What is the recommended antiretroviral therapy (Anti-Retroviral Therapy) for a child under 2 years of age?

Recommended Antiretroviral Therapy for Children Under 2 Years of Age

For children under 2 years of age, the recommended antiretroviral therapy is a combination regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor, specifically using nelfinavir or ritonavir as the protease inhibitor component due to their available pediatric formulations. 1

Rationale for Combination Therapy

Combination therapy is essential for several key reasons:

• Slows disease progression and improves survival
• Results in greater and more sustained virologic response
• Delays development of viral resistance to the drugs being used

Monotherapy is no longer recommended for treating HIV infection in any age group, including infants and young children 1.

Specific Drug Recommendations for Children Under 2 Years

Protease Inhibitor Options:

• Nelfinavir (Viracept®): Available as a powder formulation that can be mixed with water or food
• Ritonavir (Norvir®): Available as a liquid formulation

Both of these protease inhibitors have formulations appropriate for infants and children who cannot swallow pills, making them suitable for children under 2 years of age 1.

NRTI Backbone Options:

The recommended NRTI backbone typically consists of:

• Zidovudine (ZDV) and lamivudine as the preferred NRTI combination 1, 2

Clinical Evidence Supporting This Approach

The aggressive three-drug antiretroviral therapy approach for primary perinatal infection is recommended because it provides the best opportunity to:

1. Preserve immune function
2. Delay disease progression
3. Maximize viral suppression, preferably to undetectable levels 1

Clinical trials have demonstrated that therapy with drug combinations that include a protease inhibitor is more effective than therapy with two NRTI antiretroviral drugs alone in reducing viral load to undetectable levels and increasing CD4+ T-lymphocyte numbers 1.

Special Considerations for Children Under 2 Years

Monitoring Parameters:

• CD4+ T cell percentage (rather than absolute count) is the preferred marker of immunological status in children under 5 years 2
• HIV RNA levels should be monitored at least every 3 months to evaluate response to therapy 1
• A substantial increase in HIV RNA (more than 0.7 log10 or fivefold increase for children under 2 years) warrants consideration of therapy modification 1

Efficacy Data:

In the IMPAACT P1066 study evaluating raltegravir in infants and toddlers 4 weeks to less than 2 years of age:

• At Week 24,39% achieved HIV RNA <50 copies/mL and 61% achieved HIV RNA <400 copies/mL
• Mean CD4 count increase from baseline to Week 24 was 500 cells/mm³ (7.5%) 3

Important Caveats and Pitfalls

1. Adherence challenges: Issues with adherence are especially important in young children who depend on caregivers for medication administration. Participation by caregivers in the decision-making process is crucial 1.

2. Formulation limitations: Some protease inhibitors like indinavir and saquinavir are not available in liquid formulations, limiting their use in young children who cannot swallow pills 1.

3. Taste acceptability: The lopinavir+ritonavir combination, while effective, has poor acceptance by children due to unpleasant taste and high ethanol content in the ritonavir oral solution 2.

4. Optimal dosing uncertainty: Optimal dosing of protease inhibitors in children under 2 years is still being evaluated in clinical trials 1.

5. Resistance development: Lack of adherence to prescribed regimens and subtherapeutic levels of antiretroviral medications may enhance the development of drug resistance 1.

By following these recommendations and carefully monitoring response to therapy, clinicians can optimize outcomes for HIV-infected children under 2 years of age, reducing morbidity and mortality while preserving quality of life.