Browsing by Author "Chau, Nguyen VV"

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    A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.
    (N Engl J Med, 2018-03-16) Le, Thuy; Kinh, Nguyen Van; Cuc, Ngo TK; Tung, Nguyen LN; Lam, Nguyen T; Thuy, Pham TT; Cuong, Do D; Phuc, Pham TH; Vinh, Vu H; Hanh, Doan TH; Tam, Vu Van; Thanh, Nguyen T; Thuy, Tran P; Hang, Nguyen T; Long, Hoang B; Nhan, Ho T; Wertheim, Heiman FL; Merson, Laura; Shikuma, Cecilia; Day, Jeremy N; Chau, Nguyen VV; Farrar, Jeremy; Thwaites, Guy; Wolbers, Marcel; IVAP Investigators
    BACKGROUND: Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking. METHODS: In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile. RESULTS: The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group. CONCLUSIONS: Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).
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    Superiority of a novel Mp1p antigen detection enzyme immunoassay compared to standard BACTEC blood culture in the diagnosis of talaromycosis.
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020-06-21) Thu, Nguyen TM; Chan, Jasper FW; Ly, Vo Trieu; Ngo, Hoa T; Hien, Ha TA; Lan, Nguyen PH; Chau, Nguyen VV; Cai, Jian-Piao; Woo, Patrick CY; Day, Jeremy N; van Doorn, Rogier; Thwaites, Guy; Perfect, John; Yuen, Kwok; Le, Thuy
    BACKGROUND:Talaromycosis is an invasive mycosis endemic in Southeast Asia and causes substantial morbidity and mortality in individuals with advanced HIV disease. Current diagnosis relies on isolating Talaromyces marneffei in cultures, which takes up to 14 days and is detectable only during late-stage infection, leading to high mortality. METHODS:In this retrospective case-control study, we assessed the accuracy of a novel Mp1p antigen-detecting enzyme immunoassay (EIA) in stored plasma samples of 372 patients who had culture-proven talaromycosis from blood or sterile body fluids(reference standard) and of 517 individuals without talaromycosis (338 healthy volunteers; 179 with other infections). All participants were recruited between 2011-2017 in Vietnam. RESULTS:66.1% and 75.4% of cases and controls were male; the median age was 33 and 37, respectively. All cases were HIV-infected; median CD4 count was 10 cells/mm3. At an optical density cut-off of 0.5, the specificity was 98.1% (95% CI: 96.3%-99.0%); the sensitivity was superior to blood culture, 86.3% (95% CI: 82.3%-89.5%) versus 72.8% (95% CI: 68.0%-77.2%), P<0.001, McNemar test. The time-to-diagnosis was 6 hours versus 6.6 ± 3.0 days for blood culture. Paired plasma and urine testing in the same patients (N=269) significantly increased sensitivity compared to testing plasma alone P<0.001, or testing urine alone P=0.02, McNemar tests. CONCLUSIONS:The Mp1p EIA is highly specific and is superior in sensitivity and time-to-diagnosis compared to blood culture for the diagnosis of talaromycosis. Paired plasma and urine testing further increases sensitivity, introducing a new tool for rapid diagnosis, enabling early treatment and potentially reducing mortality.