LSTM Home > LSTM Research > LSTM Online Archive

Short Course High-dose Liposomal Amphotericin B for HIV-associated Cryptococcal Meningitis: A phase-II Randomized Controlled Trial.

Downloads

Downloads per month over past year

Jarvis, Joseph N, Leeme, Tshepo B, Molefi, Mooketsi, Chofle, Awilly A, Bidwell, Gabriella, Tsholo, Katlego, Tlhako, Nametso, Mawoko, Norah, Patel, Raju K K, Tenforde, Mark W, Muthoga, Charles, Bisson, Gregory P, Kidola, Jeremiah, Changalucha, John, Lawrence, David, Jaffar, Shabbar, Hope, William, Molloy, Si le F and Harrison, Thomas S (2019) 'Short Course High-dose Liposomal Amphotericin B for HIV-associated Cryptococcal Meningitis: A phase-II Randomized Controlled Trial.'. Clinical Infectious Diseases, Vol 68, Issue 3, pp. 393-401.

[img] Text
accepted_short course high-dose.pdf - Accepted Version
Restricted to Repository staff only until 26 June 2019.

Download (873kB)

Abstract

Background
Cryptococcal meningitis (CM) causes 10-20% of HIV-related deaths in Africa. We performed a phase-II non-inferiority trial examining the Early Fungicidal Activity (EFA) of three short-course, high-dose liposomal amphotericin B (L-AmB) regimens for CM in Tanzania and Botswana.
Method
HIV-infected adults with CM were randomized to: (i) L-AmB 10mg/kg day 1 (single dose); (ii) L-AmB 10mg/kg day 1, 5mg/kg day 3 (two doses); (iii) L-AmB 10mg/kg day 1, 5 mg/kg days 3 and 7 (three doses); (iv) standard 14-day L-AmB 3mg/kg/day (control); all given with fluconazole 1200mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid (CSF) cryptococal infection (EFA). Non-inferiority was defined as an upper limit of the two-sided 95% confidence interval (CI) of difference in EFA between intervention and control less than 0.2 log10CFU/ml/day.
Results
80 participants were enrolled. EFA for daily L-AmB was -0.41 (standard deviation 0.11, n=17) log10CFU/mL/day. Difference in mean EFA from control was -0.11 (95%CI -0.29,0.07) log10CFU/mL/day faster with single dose (n=16); -0.05 (95%CI -0.20,0.10) log10CFU/mL/day faster with two doses (n=18); and -0.13 (95%CI -0.35,0.09) log10CFU/mL/day faster with three doses (n=18). EFA in all short-course arms was non-inferior to control at the predefined non-inferiority margin. Overall 10-week mortality was 29% (n=23) with no statistical difference between arms. All arms were well tolerated.
Conclusions
Single dose 10mg/kg L-AmB was well tolerated and led to non-inferior EFA compared to 14 days of 3mg/kg/d L-AmB in HIV-associated CM. Induction based on single 10mg/kg L-AmB dose is being taken forward to a phase-III clinical endpoint trial.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 252 Antifungal agents. Antifungal antibiotics
QW Microbiology and Immunology > Fungi. Pathogenic Fungi. > QW 180 Pathogenic Fungi
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WL Nervous System > WL 200 Meninges. Blood-brain barrier
Faculty: Department: Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI): https://doi.org/10.1093/cid/ciy515
Depositing User: Stacy Murtagh
Date Deposited: 28 Jun 2018 09:06
Last Modified: 24 Jan 2019 09:59
URI: http://archive.lstmed.ac.uk/id/eprint/8861

Statistics

View details

Actions (login required)

Edit Item Edit Item