Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
Last Updated: November 6, 2013; Last Reviewed: November 6, 2013
|Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children† with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children† from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children† from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion
†Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents
|Indication||First Choice||Alternative||Comments/Special Issues|
||Fluconazole 6 mg/kg body weight (maximum 200 mg) by mouth once daily||Itraconazole oral solution 5 mg/kg body weight (maximum 200 mg) by mouth once daily||Secondary Prophylaxis Indicated:
If All of the Following Criteria are Fulfilled:
Acute Therapy (Minimum 2-Week Induction Followed by Consolidation Therapy):
Acute Therapy (Minimum 2-Week Induction Followed by Consolidation Therapy)
If Flucytosine Not Tolerated or Unavailable:
Consolidation Therapy (followed by secondary prophylaxis):
|In patients with meningitis, CSF culture should be negative prior to initiating consolidation therapy.
Overall, in vitro resistance to antifungal agents used to treat cryptococcosis remains uncommon. Newer azoles (voriconazole, posaconazole, ravuconazole) are all very active in vitro against C. neoformans, but published clinical experience on their use for cryptococcosis is limited.
Liposomal amphotericin and amphotericin B lipid complex are especially useful for children with renal insufficiency or infusion-related toxicity to amphotericin B deoxycholate.
Liposomal amphotericin and amphotericin B lipid complex are significantly more expensive than amphotericin B deoxycholate.
Liquid preparation of itraconazole (if tolerated) is preferable to tablet formulation because of better bioavailability, but it is more expensive. Bioavailability of the solution is better than the capsule, but there were no upfront differences in dosing range based on preparation used. Ultimate dosing adjustments should be guided by itraconazole levels.
Serum itraconazole concentrations should be monitored to optimize drug dosing.
Amphotericin B may increase toxicity of flucytosine by increasing cellular uptake, or impair its renal excretion, or both.
Flucytosine dose should be adjusted to keep 2-hour post-dose drug levels at 40–60 μg/mL
Oral acetazolamide should not be used for reduction of ICP in cryptococcal meningitis.
Corticosteroids and mannitol have been shown to be ineffective in managing ICP in adults with cryptococcal meningitis.
Secondary prophylaxis is recommended following completion of initial therapy (induction plus consolidation)—drugs and dosing listed above.
|Localized Disease, Including Isolated Pulmonary Disease (CNS Not Involved)b:
||Localized Disease Including Isolated Pulmonary Disease (CNS Not Involved)b:
|Disseminated Disease (CNS Not Involved) or Severe, Pulmonary Diseaseb:
||Disseminated disease (CNS not involved) or severe, pulmonary diseaseb
|a Secondary prophylaxis is also referred to as maintenance therapy or suppressive therapy.
b Duration of therapy for non-CNS disease depends on site and severity of infection and clinical response
Key to Acronyms: cART = combination antiretroviral therapy; CNS = central nervous system; CSF = cerebrospinal fluid; ICP = intracranial pressure; IV = intravenous