What are the guidelines to start dexamethasone for a child diagnosed with Tuberculosis (TB) and Human Immunodeficiency Virus (HIV)?

Dexamethasone for Pediatric TB-HIV Co-infection

Adjunctive corticosteroid therapy with dexamethasone is indicated for children with CNS tuberculosis (tuberculous meningitis) regardless of HIV status, and should be initiated immediately upon starting anti-tuberculosis treatment. 1

Specific Indications for Dexamethasone

For CNS Disease (Tuberculous Meningitis):

• Dexamethasone is strongly recommended for all children with tuberculous meningitis, including those co-infected with HIV 1, 2
• The recommendation applies regardless of disease severity, though greatest mortality benefit is demonstrated in Stage II (lethargic) patients 2

For Other TB Manifestations:

• Dexamethasone can be considered (but is not mandatory) for children with pleural or pericardial effusions, severe miliary disease, and significant endobronchial disease 1
• Steroids are advised for airway obstruction and pericardial TB 1

Dosing Regimen

Weight-Based Dosing:

• Children weighing ≥25 kg: 12 mg/day initially 2
• Children weighing <25 kg: 8 mg/day initially 2

Duration and Tapering:

• Give full dose for 3 weeks 2
• Then taper gradually over the following 3 weeks 2
• Total treatment duration: 6-8 weeks 2, 3

Timing of Initiation

Immediate Start with Anti-TB Treatment:

• Dexamethasone should be initiated concurrently with the 4-drug anti-tuberculosis regimen (isoniazid, rifampin, pyrazinamide, and ethambutol) 2
• Do not delay corticosteroid therapy while awaiting microbiological confirmation 3

Critical Considerations for HIV Co-infection

Evidence Limitations:

• While dexamethasone has proven mortality benefit in HIV-negative patients with TBM, the evidence in HIV-infected patients remains uncertain 4, 5, 6
• One major trial showed immediate ART initiation in HIV-associated TBM did not improve outcomes and caused more grade 4 adverse events 7
• Despite this uncertainty, current guidelines recommend dexamethasone for all children with CNS TB regardless of HIV status 1, 3

Antiretroviral Therapy Timing:

• For HIV co-infected children with TB, initiate ART within 2 weeks of starting TB therapy (not immediately) 1
• This timing reduces adverse drug reactions while allowing rapid immune restoration 1
• Monitor closely for Immune Reconstitution Inflammatory Syndrome (IRIS), which may respond to corticosteroids 1

Anti-Tuberculosis Treatment Regimen

Intensive Phase (2 months):

• Isoniazid: 10-15 mg/kg/day (max 300 mg) 1
• Rifampin: 10-20 mg/kg/day (max 600 mg) 1
• Pyrazinamide: 20-40 mg/kg/day (max 2 g) 1
• Ethambutol: 15-25 mg/kg/day (max 2.5 g) 1

Continuation Phase:

• Isoniazid + Rifampin for 7-10 additional months 2, 4
• Total treatment duration for HIV co-infected children: 9-12 months 1, 4

Critical Dosing Considerations:

• Use daily dosing (not intermittent) for HIV co-infected children 4
• Twice-weekly regimens should NOT be used in severely immunosuppressed children (CD4 <15% or <100 cells/μL if ≥6 years old) due to risk of rifamycin resistance 1

Essential Adjunctive Therapy

Pyridoxine Supplementation:

• Mandatory for all HIV-infected children receiving TB treatment 1
• Also required if child is malnourished, breastfed, or receiving cycloserine/terizidone 1

Nutritional Support:

• Most children with TB are malnourished and require multivitamin supplements 1
• Assess and address high caloric requirements due to ongoing inflammation 1

Monitoring Requirements

CSF Parameters:

• Perform repeated lumbar punctures to monitor cell count, glucose, and protein, especially early in therapy 2, 4

Drug Levels:

• Consider monitoring rifampin blood levels if poor treatment response occurs, as malabsorption is possible in HIV co-infection 4

Renal Function:

• If using tenofovir in ART regimen, monitor renal function and electrolytes regularly 1

Common Pitfalls to Avoid

• Do not delay dexamethasone while awaiting diagnostic confirmation in suspected TBM 3
• Do not use twice-weekly TB regimens in immunosuppressed HIV-infected children 1
• Do not start ART immediately with TB treatment; wait 2 weeks to reduce adverse events 1, 7
• Do not omit pyridoxine in HIV-infected children on TB treatment 1
• Do not use stavudine in ART regimen for children on TB treatment 1