<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1d1 20130915//EN" "http://jats.nlm.nih.gov/publishing/1.1d1/JATS-journalpublishing1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" article-type="other" xml:lang="en">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">HIVMED</journal-id>
<journal-title-group>
<journal-title>Southern African Journal of HIV Medicine</journal-title>
</journal-title-group>
<issn pub-type="ppub">1608-9693</issn>
<issn pub-type="epub">2078-6751</issn>
<publisher>
<publisher-name>AOSIS</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">HIVMED-27-1789</article-id>
<article-id pub-id-type="doi">10.4102/sajhivmed.v27i1.1789</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Guideline</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>SAHCS Guideline for the prevention, diagnosis and management of cryptococcal disease among persons living with HIV: Update to induction treatment for cryptococcal meningitis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7869-9462</contrib-id>
<name>
<surname>Govender</surname>
<given-names>Nelesh P.</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="aff" rid="AF0002">2</xref>
<xref ref-type="aff" rid="AF0003">3</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1196-4414</contrib-id>
<name>
<surname>Meintjes</surname>
<given-names>Graeme</given-names>
</name>
<xref ref-type="aff" rid="AF0004">4</xref>
<xref ref-type="aff" rid="AF0005">5</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8297-8138</contrib-id>
<name>
<surname>Falconer</surname>
<given-names>Jonathan</given-names>
</name>
<xref ref-type="aff" rid="AF0006">6</xref>
<xref ref-type="aff" rid="AF0007">7</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3338-5862</contrib-id>
<name>
<surname>Murphy</surname>
<given-names>Kyla</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="aff" rid="AF0008">8</xref>
<xref ref-type="aff" rid="AF0009">9</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4115-894X</contrib-id>
<name>
<surname>Nel</surname>
<given-names>Jeremy</given-names>
</name>
<xref ref-type="aff" rid="AF0006">6</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6336-2963</contrib-id>
<name>
<surname>Rabie</surname>
<given-names>Helena</given-names>
</name>
<xref ref-type="aff" rid="AF0010">10</xref>
<xref ref-type="aff" rid="AF0011">11</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4097-3128</contrib-id>
<name>
<surname>Frigati</surname>
<given-names>Lisa</given-names>
</name>
<xref ref-type="aff" rid="AF0010">10</xref>
<xref ref-type="aff" rid="AF0011">11</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1199-021X</contrib-id>
<name>
<surname>Reddy</surname>
<given-names>Denasha L.</given-names>
</name>
<xref ref-type="aff" rid="AF0006">6</xref>
<xref ref-type="aff" rid="AF0012">12</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8180-6791</contrib-id>
<name>
<surname>Dawood</surname>
<given-names>Halima</given-names>
</name>
<xref ref-type="aff" rid="AF0013">13</xref>
<xref ref-type="aff" rid="AF0014">14</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2888-789X</contrib-id>
<name>
<surname>Variava</surname>
<given-names>Ebrahim</given-names>
</name>
<xref ref-type="aff" rid="AF0015">15</xref>
<xref ref-type="aff" rid="AF0016">16</xref>
<xref ref-type="aff" rid="AF0017">17</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7408-9787</contrib-id>
<name>
<surname>Potgieter</surname>
<given-names>Samantha</given-names>
</name>
<xref ref-type="aff" rid="AF0018">18</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5676-8081</contrib-id>
<name>
<surname>Boyles</surname>
<given-names>Tom</given-names>
</name>
<xref ref-type="aff" rid="AF0019">19</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0042-8288</contrib-id>
<name>
<surname>Stacey</surname>
<given-names>Sarah L.</given-names>
</name>
<xref ref-type="aff" rid="AF0006">6</xref>
<xref ref-type="aff" rid="AF0020">20</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4355-6119</contrib-id>
<name>
<surname>Mangena</surname>
<given-names>Petho</given-names>
</name>
<xref ref-type="aff" rid="AF0021">21</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-5942-3590</contrib-id>
<name>
<surname>Madua</surname>
<given-names>Matamela C.</given-names>
</name>
<xref ref-type="aff" rid="AF0022">22</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2075-7903</contrib-id>
<name>
<surname>Wattrus</surname>
<given-names>Camilla</given-names>
</name>
<xref ref-type="aff" rid="AF0023">23</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6191-4023</contrib-id>
<name>
<surname>Moosa</surname>
<given-names>Mahomed-Yunus S.</given-names>
</name>
<xref ref-type="aff" rid="AF0024">24</xref>
</contrib>
<aff id="AF0001"><label>1</label>Wits Mycology Division, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa</aff>
<aff id="AF0002"><label>2</label>Institute for Infection and Immunity, City St. George&#x2019;s University of London, London, United Kingdom</aff>
<aff id="AF0003"><label>3</label>MRC Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom</aff>
<aff id="AF0004"><label>4</label>Blizard Institute, Queen Mary University of London, London, United Kingdom</aff>
<aff id="AF0005"><label>5</label>Department of Medicine and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa</aff>
<aff id="AF0006"><label>6</label>Division of Infectious Diseases, Department of Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa</aff>
<aff id="AF0007"><label>7</label>Division of Clinical Microbiology, Department of Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa</aff>
<aff id="AF0008"><label>8</label>Department of Medicine, University of Cape Town, Cape Town, South Africa</aff>
<aff id="AF0009"><label>9</label>Neuroscience Institute, University of Cape Town, Cape Town, South Africa</aff>
<aff id="AF0010"><label>10</label>Department of Paediatrics, Stellenbosch University, Stellenbosch, South Africa</aff>
<aff id="AF0011"><label>11</label>Department of Paediatrics, Tygerberg Hospital, Cape Town, South Africa</aff>
<aff id="AF0012"><label>12</label>Vaccines and Infectious Diseases Analytics Research Unit (Wits-Vida), University of the Witwatersrand, Johannesburg, South Africa</aff>
<aff id="AF0013"><label>13</label>Infectious Disease Unit, Greys Hospital, Pietermaritzburg, South Africa</aff>
<aff id="AF0014"><label>14</label>Centre for the AIDS Programme of Research in South Africa, (CAPRISA), University of KwaZulu-Natal, Durban, South Africa</aff>
<aff id="AF0015"><label>15</label>Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa</aff>
<aff id="AF0016"><label>16</label>Klerksdorp Tshepong Hospital Complex, Klerksdorp, South Africa</aff>
<aff id="AF0017"><label>17</label>Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa</aff>
<aff id="AF0018"><label>18</label>Department of Internal Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa</aff>
<aff id="AF0019"><label>19</label>Clinical HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa</aff>
<aff id="AF0020"><label>20</label>Department of Medicine, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa</aff>
<aff id="AF0021"><label>21</label>Department of Medicine, Polokwane Hospital, Polokwane, South Africa</aff>
<aff id="AF0022"><label>22</label>Department of Cardiology, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa</aff>
<aff id="AF0023"><label>23</label>Southern African HIV Clinicians Society (SAHCS), Johannesburg, South Africa</aff>
<aff id="AF0024"><label>24</label>Department of Infectious Disease, Division of Internal Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa</aff>
</contrib-group>
<author-notes>
<corresp id="cor1"><bold>Corresponding author:</bold> Nelesh Govender, <email xlink:href="nelesh.govender@wits.ac.za">nelesh.govender@wits.ac.za</email></corresp>
</author-notes>
<pub-date pub-type="epub"><day>18</day><month>03</month><year>2026</year></pub-date>
<pub-date pub-type="collection"><year>2026</year></pub-date>
<volume>27</volume>
<issue>1</issue>
<elocation-id>1789</elocation-id>
<history>
<date date-type="received"><day>05</day><month>11</month><year>2025</year></date>
<date date-type="accepted"><day>09</day><month>02</month><year>2026</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2026. The Authors</copyright-statement>
<copyright-year>2026</copyright-year>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
<license-p>Licensee: AOSIS. This work is licensed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.</license-p>
</license>
</permissions>
<funding-group>
<funding-statement><bold>Funding information</bold> This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.</funding-statement>
</funding-group>
</article-meta>
</front>
<body>
<sec id="s0001">
<title>Induction treatment recommendations</title>
<p>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 <xref ref-type="table" rid="T0001">Table 1</xref> for dosing). Aligned with the WHO 2022 guideline<sup><xref ref-type="bibr" rid="CIT0001">1</xref></sup> and the South African Standard Treatment Guidelines (2024),<sup><xref ref-type="bibr" rid="CIT0002">2</xref></sup> 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 (<italic>N</italic> = 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&#x0025; vs 28.7&#x0025;), with significantly fewer grade 3&#x2013;4 adverse events, including fewer cases of anaemia, nephrotoxicity, and thrombophlebitis.<sup><xref ref-type="bibr" rid="CIT0003">3</xref></sup> 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.</p>
<table-wrap id="T0001">
<label>TABLE 1</label>
<caption><p>Induction therapy doses of flucytosine, fluconazole, and amphotericin B, adjusted according to estimated glomerular filtration rates.</p></caption>
<table frame="hsides" rules="groups">
<thead >
<tr>
<th valign="top" align="left">Antifungal agent</th>
<th valign="top" align="left">eGFR &#x003E; 50 mL/min</th>
<th valign="top" align="left">eGFR 10&#x2013;50 mL/min</th>
<th valign="top" align="left">eGFR &#x003C; 10 mL/min</th>
<th valign="top" align="left">Haemodialysis</th>
</tr>
</thead>
<tbody >
<tr>
<td align="left"><bold>Liposomal amphotericin B</bold><xref ref-type="table-fn" rid="TFN0001">&#x2020;</xref></td>
<td align="left">10 mg/kg single dose</td>
<td align="left">10 mg/kg single dose</td>
<td align="left">10 mg/kg single dose</td>
<td align="left">10 mg/kg single dose (not dialysed)</td>
</tr>
<tr>
<td align="left"><bold>Amphotericin B deoxycholate</bold><xref ref-type="table-fn" rid="TFN0001">&#x2020;</xref></td>
<td align="left">1 mg/kg</td>
<td align="left">1 mg/kg on alternate days<xref ref-type="table-fn" rid="TFN0002">&#x2021;</xref></td>
<td align="left">1 mg/kg on alternate days<xref ref-type="table-fn" rid="TFN0002">&#x2021;</xref></td>
<td align="left">1 mg/kg (can administer during dialysis)</td>
</tr>
<tr>
<td align="left"><bold>Fluconazole</bold><break/>(Adults and adolescents &#x003E; 13 years and &#x003E; 40 kg)</td>
<td align="left">1200 mg daily</td>
<td align="left">600 mg daily</td>
<td align="left">600 mg daily</td>
<td align="left">600 mg daily; dose after dialysis</td>
</tr>
<tr>
<td align="left"><bold>Fluconazole</bold><break/>(Children and adolescents &#x003C; 13 years and &#x003C; 40 kg)<xref ref-type="table-fn" rid="TFN0001">&#x2020;</xref></td>
<td align="left">Stat dose of 25 mg/kg then 12 mg/kg/dose; max dose800 mg</td>
<td align="left">6 mg/kg/dose; max dose200 mg</td>
<td align="left">3 mg/kg/dose &#x2013; 6 mg/kg/dose; max dose 200 mg</td>
<td align="left">3 mg/kg/dose &#x2013; 6 mg/kg/dose; max dose 00 mg</td>
</tr>
<tr>
<td align="left"><bold>Flucytosine?</bold><break/>(see <xref ref-type="table" rid="T0004">Table 4</xref> for specific dosing guidance)</td>
<td align="left">25 mg/kg 6 hourly</td>
<td align="left">25 mg/kg 12 hourly</td>
<td align="left">25 mg/kg daily</td>
<td align="left">25 mg/kg daily; dose after dialysis</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p><italic>Source</italic>: Adapted from Gilbert DN, Eliopoulos GM, Chambers HF, et al., editors. Sanford guide to antimicrobial therapy 2024. 54th ed. Sperryville, VA: Antimicrobial Therapy, Inc.; 2024.<sup><xref ref-type="bibr" rid="CIT0005">5</xref></sup></p></fn>
<fn><p>eGFR, estimated glomerular filtration rate.</p></fn>
<fn id="TFN0001"><label>&#x2021;</label><p>, Children with renal dysfunction should be discussed with an experienced clinician.</p></fn>
<fn id="TFN0002"><label>&#x2021;</label><p>, Amphotericin B deoxycholate is nephrotoxic but not renally excreted, so increased spacing is to reduce nephrotoxicity rather than to adjust for reduced renal clearance. If amphotericin B deoxycholate was intended to be given for 2 weeks, for example, alternate-day spacing over the 2-week period would mean that only 7 doses would be given in total.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>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&#x2013;60), adolescents aged &#x2265; 13 years and weighing &#x003E; 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 &#x2265; 17 kg. For children weighing &#x003C; 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.</p>
</sec>
<sec id="s0002">
<title>Key practice points for the preferred regimen</title>
<p>The 2019 SAHCS Guideline for the prevention, diagnosis and management of cryptococcal disease among persons living with HIV<sup><xref ref-type="bibr" rid="CIT0004">4</xref></sup> 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.</p>
<boxed-text>
<caption><p>Key practice point</p></caption>
<p>Liposomal amphotericin B is significantly different from amphotericin B deoxycholate. The daily doses are different, as are the reconstitution/ administration requirements and toxicity profiles. This should be highlighted to all clinicians, nurses, and pharmacists involved in its use.</p>
</boxed-text>
<p>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 (<xref ref-type="fig" rid="F0001">Figure 1</xref>). The availability of all three antifungals should be confirmed with the pharmacy prior to prescription.</p>
<fig id="F0001">
<label>FIGURE 1</label>
<caption><p>Screening and treatment algorithm for cryptococcal disease.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="HIVMED-27-1789-g001.tif"/>
</fig>
<sec id="s20003">
<title>Administration of LAmB</title>
<p>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 (<xref ref-type="table" rid="T0001">Table 1</xref>). LAmB powder (50 mg vials) should be stored below 25&#x00B0;C and protected from light during storage (<xref ref-type="table" rid="T0002">Table 2</xref>). 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&#x0025; dextrose to a final concentration of 1&#x2013;2 mg/mL. The reconstituted drug should be injected into 5&#x0025; dextrose via the provided filters.</p>
<table-wrap id="T0002">
<label>TABLE 2</label>
<caption><p>Summary of administration and toxicity prevention and/or monitoring and/or management for amphotericin B (the full table for other induction agents are detailed in SAHCS 2019 guidelines).<sup><xref ref-type="bibr" rid="CIT0004">4</xref></sup></p></caption>
<table frame="hsides" rules="groups">
<thead >
<tr>
<th valign="top" align="left">Scenario<hr/></th>
<th valign="top" align="left">Sub-recommendations<hr/></th>
</tr>
<tr>
<th valign="top" colspan="2" align="left">Key practice point: LAmB and amphotericin B deoxycholate are very different formulations and must not be confused.</th>
</tr>
</thead>
<tbody >
<tr>
<td align="left">Administration of LAmB</td>
<td align="left"><list list-type="bullet">
<list-item><p>Reconstitute each vial with 12 mL of sterile water to obtain a concentration of 4 mg/mL (assumes a 0.5 mL displacement volume for the powder). Shake the vial for 30 s to ensure the powder has dissolved.</p></list-item>
</list><bold>For adults and adolecents &#x003E; 13 years and &#x003E; 40 kg:</bold>
<list list-type="bullet">
<list-item><p>LAmB should be reconstituted in sterile water; inject the calculated volume of reconstituted antifungal in water through the provided filters into 1 L of 5&#x0025; dextrose and infuse over 2 h. The equivalent amount of 5&#x0025; dextrose fluid will need to be removed prior to addition of the reconstituted antifungal volume. Administer within 24 h of reconstitution and ensure it is stored at 2&#x00B0;C &#x2013; 8&#x00B0;C. The reconsituted bag does not need to be protected from light. Flush line with 5&#x0025; dextrose before and after infusion.</p></list-item>
<list-item><p>LAmB can be administered via a peripheral intravenous (IV) line if the concentration is &#x003C; 2 mg/mL.</p></list-item>
<list-item><p>A test dose is unnecessary.</p></list-item>
</list><bold>For children and adolescents &#x003C; 13 years and &#x003C; 40 kg:</bold>
<list list-type="bullet">
<list-item><p>See <xref ref-type="table" rid="T0004">Table 4</xref> for dilution.</p></list-item>
<list-item><p>Note: Follow <xref ref-type="table" rid="T0004">Table 4</xref> if 200 mL 5&#x0025; dextrose is available. Follow Table 5 (Appendix 1) if 200 mL 5&#x0025; dextrose is unavailable, and instead use 1 L 5&#x0025; dextrose and 150 mL buretrol.</p></list-item>
</list></td>
</tr>
<tr>
<td align="left">Administration of amphotericin B deoxycholate<break/>(adults and adolescents &#x003E; 40 kg)</td>
<td align="left"><list list-type="bullet">
<list-item><p>Amphotericin B deoxycholate powder should be reconstituted in sterile water; inject the calculated volume of reconstituted antifungal in water into 1 L of 5&#x0025; dextrose water and administer within 24 h.</p></list-item>
<list-item><p>Amphotericin B deoxycholate can be administered via a peripheral IV line if the solution contains &#x2264; 0.1 mg of amphotericin B deoxycholate per 1 mL of 5&#x0025; dextrose water.</p></list-item>
<list-item><p>A test dose is unnecessary.</p></list-item>
<list-item><p>The solution should be infused over at least 4 h.</p></list-item>
</list></td>
</tr>
<tr>
<td align="left">Administration of amphotericin B deoxycholate<break/>(children and adolescents &#x003C; 40 kg)</td>
<td align="left"><list list-type="bullet">
<list-item><p>Reconstitute each 50 mg vial with 10 mL sterile water to make a 5 mg/mL solution.</p></list-item>
<list-item><p>Calculate the patient requirement in mL of reconstituted amphotericin B deoxycholate, that is, mL of reconstituted deoxycholate required = patient dose/5</p></list-item>
<list-item><p>Dilute with 5&#x0025; dextrose; infusion should be over at least 4 h.</p></list-item>
<list-item><p>Flush line with 5&#x0025; dextrose before and after infusion.</p></list-item>
</list></td>
</tr>
<tr>
<td align="left">Administration of flucytosine<xref ref-type="table-fn" rid="TFN0003">&#x2021;</xref></td>
<td align="left"><list list-type="bullet">
<list-item><p>Flucytosine comes in 500 mg tablets (or capsules, depending on the manufacturer). These should be administered by weight-based dosing. Suggested dosing regimens are shown in <xref ref-type="table" rid="T0003">Table 3</xref> and <xref ref-type="table" rid="T0004">Table 4</xref>.</p></list-item>
<list-item><p>If a patient is unable to swallow, tablets can be crushed and administered via a nasogastric tube.</p></list-item>
<list-item><p>In a child weighing &#x003C; 17 kg, a single 500 mg tablet can be mixed with 50 mL of Ora-sweet, Ora-plus, or distilled water, and delivered as a 10 mg/mL solution, as per the dosing schedule in <xref ref-type="table" rid="T0004">Table 4</xref>.</p></list-item>
</list></td>
</tr>
<tr>
<td align="left">Prevention of amphotericin B-related toxicities (both formulations)</td>
<td align="left"><list list-type="bullet">
<list-item><p>Adults should be pre-hydrated with 1 L of normal saline containing one ampoule of potassium chloride (20 mmol) infused over 2 h before the amphotericin B infusion<xref ref-type="table-fn" rid="TFN0004">&#x00A7;</xref></p></list-item>
<list-item><p>Twice daily oral potassium and daily oral magnesium supplementation should be administered to adults until 2 days after the final dose of amphotericin B.</p></list-item>
<list-item><p>To minimise the risk of phlebitis, lines should be flushed with 5&#x0025; dextrose immediately after the amphotericin B infusion is complete and the infusion bag should not be left attached to the intravenous administration set after the infusion is complete.</p></list-item>
</list></td>
</tr>
<tr>
<td align="left">Monitoring of patients receiving liposomal amphotericin B and flucytosine</td>
<td align="left"><list list-type="bullet">
<list-item><p><bold>Days 0 and 3:</bold> creatinine and potassium (and magnesium, if available).</p></list-item>
<list-item><p><bold>Days 0 and 7:</bold> full blood count (with a differential count if available).</p></list-item>
<list-item><p><bold>Day 3:</bold> full blood count and differential count can be considered when flucytosine is used, especially if baseline abnormalities exist. Flucytosine may cause bone marrow suppression but this is uncommon with a short duration of use, the current suggested dosing schedule and in the absence of renal impairment.</p></list-item>
<list-item><p>Fluid input and output monitoring.</p></list-item>
</list></td>
</tr>
<tr>
<td align="left">Management of amphotericin B-related toxicities (both formulations)</td>
<td align="left"><list list-type="bullet">
<list-item><p><bold>Infusion reactions:</bold> Rigours and febrile reactions are common.</p></list-item>
<list-item><p>They can be treated by slowing the rate of infusion and administering paracetamol 1 g 30 min before the infusion (if severe, hydrocortisone 25 mg IV can be given before subsequent infusions).</p></list-item>
<list-item><p><bold>Renal impairment:</bold> As LAmB is administered as a single dose, no subsequent dose adjustment is necessary. Otherwise close monitoring and supportive treatment is normally sufficient.</p></list-item>
<list-item><p>For recommendations regarding amphotericin B deoxycholate, refer to recommendation 4 (renal impairment section) of the 2019 guidelines.<sup><xref ref-type="bibr" rid="CIT0004">4</xref></sup></p></list-item>
<list-item><p><bold>Anaemia:</bold> Transfuse according to local guidelines.</p></list-item>
<list-item><p><bold>Potassium and magnesium impairment:</bold> For significant hypokalaemia (serum K+ &#x003C; 3.3 mmol/L), additional intravenous replacement is required: up to two ampoules of potassium chloride (20 mmol K+ per 10 mL ampoule) in 1 L of normal saline 8 hourly. Among those who develop hypokalaemia, serum potassium should be monitored daily until it is resolved. If hypokalaemia remains uncorrected, serum magnesium should be checked (if this test is available) and/or oral magnesium supplementation should be doubled. Intravenous magnesium sulphate may be considered for persistent hypokalaemia and hypomagnesaemia.</p></list-item>
</list></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p>LAmB, liposomal amphotericin B.</p></fn>
<fn id="TFN0003"><label>&#x2021;</label><p>, For adolescents and children, doses should be calculated by body weight.</p></fn>
<fn id="TFN0004"><label>&#x00A7;</label><p>, For children and adolescents, normal saline, with one ampoule of potassium chloride (20 mmol) added per 1 L of fluid, should be infused at 10 mL/kg &#x2013; 15 mL/kg over 2&#x2013;4 h (not more than 1 L) prior to amphotericin B administration. If saline is unavailable, then other parenteral rehydration solutions, for example Ringer&#x2019;s lactate, that already contain potassium can be used.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>LAmB should <bold><italic>never</italic></bold> 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&#x0025; 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&#x00B0;C &#x2013; 8&#x00B0;C and infused within 24 h. After completion of the infusion, the line should be flushed with 5&#x0025; dextrose solution before further use. These recommendations are summarised in <xref ref-type="table" rid="T0002">Table 2</xref>. Simplified dosing and reconstitution guidance is provided in <xref ref-type="table" rid="T0003">Table 3</xref> (adults) and <xref ref-type="table" rid="T0004">Table 4</xref> (children and adolescents).</p>
<table-wrap id="T0003">
<label>TABLE 3</label>
<caption><p>Simplified dosing and reconstitution guidance for LAmB and flucytosine.</p></caption>
<table frame="hsides" rules="groups">
<thead >
<tr>
<th valign="top" align="left">Liposomal amphotericin B (10 mg/kg) IV (in 5&#x0025; dextrose)</th>
<th valign="top" align="center">Patient weight (kg)</th>
<th valign="top" align="center">Dose (mg)</th>
<th valign="top" align="center">Number of 50 mg vials</th>
<th valign="top" align="center">Volume (to remove from IV bag before adding LAmB)</th>
<th valign="top" align="center">Flucytosine (100 mg/kg/day in four divided doses) Oral</th>
<th valign="top" align="center">Patient weight (kg)</th>
<th valign="top" align="center">Total daily dose (mg)</th>
<th valign="top" align="center">Number of 500 mg pills/day</th>
<th valign="top" align="center">Suggested dosing schedule</th>
</tr>
</thead>
<tbody >
<tr>
<td align="left"></td>
<td align="center">41&#x2013;45</td>
<td align="center">450</td>
<td align="center">9</td>
<td align="center">112.5 mL</td>
<td align="left"></td>
<td align="center">40&#x2013;44</td>
<td align="center">4000</td>
<td align="center">8</td>
<td align="center">2&#x2013;2&#x2013;2&#x2013;2</td>
</tr>
<tr>
<td align="left"></td>
<td align="center">46&#x2013;50</td>
<td align="center">500</td>
<td align="center">10</td>
<td align="center">125 mL</td>
<td align="left"></td>
<td align="center">45&#x2013;49</td>
<td align="center">4500</td>
<td align="center">9</td>
<td align="center">3&#x2013;2&#x2013;2&#x2013;2</td>
</tr>
<tr>
<td align="left" rowspan="9">Scan QR code to learn how to reconstitute LAmB<break/><break/><inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="HIVMED-27-1789-i001.tif"/></td>
<td align="center">51&#x2013;55</td>
<td align="center">550</td>
<td align="center">11</td>
<td align="center">137.5 mL</td>
<td align="left" rowspan="9">Scan QR code to learn how to manage renal and blood toxicity<break/><break/><inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="HIVMED-27-1789-i002.tif"/></td>
<td align="center">50&#x2013;54</td>
<td align="center">5000</td>
<td align="center">10</td>
<td align="center">3&#x2013;2&#x2013;3&#x2013;2</td>
</tr>
<tr>
<td align="center">56&#x2013;60</td>
<td align="center">600</td>
<td align="center">12</td>
<td align="center">150 mL</td>
<td align="center">55&#x2013;59</td>
<td align="center">5500</td>
<td align="center">11</td>
<td align="center">3&#x2013;3&#x2013;3&#x2013;2</td>
</tr>
<tr>
<td align="center">61&#x2013;65</td>
<td align="center">650</td>
<td align="center">13</td>
<td align="center">162.5 mL</td>
<td align="center">60&#x2013;64</td>
<td align="center">6000</td>
<td align="center">12</td>
<td align="center">3&#x2013;3&#x2013;3&#x2013;3</td>
</tr>
<tr>
<td align="center">66&#x2013;70</td>
<td align="center">700</td>
<td align="center">14</td>
<td align="center">175 mL</td>
<td align="center">65&#x2013;69</td>
<td align="center">6500</td>
<td align="center">13</td>
<td align="center">4&#x2013;3&#x2013;3&#x2013;3</td>
</tr>
<tr>
<td align="center">71&#x2013;75</td>
<td align="center">750</td>
<td align="center">15</td>
<td align="center">187.5 mL</td>
<td align="center">70&#x2013;74</td>
<td align="center">7000</td>
<td align="center">14</td>
<td align="center">4&#x2013;3&#x2013;4&#x2013;3</td>
</tr>
<tr>
<td align="center">76&#x2013;80</td>
<td align="center">800</td>
<td align="center">16</td>
<td align="center">200 mL</td>
<td align="center">75&#x2013;79</td>
<td align="center">7500</td>
<td align="center">15</td>
<td align="center">4&#x2013;4&#x2013;4&#x2013;3</td>
</tr>
<tr>
<td align="center">81&#x2013;85</td>
<td align="center">850</td>
<td align="center">17</td>
<td align="center">212.5 mL</td>
<td align="center">80&#x2013;84</td>
<td align="center">8000</td>
<td align="center">16</td>
<td align="center">4&#x2013;4&#x2013;4&#x2013;4</td>
</tr>
<tr>
<td align="center">86&#x2013;90</td>
<td align="center">900</td>
<td align="center">18</td>
<td align="center">225 mL</td>
<td align="center">85&#x2013;89</td>
<td align="center">8500</td>
<td align="center">17</td>
<td align="center">5&#x2013;4&#x2013;4&#x2013;4</td>
</tr>
<tr>
<td align="center">91&#x2013;95</td>
<td align="center">950</td>
<td align="center">19</td>
<td align="center">237.5 mL</td>
<td align="center">90&#x2013;94</td>
<td align="center">9000</td>
<td align="center">18</td>
<td align="center">5&#x2013;4&#x2013;5&#x2013;4</td>
</tr>
<tr>
<td align="left" colspan="5">Administer in 1 L of 5&#x0025; dextrose fluid over 2 h For weights &#x003E; 95 kg, calculate dose: 10 mg x weight (kg), then <bold><italic>round up</italic></bold> to next 50 mg</td>
<td align="left" colspan="5">For weights &#x2265; 95 kg, calculate dose: 100 mg &#x00D7; weight (kg), then <bold><italic>round down</italic></bold> to next 500 mg/day</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p><italic>Source:</italic> Adapted from the SHARE-CM/IMPRINT project teaching material. Available from <ext-link ext-link-type="uri" xlink:href="https://www.differentiatedservicedelivery.org/resources/the-global-advanced-hiv-disease-toolkit/">https://www.differentiatedservicedelivery.org/resources/the-global-advanced-hiv-disease-toolkit/</ext-link><sup><xref ref-type="bibr" rid="CIT0006">6</xref></sup></p></fn>
<fn><p>IV, intravenous.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T0004">
<label>TABLE 4</label>
<caption><p>Simplified dosing of flucytosine, and simplified dosing and infusion of LAmB using a 200 mL bag of 5&#x0025; dextrose for children and adolescents &#x003C; 40 kg.</p></caption>
<table frame="hsides" rules="groups">
<thead >
<tr>
<th valign="top" colspan="5" align="left">Flucytosine<hr/></th>
<th valign="top" align="center" colspan="9">Liposomal amphotericin B (LAmB)<hr/></th>
</tr>
<tr>
<th valign="top" align="left">Patient weight (kg)</th>
<th valign="top" align="center">Total daily dose (mg)</th>
<th valign="top" align="center">Number of 500 mg pills needed per day</th>
<th valign="top" align="center">Set of 500 mg/tablet flucytosine pills taken per mouth</th>
<th valign="top" align="center">Millilitres of 10 mg/mL solution taken four times a day</th>
<th valign="top" align="center">(A) Weight (kg)</th>
<th valign="top" align="center">(B) Number vials of to reconstitute</th>
<th valign="top" align="center">(C) Volume of 5&#x0025; dextrose to be removed from 200 mL bag</th>
<th valign="top" align="center">(D) mL of reconstituted LAmB</th>
<th valign="top" align="center">(E) Total volume to be infused</th>
<th valign="top" align="center">(F) Infusion</th>
<th valign="top" align="center">(G) Infusion rate</th>
<th valign="top" align="center">Dose in mg</th>
<th valign="top" align="center">Patient weight (kg)</th>
</tr>
</thead>
<tbody >
<tr>
<td align="left">5&#x2013;6</td>
<td align="center">600</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">15 mL</td>
<td align="center">5&#x2013;6</td>
<td align="center">2</td>
<td align="center">116</td>
<td align="center">16</td>
<td align="center">100 mL</td>
<td align="center">4</td>
<td align="center">25 mL/h</td>
<td align="center">62.5</td>
<td align="center">5&#x2013;6</td>
</tr>
<tr>
<td align="left">7&#x2013;8</td>
<td align="center">800</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">20 mL</td>
<td align="center">7&#x2013;8</td>
<td align="center">2</td>
<td align="center">122</td>
<td align="center">22</td>
<td align="center">100 mL</td>
<td align="center">4</td>
<td align="center">25 mL /h</td>
<td align="center">87.5</td>
<td align="center">7&#x2013;8</td>
</tr>
<tr>
<td align="left">9&#x2013;10</td>
<td align="center">1000</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">25 mL</td>
<td align="center">9&#x2013;10</td>
<td align="center">2</td>
<td align="center">125</td>
<td align="center">25</td>
<td align="center">100 mL</td>
<td align="center">2</td>
<td align="center">20 mL /h</td>
<td align="center">100</td>
<td align="center">9&#x2013;10</td>
</tr>
<tr>
<td align="left">11&#x2013;12</td>
<td align="center">1200</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">30 mL</td>
<td align="center">11&#x2013;12</td>
<td align="center">3</td>
<td align="center">132</td>
<td align="center">32</td>
<td align="center">100 mL</td>
<td align="center">2</td>
<td align="center">20 mL /h</td>
<td align="center">125</td>
<td align="center">11&#x2013;12</td>
</tr>
<tr>
<td align="left">13&#x2013;14</td>
<td align="center">1400</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">35 mL</td>
<td align="center">13&#x2013;14</td>
<td align="center">3</td>
<td align="center">137.5</td>
<td align="center">37.5</td>
<td align="center">100 mL</td>
<td align="center">2</td>
<td align="center">20 mL /h</td>
<td align="center">150</td>
<td align="center">13&#x2013;14</td>
</tr>
<tr>
<td align="left">15&#x2013;16</td>
<td align="center">1600</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">40 mL</td>
<td align="center">15&#x2013;16</td>
<td align="center">3</td>
<td align="center">137.5</td>
<td align="center">37.5</td>
<td align="center">100 mL</td>
<td align="center">2</td>
<td align="center">20 mL /h</td>
<td align="center">150</td>
<td align="center">15&#x2013;16</td>
</tr>
<tr>
<td align="left">17&#x2013;20</td>
<td align="center">2000</td>
<td align="center">4</td>
<td align="center">1&#x2013;1&#x2013;1&#x2013;1</td>
<td align="center">-</td>
<td align="center">17&#x2013;20</td>
<td align="center">4</td>
<td align="center">50</td>
<td align="center">50</td>
<td align="center">200 mL</td>
<td align="center">4</td>
<td align="center">50 mL /h</td>
<td align="center">200</td>
<td align="center">17&#x2013;20</td>
</tr>
<tr>
<td align="left">21&#x2013;26</td>
<td align="center">2500</td>
<td align="center">5</td>
<td align="center">2&#x2013;1&#x2013;1&#x2013;1</td>
<td align="center">-</td>
<td align="center">21&#x2013;26</td>
<td align="center">5</td>
<td align="center">62.5</td>
<td align="center">62.5</td>
<td align="center">200 mL</td>
<td align="center">4</td>
<td align="center">50 mL /h</td>
<td align="center">250</td>
<td align="center">21&#x2013;26</td>
</tr>
<tr>
<td align="left">27&#x2013;30</td>
<td align="center">3000</td>
<td align="center">6</td>
<td align="center">2&#x2013;1&#x2013;2&#x2013;1</td>
<td align="center">-</td>
<td align="center">27&#x2013;30</td>
<td align="center">6</td>
<td align="center">75</td>
<td align="center">75</td>
<td align="center">200 mL</td>
<td align="center">2</td>
<td align="center">100 mL /h</td>
<td align="center">300</td>
<td align="center">27&#x2013;30</td>
</tr>
<tr>
<td align="left">31&#x2013;32</td>
<td align="center">3500</td>
<td align="center">7</td>
<td align="center">2&#x2013;2&#x2013;2&#x2013;1</td>
<td align="center">-</td>
<td align="center">31&#x2013;32</td>
<td align="center">6</td>
<td align="center">75</td>
<td align="center">75</td>
<td align="center">200 mL</td>
<td align="center">2</td>
<td align="center">100 mL /h</td>
<td align="center">300</td>
<td align="center">31&#x2013;32</td>
</tr>
<tr>
<td align="left">33&#x2013;36</td>
<td align="center">3500</td>
<td align="center">7</td>
<td align="center">2&#x2013;2&#x2013;2&#x2013;1</td>
<td align="center">-</td>
<td align="center">33&#x2013;36</td>
<td align="center">7</td>
<td align="center">87.5</td>
<td align="center">87.5</td>
<td align="center">200 mL</td>
<td align="center">2</td>
<td align="center">100 mL /h</td>
<td align="center">350</td>
<td align="center">33&#x2013;36</td>
</tr>
<tr>
<td align="left">37&#x2013;40</td>
<td align="center">4000</td>
<td align="center">8</td>
<td align="center">2&#x2013;2&#x2013;2&#x2013;2</td>
<td align="center">-</td>
<td align="center">37&#x2013;40</td>
<td align="center">8</td>
<td align="center">100</td>
<td align="center">100</td>
<td align="center">200 mL</td>
<td align="center">2</td>
<td align="center">100 mL /h</td>
<td align="center">400</td>
<td align="center">37&#x2013;40</td>
</tr>
<tr>
<td align="left" colspan="5">Where possible suspensions should be made up by a pharmacist. Make a 10 mg/mL solution by adding 2 &#x00D7; 500 mg in 100 mL of sterile water (10 mg/mL). The solution should be refrigerated, protected from light and not be kept for more than 7 days.</td>
<td align="left" colspan="9"><list list-type="order">
<list-item><p>Find the appropriate weight band <bold>(A)</bold></p></list-item>
<list-item><p>Identify the number of vials <bold>(B)</bold> needed and reconstitute each vail with 12 mL of sterile water</p></list-item>
<list-item><p>Take a 200 mL bag of 5&#x0025; dextrose</p></list-item>
<list-item><p>Remove the appropriate volume of 5&#x0025; dextrose from the 5&#x0025; dextrose bag <bold>(C)</bold></p></list-item>
<list-item><p>Add the volume of LAmB needed <bold>(D)</bold> to the 200 mL bag of 5&#x0025; dextrose and discard excess LAmB, where appropriate.</p></list-item>
<list-item><p>The total volume to be infused is <bold>(E)</bold> and the infusion time <bold>(F)</bold> and set infusion rate <bold>(G)</bold></p></list-item>
</list></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p>LAmB, liposomal amphotericin B.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s20004">
<title>LAmB toxicity prevention and management</title>
<p>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 &#x003C; 13 years, and weighing &#x003C; 40 kg is 10 mL/kg &#x2013; 15 mL/kg, with a maximum volume of 1 L over 2&#x2013;4 h. The child&#x2019;s weight and nutrition status should be considered when deciding on the infusion rate.</p>
<p>Pre-emptive potassium and magnesium oral supplementation is advised for the first 3 days, unless baseline testing identifies hyperkalaemia (K+ &#x003E; 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.</p>
<p>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 &#x2013; 2 mEq/kg/day (75 mg/kg/day &#x2013; 150 mg/kg/day) of potassium divided into 2&#x2013;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&#x0025; can be used <bold><italic>orally</italic></bold> at 0.2 mL/kg as a once daily dose.</p>
<p>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&#x0025; dextrose after the infusion, and removing or re-siting the line if there is redness or discomfort.</p>
</sec>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<sec id="s20005" sec-type="COI-statement">
<title>Competing interests</title>
<p>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.</p>
</sec>
<sec id="s20006">
<title>CRediT authorship contribution</title>
<p>Nelesh P. Govender: Conceptualisation, writing &#x2013; original draft, writing &#x2013; review &#x0026; editing, supervision. Graeme Meintjes: Conceptualisation, writing &#x2013; original draft, writing &#x2013; review &#x0026; editing. Jonathan Falconer: Writing &#x2013; original draft, writing &#x2013; review &#x0026; editing. Kyla Murphy: Writing &#x2013; original draft, writing &#x2013; review &#x0026; editing. Jeremy S. Nel: Writing &#x2013; original draft, writing &#x2013; review &#x0026; editing. Helena Rabie: Writing &#x2013; review &#x0026; editing. Lisa Frigati: Writing &#x2013; original draft, writing &#x2013; review &#x0026; editing. Denasha L. Reddy: Writing &#x2013; review &#x0026; editing. Halima Dawood: Writing &#x2013; review &#x0026; editing. Ebrahim Variava: Writing &#x2013; review &#x0026; editing. Samantha Potgieter: Writing &#x2013; review &#x0026; editing. Tom Boyles: Writing &#x2013; review &#x0026; editing. Sarah L. Stacey: Writing &#x2013; review &#x0026; editing. Petho Mangena: Writing &#x2013; review &#x0026; editing. Matamela C. Madua: Writing &#x2013; review &#x0026; editing. Camilla Wattrus: Writing &#x2013; review &#x0026; editing and project management. Mahomed-Yunus S. Moosa: Writing &#x2013; review &#x0026; 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.</p>
</sec>
<sec id="s20007">
<title>Ethical considerations</title>
<p>This guideline does not contain any studies involving human participants performed by any of the authors.</p>
</sec>
<sec id="s20008" sec-type="data-availability">
<title>Data availability</title>
<p>Data sharing is not applicable to this article as no new data were created or analysed.</p>
</sec>
<sec id="s20009">
<title>Disclaimer</title>
<p>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.</p>
</sec>
</ack>
<ref-list id="references">
<title>References</title>
<ref id="CIT0001"><label>1</label><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>World Health Organization</collab></person-group>. <source>Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV</source>. <publisher-loc>Geneva</publisher-loc>: <publisher-name>World Health Organization</publisher-name>; <year>2022</year>.</mixed-citation></ref>
<ref id="CIT0002"><label>2</label><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>National Department of Health, Essential Drugs Programme</collab></person-group>. <source>Standard treatment guidelines and essential medicines list for South Africa: hospital level, adults, 2024 edition</source>. <publisher-loc>Pretoria</publisher-loc>: <publisher-name>National Department of Health</publisher-name>; <year>2024</year>.</mixed-citation></ref>
<ref id="CIT0003"><label>3</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Jarvis</surname> <given-names>JN</given-names></string-name>, <string-name><surname>Lawrence</surname> <given-names>DS</given-names></string-name>, <string-name><surname>Meya</surname> <given-names>DB</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Single-dose liposomal amphotericin B treatment for cryptococcal meningitis</article-title>. <source>N Engl J Med</source>. <year>2022</year>;<volume>386</volume>(<issue>12</issue>):<fpage>1109</fpage>&#x2013;<lpage>20</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1056/NEJMoa2111904">https://doi.org/10.1056/NEJMoa2111904</ext-link></comment></mixed-citation></ref>
<ref id="CIT0004"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Govender</surname> <given-names>NP</given-names></string-name>, <string-name><surname>Meintjes</surname> <given-names>G</given-names></string-name>, <string-name><surname>Mangena</surname> <given-names>P</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Southern African HIV Clinicians Society guideline for the prevention, diagnosis and management of cryptococcal disease among HIV-infected persons: 2019 update</article-title>. <source>S Afr J HIV Med</source>. <year>2019</year>;<volume>20</volume>(<issue>1</issue>):<fpage>1030</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4102/sajhivmed.v20i1.1030">https://doi.org/10.4102/sajhivmed.v20i1.1030</ext-link></comment></mixed-citation></ref>
<ref id="CIT0005"><label>5</label><mixed-citation publication-type="book"><person-group person-group-type="author"><string-name><surname>Gilbert</surname> <given-names>DN</given-names></string-name>, <string-name><surname>Eliopoulos</surname> <given-names>GM</given-names></string-name>, <string-name><surname>Chambers</surname> <given-names>HF</given-names></string-name>, <etal>et al</etal>., editors</person-group>. <source>Sanford guide to antimicrobial therapy 2024</source>. <edition>54th</edition> ed. <publisher-loc>Sperryville, VA</publisher-loc>: <publisher-name>Antimicrobial Therapy, Inc.</publisher-name>; <year>2024</year>.</mixed-citation></ref>
<ref id="CIT0006"><label>6</label><mixed-citation publication-type="web"><person-group person-group-type="author"><collab>International Aids Society</collab></person-group>. <source>Global AHD toolkit [homepage on the Internet]</source>. <comment>[cited 2026 Feb 16]. Available from: <ext-link ext-link-type="uri" xlink:href="https://www.differentiatedservicedelivery.org/resources/the-global-advanced-hiv-disease-toolkit/">https://www.differentiatedservicedelivery.org/resources/the-global-advanced-hiv-disease-toolkit/</ext-link></comment></mixed-citation></ref>
</ref-list>
<fn-group>
<fn><p><bold>How to cite this article:</bold> Govender N.P, Meintjes G, Falconer J, et al. SAHCS Guideline for the prevention, diagnosis and management of cryptococcal disease among persons living with HIV: Update to induction treatment for cryptococcal meningitis. S Afr J HIV Med. 2026;27(1), a1789. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4102/sajhivmed.v27i1.1789">https://doi.org/10.4102/sajhivmed.v27i1.1789</ext-link></p></fn>
<fn><p><bold>Note:</bold> Additional supporting information may be found in the online version of this article as Online Appendix 1.</p></fn>
</fn-group>
</back>
</article>