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.

Timeline

Start

2025-05-01

Primary completion

2026-01-05

Completion

2026-05-01

Publications

• Background Le T, Kinh NV, Cuc NTK, Tung NLN, Lam NT, Thuy PTT, Cuong DD, Phuc PTH, Vinh VH, Hanh DTH, Tam VV, Thanh NT, Thuy TP, Hang NT, Long HB, Nhan HT, Wertheim HFL, Merson L, Shikuma C, Day JN, Chau NVV, Farrar J, Thwaites G, Wolbers M; IVAP Investigators. A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis. N Engl J Med. 2017 Jun 15;376(24):2329-2340. doi: 10.1056/NEJMoa1613306.
• Background Adler-Moore J, Lewis RE, Bruggemann RJM, Rijnders BJA, Groll AH, Walsh TJ. Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B. Clin Infect Dis. 2019 May 2;68(Suppl 4):S244-S259. doi: 10.1093/cid/ciz064.
• Background Sundar S, Chakravarty J, Agarwal D, Rai M, Murray HW. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med. 2010 Feb 11;362(6):504-12. doi: 10.1056/NEJMoa0903627.
• Background Jarvis JN, Lawrence DS, Meya DB, Kagimu E, Kasibante J, Mpoza E, Rutakingirwa MK, Ssebambulidde K, Tugume L, Rhein J, Boulware DR, Mwandumba HC, Moyo M, Mzinganjira H, Kanyama C, Hosseinipour MC, Chawinga C, Meintjes G, Schutz C, Comins K, Singh A, Muzoora C, Jjunju S, Nuwagira E, Mosepele M, Leeme T, Siamisang K, Ndhlovu CE, Hlupeni A, Mutata C, van Widenfelt E, Chen T, Wang D, Hope W, Boyer-Chammard T, Loyse A, Molloy SF, Youssouf N, Lortholary O, Lalloo DG, Jaffar S, Harrison TS; Ambition Study Group. Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. N Engl J Med. 2022 Mar 24;386(12):1109-1120. doi: 10.1056/NEJMoa2111904.
• Background Acquired Immunodeficiency Syndrome Professional Group, Society of Infectious Diseases, Chinese Medical Association; Chinese Center for Disease Control and Prevention. Chinese guidelines for the diagnosis and treatment of human immunodeficiency virus infection/acquired immunodeficiency syndrome (2024 edition). Chin Med J (Engl). 2024 Nov 20;137(22):2654-2680. doi: 10.1097/CM9.0000000000003383. Epub 2024 Nov 18.
• Background Pasqualotto AC, Lana DD, Godoy CSM, Leitao TDMJS, Bay MB, Damasceno LS, Soares RBA, Kist R, Silva LR, Wiltgen D, Melo M, Guimaraes TF, Guimaraes MR, Vechi HT, de Mesquita JRL, Monteiro GRG, Adenis A, Bahr NC, Spec A, Boulware DR, Israelski D, Chiller T, Falci DR. Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial. Clin Infect Dis. 2023 Oct 13;77(8):1126-1132. doi: 10.1093/cid/ciad313.
• Background Bicanic T, Bottomley C, Loyse A, Brouwer AE, Muzoora C, Taseera K, Jackson A, Phulusa J, Hosseinipour MC, van der Horst C, Limmathurotsakul D, White NJ, Wilson D, Wood R, Meintjes G, Harrison TS, Jarvis JN. Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis. Antimicrob Agents Chemother. 2015 Dec;59(12):7224-31. doi: 10.1128/AAC.01698-15. Epub 2015 Sep 8.
• Background Ullmann AJ. Nephrotoxicity in the setting of invasive fungal diseases. Mycoses. 2008;51 Suppl 1:25-30. doi: 10.1111/j.1439-0507.2008.01525.x.
• Background Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-andadolescent-opportunistic-infection. Accessed 25/6/2024
• Background Wang F, Han R, Chen S. An Overlooked and Underrated Endemic Mycosis-Talaromycosis and the Pathogenic Fungus Talaromyces marneffei. Clin Microbiol Rev. 2023 Mar 23;36(1):e0005122. doi: 10.1128/cmr.00051-22. Epub 2023 Jan 17.
• Background Guo P, Li L, Tang X. Advances in diagnosis and treatment of talaromycosis in patients with AIDS. Chin Med J (Engl). 2022 Nov 20;135(22):2687-2689. doi: 10.1097/CM9.0000000000002506. No abstract available.
• Yan X, Meng X, Song W, Liu L, Chen J, Zhang R, Shen Y. Single high-dose liposomal amphotericin B plus B/F/TAF for AIDS-associated talaromycosis in China: a multicentre randomised controlled trial protocol. BMJ Open. 2025 Nov 19;15(11):e105648. doi: 10.1136/bmjopen-2025-105648.

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