When is zidovudine (Antiretroviral medication) given to a baby born to an HIV (Human Immunodeficiency Virus)-positive mother?

When to Give Zidovudine to a Baby

Zidovudine should be administered to all infants born to HIV-positive mothers, starting within 6-12 hours of birth and continuing for 6 weeks, with the specific regimen determined by the mother's antiretroviral therapy status and viral load during pregnancy. 1

Standard Prophylaxis for Low-Risk Infants

For infants whose mothers received adequate antiretroviral therapy during pregnancy with viral suppression (<1,000 copies/mL):

• Administer zidovudine 4 mg/kg orally twice daily for 6 weeks 2, 3
• Begin treatment within 6-12 hours of birth for maximum effectiveness 2
• No additional agents (such as nevirapine) are needed in this scenario 3

This represents the standard prophylaxis when maternal HIV is well-controlled with at least 2 years of antiretroviral therapy and documented viral suppression. 3

Enhanced Prophylaxis for High-Risk Infants

For infants whose mothers received no antiretroviral therapy before or during labor:

• Administer single-dose nevirapine 2 mg/kg oral suspension immediately after birth or within 72 hours 1, 2
• PLUS zidovudine 4 mg/kg orally twice daily for 6 weeks 2, 4
• This combination regimen reduces transmission by approximately two-thirds compared to no treatment 1, 5

The combination of nevirapine plus zidovudine has demonstrated superior efficacy compared to single-dose nevirapine alone when mothers have not received antiretroviral drugs. 2, 4

Intermediate-Risk Scenarios

For mothers who received only intrapartum zidovudine (no antepartum therapy):

• Offer the intrapartum and neonatal components of the ACTG Protocol 076 regimen 1
• Administer zidovudine to the infant for 6 weeks starting within 6-12 hours of birth 2
• Consider adding single-dose nevirapine if maternal viral load is elevated or unknown 2, 4

The intravenous route during labor provides predictable maternal levels that result in substantial fetal blood levels during birth, when the infant is presumed to be exposed extensively to HIV through contact with the mother's blood and genital secretions. 1

Critical Timing Considerations

Zidovudine must be initiated within 6-12 hours of birth for optimal effectiveness:

• Transmission rates are 9% when zidovudine is started within 48 hours 2
• Transmission rates increase to 18% when delayed beyond 48 hours 2
• Transmission rates reach 27% with no prophylaxis 2

Animal model data indicate that if zidovudine is to have any effect as postexposure prophylaxis, prompt administration within hours is critical, though even with early initiation such prophylaxis may not be fully protective. 1

The Complete ACTG 076 Regimen

The landmark trial that established zidovudine's efficacy included three components:

• Antepartum: Oral zidovudine 100 mg five times daily starting at 14-34 weeks gestation 1, 5
• Intrapartum: Intravenous zidovudine 2 mg/kg loading dose over 1 hour, then 1 mg/kg/hour until delivery 1, 5
• Neonatal: Oral zidovudine 2 mg/kg every 6 hours for 6 weeks 1, 5

This regimen reduced perinatal HIV transmission from 25.5% to 8.3%, representing a 67.5% relative reduction in transmission risk. 1, 5

Common Pitfalls to Avoid

Do not add nevirapine when maternal antiretroviral therapy is adequate:

• Adding nevirapine to mothers already on adequate antiretroviral therapy provides no additional benefit (transmission rates 1.4% vs 1.6%) 2
• This practice increases resistance risk from 0% to 15-19% 2, 3

Do not use single-dose nevirapine monotherapy:

• Single-dose nevirapine alone carries a 19% risk of resistance mutations at 6 weeks postpartum 2
• Combination therapy with zidovudine is essential to reduce resistance development 2

Do not delay zidovudine initiation:

• Every hour of delay reduces effectiveness 2
• The full 6-week course is necessary; shorter courses (e.g., 1 week) have not proved effective 2

Safety Profile

Zidovudine is generally well-tolerated in neonates:

• Mild anemia occurs in 22% of treated infants versus 12% of placebo recipients 6, 5
• Mean hemoglobin difference is less than 1.0 g/dL 6
• No transfusions are typically required, and hemoglobin values spontaneously normalize within 6 weeks after completing therapy 6, 5
• Neutropenia occurs with similar frequency in treated (21%) and placebo (27%) groups 6
• Macrocytosis is common but resolves by the second month of life 7

The long-term consequences of in utero and infant exposure to zidovudine remain unknown, though short-term and intermediate-term follow-up (up to 5.6 years) has shown the drug to be generally well-tolerated. 6, 8

Alternative Regimens When Zidovudine Is Unavailable

For infants ≥4 weeks to 2 years old when zidovudine cannot be given:

• Dolutegravir plus two NRTIs (emtricitabine or lamivudine) is the preferred alternative 2
• Raltegravir plus two NRTIs is a secondary alternative for infants ≥2 kg 2
• Lopinavir/ritonavir plus two NRTIs is another secondary alternative 2

For neonates aged ≥14 days to <4 weeks, immediate consultation with a pediatric HIV specialist is mandatory through the NCCC PEPline at 888-448-4911. 2