What is the recommended dosage of lamivudine (3TC) plus zidovudine (AZT) for a pediatric patient with Human Immunodeficiency Virus (HIV) infection?

Recommended Dosage of Lamivudine Plus Zidovudine for Pediatric HIV Patients

For pediatric patients with HIV infection, lamivudine should be dosed at 4 mg/kg orally twice daily (maximum 150 mg per dose) and zidovudine at 180 mg/m² every 12 hours (or 90 mg/m² every 12 hours for mild to moderate disease), both administered as part of a fully suppressive antiretroviral regimen. 1, 2

Weight-Based Dosing for Lamivudine

• Lamivudine: 4 mg/kg body weight orally twice daily, with a maximum dose of 150 mg per dose 1
• This dosing applies when lamivudine is used as part of combination antiretroviral therapy (HAART) for HIV treatment 1
• For children old enough to receive adult dosing, the standard adult dose is 150 mg twice daily 1

Body Surface Area-Based Dosing for Zidovudine

• Standard dose: 180 mg/m² body surface area every 12 hours 2
• Alternative lower dose for mild to moderate disease: 90 mg/m² every 12 hours 2
• The lower dose (90 mg/m²) was shown to be equally effective as the higher dose in children with mild to moderate HIV symptoms, with no difference in efficacy, survival, or disease progression 2
• The lower dose provides substantial cost savings while maintaining therapeutic efficacy 2

Critical Dosing Requirements

Both medications MUST be administered twice daily (every 12 hours) to maintain therapeutic drug levels. 3, 4

• Zidovudine has a relatively short half-life requiring multiple daily doses 4
• Once-daily dosing leads to subtherapeutic drug levels, particularly for zidovudine, resulting in virologic failure and development of drug resistance 3, 4
• No clinical guidelines support once-daily dosing of this combination 4

Fixed-Dose Combination Option (Combivir)

• Combivir tablets contain zidovudine 300 mg + lamivudine 150 mg 4
• Dosing: One tablet twice daily (every 12 hours) 4
• This formulation is appropriate for older children who can swallow tablets and meet weight requirements for adult dosing 4

Weight-Band Simplified Dosing Considerations

For resource-limited settings where body surface area calculations are impractical, weight-based dosing charts can be used: 5

• For children <20 kg: Weight-based dosing of zidovudine solution provides reasonable precision (median difference -6.4% compared to BSA-based dosing) 5
• For children ≥20 kg: Weight-based dosing is highly accurate (median difference 0.0% for solution) 5
• Caution: Zidovudine capsules in children <20 kg result in underdosing >20% in 27.2% of cases; liquid formulation is preferred for this weight range 5

Renal Dose Adjustments for Lamivudine

For patients with renal insufficiency, lamivudine requires dose reduction: 1

• Creatinine clearance 30-49 mL/min: 100 mg first dose, then 50 mg once daily
• Creatinine clearance 15-29 mL/min: 35 mg first dose, then 25 mg once daily
• Creatinine clearance 5-14 mL/min: 35 mg first dose, then 15 mg once daily
• Creatinine clearance <5 mL/min: 35 mg first dose, then 10 mg once daily

Special Considerations for HIV/HBV Coinfection

When treating both HIV and hepatitis B virus: 1

• The same lamivudine dose (4 mg/kg twice daily, max 150 mg/dose) provides dual activity against both viruses 1
• Lamivudine must be part of a fully suppressive HAART regimen to prevent resistance 1
• Critical warning: If lamivudine is discontinued in HBV-coinfected patients, hepatitis flares can occur and may be life-threatening; reinstitution of therapy is recommended 1

Monitoring Requirements

• HIV RNA viral load testing at 2-4 weeks (ideally by 6 weeks) to confirm early virologic response 3
• Goal: Undetectable viral load (<50 copies/mL) by 12-24 weeks 3
• Continue monitoring every 3 months until viral load <50 copies/mL for at least one year, then every 6 months 3
• Monitor renal function (creatinine, eGFR) and hepatic function tests (ALT, AST) at baseline and ongoing 3

Management of Common Adverse Effects

Do not discontinue zidovudine prematurely due to mild gastrointestinal side effects. 3, 6

• Gastrointestinal disturbances are the most common adverse events but are usually manageable with antiemetics and antimotility agents 7
• These side effects often improve over time with continued therapy 3
• Premature discontinuation risks treatment failure and resistance development 3

Important Pitfalls to Avoid

• Never attempt once-daily dosing of this combination—it guarantees treatment failure 6, 4
• Never use zidovudine capsules in children <20 kg due to high risk of underdosing; use liquid formulation instead 5
• Never add a single active agent to a failing regimen; perform resistance testing and change the complete regimen 6
• In children with advanced disease (CD4+ <100 cells/μL), monitor closely for pancreatitis, though causality with lamivudine is unclear 7