What antiretroviral medications can be used to treat HIV in infants?

Antiretroviral Medications for HIV Treatment in Infants

Preferred Initial Regimen for HIV-Infected Infants

For HIV-infected infants, the preferred initial treatment is aggressive combination antiretroviral therapy with two nucleoside reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor, initiated as early as possible after diagnosis is confirmed. 1

Age-Specific Treatment Recommendations

Infants Under 2 Weeks of Age

• Nevirapine-based regimen is recommended: Nevirapine 6 mg/kg twice daily plus zidovudine (ZDV) plus lamivudine (3TC) 2, 3
• This combination can be safely started in the first week of life, even within the first 2-5 days after birth 2
• Nevirapine dosing requires adjustment in neonates due to prolonged half-life compared to older children 1
• Lamivudine dosing in newborns should be half the dose recommended for older children due to prolonged clearance 1

Infants 2 Weeks to 24 Months of Age

• Lopinavir/ritonavir-based regimen is preferred: Lopinavir/ritonavir plus two NRTIs (typically zidovudine plus lamivudine) 4, 3
• Ritonavir is available in liquid formulation suitable for infants who cannot swallow pills 1
• Nelfinavir powder formulation (can be mixed with water or food) is an alternative protease inhibitor option 1
• Optimal dosing of protease inhibitors in children under 2 years is still being evaluated in clinical trials 1

NRTI Backbone Options

The dual NRTI backbone typically consists of: 1

• Zidovudine (ZDV) - most extensively studied in neonates with established dosing based on pharmacokinetic studies 1
• Lamivudine (3TC) - safety and pharmacokinetics evaluated in newborns, requires dose adjustment 1
• Alternative combinations: ZDV + didanosine (ddI) or ZDV + stavudine have shown clinical benefit 1

Critical Timing Considerations

• Initiate treatment in all HIV-infected infants under 12 months as soon as diagnosis is confirmed, regardless of clinical or immunologic status or viral load 1
• Infants under 12 months are at high risk for rapid disease progression 1
• Early aggressive therapy during the first 1-2 years of life (when viral replication is highest) may preserve immune function and lower the viral set point 1
• If an infant is receiving ZDV monotherapy for prevention of perinatal transmission and is identified as HIV-infected, immediately switch to combination therapy 1

Special Dosing Considerations for Neonates

Zidovudine (ZDV)

• Dosing adjustments required due to immature hepatic glucuronidation in neonates, causing prolonged half-life and clearance 1
• Premature infants (born before 34 weeks gestation) have even greater metabolic immaturity requiring further dose modifications 1
• Appropriate dosing for premature infants is still being evaluated in clinical trials 1

Protease Inhibitors

• Lopinavir/ritonavir oral solution contains ethanol (42% v/v) and propylene glycol (15% w/v) 5
• Should NOT be used in preterm neonates in the immediate postnatal period due to risk of life-threatening cardiac toxicity, lactic acidosis, acute renal failure, CNS depression, and respiratory complications 5
• If used in infants immediately after birth, close monitoring is required for hyperosmolality, lactic acidosis, renal toxicity, CNS depression, seizures, cardiac arrhythmias, and hemolysis 5

Alternative Regimens

When protease inhibitor-based therapy is not feasible due to adherence concerns or caregiver preference: 1

• Two NRTIs plus nevirapine (substituting nevirapine for the protease inhibitor)
• Two NRTIs alone (though less likely to achieve sustained viral suppression)

Important caveat: Alternative regimens may not suppress viral load to undetectable levels as consistently as two NRTIs plus a protease inhibitor, potentially leading to development of viral resistance 1

Drugs NOT Recommended for Infants

• Indinavir and saquinavir - not available in liquid formulations, only for children who can swallow capsules 1
• Saquinavir hard-gel capsule (Invirase) - limited bioavailability, not recommended with two NRTIs 1
• Tenofovir - FDA-approved only for children 12 years and older weighing ≥35 kg 6

Monitoring and Adherence

• Intensive caregiver education about adherence is essential before initiating therapy 1
• Frequent follow-up required to assess virologic response, drug tolerance, and adherence 1
• Poor adherence is a major contributor to virologic failure 2, 4
• Improved palatability of liquid protease inhibitor preparations and behavioral approaches are necessary to improve medication adherence 4

Expected Outcomes

With appropriate three-drug combination therapy initiated early: 2

• 55% of infants achieve HIV RNA <40 copies/mL by 12 weeks
• 71% achieve HIV RNA <40 copies/mL by 24 weeks
• 93% achieve HIV RNA <400 copies/mL by 12 weeks