Single High-dose of Liposomal Amphotericin B in Combination With B/F/TAF for HIV/AIDS-associated Talaromycosis

Summary

This study aims to compare the efficacy and safety of a single high-dose Liposomal Amphotericin B (L-AMB) against conventional Amphotericin B deoxycholate (AmBD) for HIV-associated Talaromycosis.

The investigators hypothesize that L-AMB induction therapy (10 mg/kg) is non-inferior to AmBD (0.5-0.7 mg/kg/d) in efficacy and has an improved safety profile.

The study's primary objective is to provide evidence supporting the guideline recommendation of single high-dose L-AMB for HIV-infected individuals with talaromycosis, while validating L-AMB's efficacy and safety in China.

Study Design: Multi-center, randomized controlled trial comparing single high-dose L-AMB to guideline-recommended AmBD induction therapy for HIV-associated talaromycosis. Participants are HIV-infected adults (≥18 years) with confirmed talaromycosis by microscopy or culture.

Interventions:

1. L-AMB group receives a single intravenous dose of 10 mg/kg L-AMB.
2. Control group receives intravenous AmBD at 0.5-0.7 mg/kg/d for 14 days.
3. Both groups start consolidation therapy with itraconazole 200mg q12h for 10 weeks within 24 hours post-induction.
4. Secondary prophylaxis with itraconazole 200mg qd until CD4+ cell counts exceed 100cells/mm³ for at least 6 months.
5. All start B/F/TAF qd within 7 days post-antifungal therapy.

Primary Objective： This multicenter study compares efficacy/safety of single high-dose L-AMB vs standard AmBD (2-week) induction for HIV-associated talaromycosis, generating evidence to support L-AMB guidelines in Chinese populations.

Secondary Objectives： Evaluate feasibility/safety of initiating B/F/TAF within 7 days post-antifungal therapy, providing evidence for rapid ART guidelines in these patients.

Endpoints:

* Primary: Proportion achieving clinical resolution on day 14.
* Secondary: Overall survival, renal function, anemia, liver function, adverse events grade 3 or higher on day 14; time to clinical resolution and sterile blood cultures; survival, HIV viral suppression, CD4+ T-cell counts, adverse events (including IRIS), ART persistency, and patient-reported outcomes at weeks 4, 12, and 24.

Sample Size: 58 participants per group (116 total), considering a 10% dropout rate.

Conditions

• HIV/AIDS-associated Talaromycosis

Interventions

DRUG

Amphotericin B

After enrollment, participants will be 1:1 randomly assigned into two groups for induction therapy after informed consent: single high-dose L-AmB group (10 mg/kg single intravenous dose of L-AMB) and control group (amphotericin B deoxycholate(AmBD) at 0.5-0.7 mg/kg/d intravenously for 14 days as the standard of care recommended by local guidelines).Thereafter, all participants in both groups will start consolidation therapy within 24 hours of the induction treatment, 200mg itraconazole(or voriconazole) q12h will be given for 10 weeks. After consolidation therapy, all participants will take oral itraconazole 200mg qd as secondary prophylaxis until their CD4+ cell counts are higher than 100cells/mm3 for at least 6 months. For the antiretroviral therapy, all participants will start B/F/TAF qd within 7 days after initiating antifungal therapy

DRUG

AmBisome

After enrollment, participants will be 1:1 randomly assigned into two groups for induction therapy after informed consent: single high-dose L-AmB group (10 mg/kg single intravenous dose of L-AMB) and control group (amphotericin B deoxycholate(AmBD) at 0.5-0.7 mg/kg/d intravenously for 14 days as the standard of care recommended by local guidelines).Thereafter, all participants in both groups will start consolidation therapy within 24 hours of the induction treatment, 200mg itraconazole(or voriconazole) q12h will be given for 10 weeks. After consolidation therapy, all participants will take oral itraconazole 200mg qd as secondary prophylaxis until their CD4+ cell counts are higher than 100cells/mm3 for at least 6 months. For the antiretroviral therapy, all participants will start B/F/TAF qd within 7 days after initiating antifungal therapy.

Sponsors & Collaborators

• Shanghai Public Health Clinical Center

  lead OTHER_GOV

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-05-01

Primary Completion

2026-01-05

Completion

2026-05-01