Guideline

SAHCS Guideline for the prevention, diagnosis and management of cryptococcal disease among persons living with HIV: Update to induction treatment for cryptococcal meningitis

Nelesh P. Govender, Graeme Meintjes, Jonathan Falconer, Kyla Murphy, Jeremy Nel, Helena Rabie, Lisa Frigati, Denasha L. Reddy, Halima Dawood, Ebrahim Variava, Samantha Potgieter, Tom Boyles, Sarah L. Stacey, Petho Mangena, Matamela C. Madua, Camilla Wattrus, Mahomed-Yunus S. Moosa

Received: 05 Nov. 2025; Accepted: 09 Feb. 2026; Published: 18 Mar. 2026

Copyright: © 2026. The Authors. Licensee: AOSIS.
This work is licensed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/).

Induction treatment recommendations

The Southern African HIV Clinicians Society (SAHCS) now recommends a single dose of liposomal amphotericin B (LAmB: 10 mg/kg) with 14 days of flucytosine (100 mg/kg/day in four divided doses) and fluconazole (1200 mg/day) as the first-line induction therapy for cryptococcal meningitis (see Table 1 for dosing). Aligned with the WHO 2022 guideline¹ and the South African Standard Treatment Guidelines (2024),² this is recommended as preferred induction treatment. This recommendation is based on the multicentre AMBisone Therapy Induction OptimisatioN-cryptococcal meningitis (AMBITION-cm) randomised controlled trial (N = 844), which demonstrated that a single high-dose LAmB-containing regimen was non-inferior to a regimen of 7 days of amphotericin B deoxycholate and flucytosine followed by fluconazole (10-week all-cause mortality: 24.8% vs 28.7%), with significantly fewer grade 3–4 adverse events, including fewer cases of anaemia, nephrotoxicity, and thrombophlebitis.³ The high-dose LAmB regimen was well tolerated, preferred by patients and providers, and cost-neutral overall because of reduced monitoring and supportive care needs. Amphotericin B deoxycholate plus flucytosine for 7 days, followed by 7 days of fluconazole, is the recommended alternative regimen if LAmB is unavailable. Amphotericin B deoxycholate plus fluconazole for 14 days is recommended if flucytosine is unavailable.

There are no randomised controlled trials on cryptococcal meningitis in children, but there is nothing to suggest that outcomes with the AMBITION-cm regimen would differ from adults; therefore the same strategy is recommended. Although high-dose fluconazole has not been specifically studied in children or young adolescents, given the low weight of adults in the trial (median 53 kg, interquartile range [IQR]: 47–60), adolescents aged ≥ 13 years and weighing > 40 kg are recommended to receive adult dosing. There is no child-friendly formulation of flucytosine, but 500 mg tablets can be used in children weighing ≥ 17 kg. For children weighing < 17 kg, a single 500 mg tablet can be crushed in 50 mL of distilled water (or Ora-sweet, Ora-plus) to make a 10 mg/mL suspension, with the actual dose to be given calculated per kilogram body weight.

Key practice points for the preferred regimen

The 2019 SAHCS Guideline for the prevention, diagnosis and management of cryptococcal disease among persons living with HIV⁴ should be used as a detailed reference for the administration, and toxicity prevention/management, of amphotericin B deoxycholate, fluconazole, and flucytosine. This update provides information on administration, and toxicity prevention and management for LAmB.

It is important to note that the use of single high-dose LAmB is dependent on the availability of both flucytosine and fluconazole to complete induction treatment. In the absence of flucytosine, it is necessary to revert to a 14-day course of amphotericin B deoxycholate and fluconazole, as detailed in the treatment algorithm (Figure 1). The availability of all three antifungals should be confirmed with the pharmacy prior to prescription.

FIGURE 1: Screening and treatment algorithm for cryptococcal disease.

Administration of LAmB

The total dose of LAmB is calculated as a single dose of 10 mg/kg. This dose does not need to be adjusted in patients with a reduced estimated glomerular filtration rate (Table 1). LAmB powder (50 mg vials) should be stored below 25°C and protected from light during storage (Table 2). Each 50 mg vial should be aseptically reconstituted with 12 mL of sterile water for injection to yield a concentration of 4 mg/mL. The required volume of reconstituted LAmB should then be further diluted in 5% dextrose to a final concentration of 1–2 mg/mL. The reconstituted drug should be injected into 5% dextrose via the provided filters.

LAmB should never be mixed with saline-containing solutions as this will cause precipitation. The prepared infusion should be administered over 2 h via a dedicated intravenous line. If an existing intravenous line is used, it must be flushed with 5% dextrose prior to infusion of LAmB. A test dose is not required, and protection from light during infusion is not necessary. Once prepared, the reconstituted LAmB solution should be used promptly or stored at 2°C – 8°C and infused within 24 h. After completion of the infusion, the line should be flushed with 5% dextrose solution before further use. These recommendations are summarised in Table 2. Simplified dosing and reconstitution guidance is provided in Table 3 (adults) and Table 4 (children and adolescents).

LAmB toxicity prevention and management

LAmB is associated with significantly less nephrotoxicity, and fewer electrolyte disturbances and infusion-related reactions compared to amphotericin B deoxycholate; however, monitoring and supportive care remain important. Pre-hydration is recommended with 1 L of normal saline containing one ampoule of potassium chloride (20 mmol potassium [K+] per 10 mL ampoule) over 2 h prior to infusion to reduce the risk of kidney injury and hypokalaemia. The volume of pre-hydration needed in children and adolescents aged < 13 years, and weighing < 40 kg is 10 mL/kg – 15 mL/kg, with a maximum volume of 1 L over 2–4 h. The child’s weight and nutrition status should be considered when deciding on the infusion rate.

Pre-emptive potassium and magnesium oral supplementation is advised for the first 3 days, unless baseline testing identifies hyperkalaemia (K+ > 5.5 mmol/L). Patients should be given 1200 mg of potassium chloride orally twice daily (equivalent to 16 mmol oral potassium and up to 1500 mg magnesium chloride orally daily if available.

In children, the oral potassium chloride dose should be guided by serum potassium levels, and renal function needs to be considered. If the renal function and the serum potassium level are normal, 1 mEq/kg/day – 2 mEq/kg/day (75 mg/kg/day – 150 mg/kg/day) of potassium divided into 2–3 doses can be considered for the first 3 days and carefully monitored. The dose of magnesium trace element mix for children under 10 kg is 2.5 mL per day, and 5 mL per day if over 10 kg. If magnesium trace element mix is unavailable, the intravenous preparation of magnesium sulphate 50% can be used orally at 0.2 mL/kg as a once daily dose.

Serum potassium, magnesium and creatinine levels should be monitored at baseline, as well as 3 days after treatment. Infusion-related reactions (e.g. fever, chills, rigours) may occur; these are not allergic reactions, and they can be managed by temporarily slowing the infusion rate, administering paracetamol, or using antihistamines if needed. Phlebitis is rare, but can be minimised by using a dedicated intravenous line, flushing the line with 5% dextrose after the infusion, and removing or re-siting the line if there is redness or discomfort.

Acknowledgements

The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article. The authors, Graeme Meintjes and Camilla Wattrus, serve as editorial board members of this journal. The authors have no other competing interests to declare.

Nelesh P. Govender: Conceptualisation, writing – original draft, writing – review & editing, supervision. Graeme Meintjes: Conceptualisation, writing – original draft, writing – review & editing. Jonathan Falconer: Writing – original draft, writing – review & editing. Kyla Murphy: Writing – original draft, writing – review & editing. Jeremy S. Nel: Writing – original draft, writing – review & editing. Helena Rabie: Writing – review & editing. Lisa Frigati: Writing – original draft, writing – review & editing. Denasha L. Reddy: Writing – review & editing. Halima Dawood: Writing – review & editing. Ebrahim Variava: Writing – review & editing. Samantha Potgieter: Writing – review & editing. Tom Boyles: Writing – review & editing. Sarah L. Stacey: Writing – review & editing. Petho Mangena: Writing – review & editing. Matamela C. Madua: Writing – review & editing. Camilla Wattrus: Writing – review & editing and project management. Mahomed-Yunus S. Moosa: Writing – review & editing. All authors reviewed the article, contributed to the discussion recommendations approved the final version for submission and publication, and take responsibility for the integrity of its findings.

This guideline does not contain any studies involving human participants performed by any of the authors.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data sharing is not applicable to this article as no new data were created or analysed.

The views and opinions expressed in this article are those of the authors and are the product of professional research. They do not necessarily reflect the official policy or position of any affiliated institution, funder, agency, or that of the publisher. To the fullest extent permitted by law, the Southern African HIV Clinicians Society (SAHCS) and the authors of this document cannot be held liable for any aspect of healthcare administered with the aid of this information or any other use of this information, including any use which is not in accordance with any guidelines or (mis-)use. Specific recommendations provided here are intended only as a guide to clinical management, based on expert consensus and best current evidence at the date of first publication. Management decisions for patients should be made by their responsible clinicians, with due consideration for individual circumstances and various contexts. The information contained in this document should not be considered a substitute for such professional judgment. The most current version of this document should always be consulted.

References