What is the recommended antiretroviral therapy (ART) regimen for pediatric patients with Human Immunodeficiency Virus (HIV)?

Recommended Antiretroviral Therapy Regimen for Pediatric HIV Patients

The recommended antiretroviral therapy (ART) for pediatric HIV patients is a combination therapy with three drugs, including two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor, initiated as early as possible after diagnosis, especially in infants under 12 months regardless of clinical or immunologic status. 1

Timing of ART Initiation

Infants (<12 months)

• Immediate initiation upon confirmed diagnosis regardless of:
  • Clinical symptoms
  • Immunologic status (CD4+ count/percentage)
  • Viral load
• Rationale: Infants are at high risk for disease progression, and early therapy provides the best opportunity to preserve immune function and delay disease progression 1, 2
• Early treatment (within first 6 months) is associated with better sustained virologic control after initial suppression 2

Children 1-5 years

• Treatment recommended for:
  • All children with clinical symptoms (CDC clinical categories A, B, or C)
  • Children with evidence of immune suppression (immune categories 2 or 3)
  • Children with HIV RNA levels >100,000 copies/mL (high mortality risk)
  • Children with substantial increases in HIV RNA levels on repeated testing

    • 0.7 log10 (fivefold) increase for children <2 years

    • 0.5 log10 (threefold) increase for children ≥2 years 1

Recommended ART Regimens

First-line Regimen

• Combination therapy with three drugs:
  • Two NRTIs plus one protease inhibitor 1
  • This combination has been shown to be more effective than dual NRTI therapy in reducing viral load to undetectable levels and increasing CD4+ T-lymphocyte counts 1

Medication Selection Considerations

• For infants and young children who cannot swallow pills:
  • Protease inhibitors with appropriate formulations include:
    • Nelfinavir (powder formulation that can be mixed with water or food)
    • Ritonavir (liquid formulation) 1
  • For NRTIs, lamivudine is available but the scored tablet is preferred over oral solution when possible to avoid potential interaction with sorbitol 3
  • Atazanavir is indicated for children ≥6 years weighing at least 15 kg but not recommended for children <3 months due to risk of kernicterus 4

Monitoring and Management

Virologic Response Monitoring

• Initial assessment: 4 weeks after therapy initiation
• Time to maximal response may vary:
  • 8-12 weeks if baseline HIV RNA >1,000 copies/mL
  • 4 weeks if baseline HIV RNA <100,000 copies/mL
• After maximal response: monitor HIV RNA at least every 3 months 1

Criteria for Considering Regimen Change

• Less than 10-fold (1.0 log10) decrease from baseline HIV RNA after 8-12 weeks of therapy with two NRTIs and a protease inhibitor
• HIV RNA not suppressed to undetectable levels after 4-6 months of therapy
• Repeated detection of HIV RNA after initial undetectable levels
• Reproducible increase in HIV RNA copy number 1

Special Considerations

Adherence Issues

• Critical for successful treatment outcomes
• Intensive education of caregivers and patients before therapy initiation
• Address potential adherence problems, especially for adolescents who may face unique challenges 1, 5

Safety Concerns

• Monitor for potential adverse effects:
  • Lactic acidosis and severe hepatomegaly with steatosis (particularly in females) 3
  • Pancreatitis in pediatric patients with prior antiretroviral exposure 3
  • Immune reconstitution syndrome 3

Evolution of Treatment

• Historical context shows significant evolution from single/dual NRTI regimens to highly active antiretroviral therapy (HAART) 5
• Early initiation of ART in infants has been associated with reduced morbidity and mortality 6

The evidence strongly supports early initiation of combination antiretroviral therapy in HIV-infected children, particularly in infants under 12 months, to maximize the chances of viral suppression, preserve immune function, and improve clinical outcomes.