A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.

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

United States

2018-03-16T19:33:02Z

2018-03-16T19:33:02Z

2018-03-16

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 .).

https://www.ncbi.nlm.nih.gov/pubmed/28614691

1533-4406

https://hdl.handle.net/10161/16185

eng

Massachusetts Medical Society

N Engl J Med

10.1056/NEJMoa1613306

AIDS-Related Opportunistic Infections

Administration, Oral

Adult

Amphotericin B

Antifungal Agents

Creatinine

Deoxycholic Acid

Drug Combinations

Female

Humans

Induction Chemotherapy

Infusions, Intravenous

Itraconazole

Male

Mycoses

Talaromyces

A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.

Journal article

Le, Thuy|0000-0002-3393-6580

https://www.ncbi.nlm.nih.gov/pubmed/28614691

2329

2340

24

Clinical Science Departments

Duke

Medicine

Medicine, Infectious Diseases

School of Medicine

Published

376