switch, there were 36 underwent switch for confirmed HTM diagnosis from suspected Talaromycosis, 11 for uncontrolled fever, 4 for intolerable iVori-related ADRs, and 2 for increased CRP or LDH level. The indicators for regimen switching in each case are listed in S2 Data.
Overall, 134 patients received AmBd treatment within 3 days (106 iAmBd + 28 3-day iVori→AmBd switch), 144 patients received AmBd within 5 days (106 iAmBd + 38 5-day iVori→AmBd switch), and 159 patients received AmBd within 7 days (106 iAmBd + 53 7-day iVori→AmBd switch). The 180-day cumulative survival rates were 88.8% for patients treated with AmBd within 3 days, compared to 72.2% for those who continued iVori (Log-rank P = 0.001); 88.2% for patients treated with AmBd within 5 days versus 71.0% for those who continued iVori (Log-rank P = 0.001); and 88.1% for patients treated with AmBd within 7 days compared to 66.0% for those who continued iVori (Log-rank P < 0.001) (Fig 4A–C). The 180-day all-cause mortality was 11.3% for those treated with AmBd within 1 days and 23.0% for those treated with Vori without 1-day switch (P = 0.026), 11.2% for those treated with AmBd within 3 day and 27.8% for those treated Vori without 3-day switch (P = 0.003), and 11.8% for those treated with AmBd within 5 days and 29.0% for those treated with Vori without 5-day switch (P = 0.003), 11.9% for those treated with AmBd within 7 days and 34.0% for those treated with Vori without 7-day switch (P < 0.001), respectively (Fig 5).
iAmBd, initial induction treatment with amphotericin B deoxycholate; iVori, initial induction treatment with voriconazle; iVori→AmBd switch, switch regimen from initial treatment with voriconazole to AmBd during induction stage.
AmBd: patients treated with iAmBd and switched AmBd; iVori: patients continued iVori without iVori→AmBd switch.
Adverse drug reactions
The overall incidence of ADRs during induction therapy was 24.5% (26/106) in the iAmBd group and 9.0% (9/100) in the iVori group (P < 0.001). In the iAmBd group, there were 34.6% (9/26) cases with creatinine elevation, 23.1% (6/26) with hypokalemia, 19.2% (5/26) with ALT elevation, 11.5% (3/26) with infusion-related reactions, 7.7% (2/26) with anemia and 3.8% (1/26) with gastrointestinal reactions. Of these, 88.5% (23/26) patients who experienced ADRs switched their treatment from AmBd to Vori, itraconazole, or posaconazole.
In the iVori group, the ADRs included 33.3% (3/9) ALT elevation, 22.2% (2/9) delirium, 11.1% (1/9) hallucination, 11.1% (1/9) had headache, 11.1% (1/9) skin allergy and 11.1% (1/9) visual abnormalities, respectively. Only 9.0% (9/100) of patients in the iVori group switched to iVori→AmBd due to intolerable ADRs.
Furthermore, among those HTMF patients who underwent iVori→AmBd switch, 17.0% (9/53) experienced new AmBd-related ADRs. Detailed information on ADRs is presented in S3 Data.
Disscussion
The optimal initial induction treatment for HTMF remains unclear. Our study provides several important findings: (1) The prevalence of HTMF was 75.9%; (2) the 180-day all-cause mortality rate for HTMF patients was 20.1%, higher than the 10.5% seen in non-HTMF patients; (3) although the overall incidence of ADRs was significantly higher in the iAmBd group compared to the iVori group, the iAmBd regimen was associated with improved survival rates, whereas delayed AmBd treatment significantly increased the mortality in HTMF patients.
HTMF is a life-threatening infection in PLWH [24–26]. In our study, we found that HTMF patients had significantly lower levels of hemoglobin, platelets, serum albumin, and CD4 count, while exhibiting higher levels of AST, CRP, and LDH, compared to non-HTMF patients. These findings suggest that HTMF patients are in a severely deteriorated health condition with a high burden of organ dysfunction, which increases the risk of mortality. Despite prompt antifungal therapy being administered to most HTMF patients, the mortality rate remained high at 20.1%. Therefore, early and potent antifungal regimens are critical to improving clinical outcomes for HTMF patients.
AmBd continues to be the first-line and standard treatment [27]. However, its use is limited by a range of adverse effects, including infusion-related reactions, hypokalemia, anemia, gastrointestinal issues, hepatotoxicity, and nephrotoxicity [28]. This highlights the urgent need for effective and safer alternative antifungal therapies. Voriconazole (Vori), a triazole with broad-spectrum antifungal activity, has shown efficacy against Talaromyces marneffei in both in vitro and in vivo studies [16,17,29]. One study demonstrated that Vori as induction therapy was comparable to AmBd in terms of therapeutic efficacy over a 48-week period in HTM patients [18]. However, another study reported that Vori exhibited a higher minimum inhibitory concentration (MIC) for T. marneffei, leading to delayed clearance of the pathogen from the bloodstream [30]. We hypothesize that the heterogeneity of fungal infections (fungemia versus localized infection) was not adequately addressed in these studies, potentially masking the detrimental impact of fungemia on mortality. In our study, we found that iVori treatment was associated with a 2.2-fold higher risk of mortality compared to iAmBd in HTMF patients after adjusting for confounding factors. Notably, patients who received iAmBd treatment or underwent an early iVori→AmBd switch had higher survival rates compared to those who continued iVori treatment. Therefore, early initiation of AmBd treatment is crucial for improving the prognosis of HTMF patients.
The superiority of iAmBd over iVori in our study may be explained by the following factors: (1) Mechanism of Action: AmBd, a polyene antifungal, exerts a potent fungicidal effect by binding to ergosterol, a component of fungal cell membranes, leading to pore formation and subsequent cell death [31]. In contrast, voriconazole is a fungistatic agent, which may be less effective in cases of high fungal burden or severe infection [13,32]. (2) Pharmacokinetics: T. marneffei primarily infects the monocyte-macrophage reticuloendothelial system, facilitating its spread to organs such as the lungs, liver, and spleen [19]. AmBd can achieve high concentrations and long-lasting activity in these organs [33], making it more effective in treating disseminated infections like HTMF.
Our study has some limitations. First, it is a retrospective cohort study, which may introduce biases. Our data also suggest that physicians may prefer Vori over AmBd as the initial induction treatment for critically ill HTMF patients to avoid the toxicity associated with AmBd. Notably, patients in the iVori group had significantly lower serum albumin levels and higher AST and LDH levels, reflecting a worse health status or greater organ injury. Although our analysis showed that iVori treatment remained an independent risk factor for higher 180-day all-cause mortality after adjusting for hypoalbuminemia, AST, and LDH in the multivariate model, a randomized controlled trial (RCT) is need clarify the efficacy on AmBd vs Vori on HTMF treatment. Second, we only considered AmBd for the treatment of HTMF and did not include liposomal amphotericin B due to its unavailability in China. Third, during the induction treatment period, blood levels of Vori were not monitored in patients receiving iVori therapy. Consequently, it is possible that suboptimal iVori levels contributed to its inferior effectiveness compared to iAmBd.
In conclusion, voriconazole is inferior to AmBd as the initial induction therapy for HTMF patients. Early AmBd administration and early iVori→AmBd switch are significantly associated with improved survival rates, despite the higher incidence of AmBd-related ADRs. A prospective study is urgently needed to compare the efficacy of AmBd versus Vori as induction therapy, with the goal of refining current guidelines for HTM and HTMF treatment.
Supporting information
S1 Data. Risk factors in the multivariate Cox proportional hazards model.
https://doi.org/10.1371/journal.pntd.0013012.s001
(DOCX)
S2 Data. Detailed reasons for switching from iVori to AmBd (iVori→AmBd switch).
https://doi.org/10.1371/journal.pntd.0013012.s002
(DOCX)
S3 Data. ADRs between the iAmBd group and iVori group.
iAmBd, initial induction treatment with amphotericin B deoxycholate; iVori, initial induction treatment with voriconazole; iVori→AmBd switch, switch regimen from initial treatment with voriconazole to AmBd during induction stage; ADRs, adverse drug reactions; →, switch to other drugs; ALT, alanine aminotransferase.
https://doi.org/10.1371/journal.pntd.0013012.s003
(TIF)
S4 Data. The original data for statistic in our study.
https://doi.org/10.1371/journal.pntd.0013012.s004
(XLSX)
Acknowledgments
We thank the staff involved in this study at the First Affiliated Hospital, Zhejiang University School of Medicine. During the preparation of this work, the authors used Chatgpt to improve the language grammar and readability. The authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
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