What is the recommended Nevirapine (Nevirapine) dosing regimen for the prevention of parent-to-child transmission (PPTCT) of Human Immunodeficiency Virus (HIV)?

Nevirapine Dosing for Prevention of Parent-to-Child Transmission (PPTCT)

For PPTCT services, administer nevirapine as a single 200 mg oral dose to the mother at onset of labor, combined with a single 2 mg/kg oral dose to the infant immediately after birth (or within 72 hours), preferably as soon as possible after delivery before hospital discharge. 1

Maternal Dosing

• Mother receives 200 mg oral nevirapine as a single dose at the onset of labor 2
• This single dose achieves median plasma concentrations of 1623 ng/ml at delivery, with effective transplacental transfer (cord/maternal blood ratio of 0.75) 3
• The maternal half-life is approximately 61 hours, providing sustained antiretroviral activity for one week postpartum 3

Infant Dosing

• Infant receives 2 mg/kg oral suspension as a single dose immediately after birth or within 48-72 hours 2, 1
• Immediate administration after birth is strongly preferred over waiting 48-72 hours, as many PPTCT programs find this more practical and ensures the infant receives the dose before discharge 2, 1
• This single infant dose maintains plasma nevirapine concentrations above 100 ng/ml (10 times the IC50 against HIV-1) throughout the first week of life 4, 3
• The neonatal half-life is 46.5-54 hours, supporting the single-dose prophylaxis approach 4, 3

Enhanced Regimens for High-Risk Scenarios

When mothers received NO antiretroviral therapy during pregnancy or labor, combine single-dose nevirapine with zidovudine for superior efficacy:

• Infant regimen: Single-dose nevirapine 2 mg/kg at birth PLUS zidovudine 4 mg/kg twice daily for 4-6 weeks 2, 1
• This combination is more efficacious than single-dose nevirapine alone, as demonstrated in the NVAZ trial in Malawi 2, 1
• Alternative: Zidovudine alone for 6 weeks (started within 6-12 hours of birth) if nevirapine is contraindicated 1

Maternal Combination Regimens

For mothers presenting in labor without prior antiretroviral therapy:

• Option 1: Nevirapine 200 mg at onset of labor PLUS zidovudine 600 mg at onset of labor, then zidovudine 300 mg every 3 hours until delivery 2
• Option 2: Nevirapine 200 mg at onset of labor PLUS lamivudine 150 mg at onset of labor and every 12 hours until delivery 2

Clinical Efficacy Data

• The HIVNET 012 single-dose nevirapine regimen reduced transmission by nearly 50% compared to short-course zidovudine (12% vs 21% transmission at 6 weeks) 2
• In optimal conditions (protocol adherence with maternal CD4 >500), transmission rates as low as 7% have been achieved 5
• The combination of single-dose nevirapine with short-course zidovudine provides superior efficacy compared to either agent alone 2

Critical Implementation Points

• Timing is crucial: Administer infant nevirapine as soon as possible after birth, ideally before hospital discharge, rather than waiting for the 48-72 hour window 2, 1
• Use oral dosing syringe: For the infant suspension, use an oral dosing syringe (not a dosing cup) to ensure accurate delivery of the small volume 6
• Shake suspension gently: Nevirapine oral suspension must be shaken gently before administration 6
• Monitor for rash: Approximately half of subjects with symptomatic hepatic adverse events presented with rash, though serious adverse events are rare in the single-dose prophylaxis setting 6, 3

Important Caveats

• Resistance concerns: Single-dose nevirapine can lead to emergence of nevirapine-resistant HIV-1, particularly in women with high baseline viral loads and low CD4 counts 7
• Repeat pregnancies: Despite resistance concerns, repeat single-dose nevirapine in subsequent pregnancies remains effective, with no increased risk of infant HIV infection compared to nevirapine-unexposed women (11.3% vs 16.7% infection rates) 8
• Hepatotoxicity risk: Nevirapine should be used with caution in women with CD4 counts >250/mm³ due to risk of severe hepatic toxicity, though this is primarily a concern with chronic dosing rather than single-dose prophylaxis 9, 6
• Not for occupational PEP: Nevirapine is contraindicated for post-exposure prophylaxis regimens due to hepatotoxicity risk 6

Breastfeeding Considerations

• Nevirapine concentrations in breast milk average 60.5% of maternal plasma levels during the first week, with median concentrations of 103 ng/ml one week after delivery 3
• In resource-rich settings, breastfeeding is not recommended for HIV-infected women regardless of antiretroviral therapy 10
• In resource-limited settings where safe feeding alternatives are unavailable, the single-dose nevirapine regimen provides protection against intrapartum and early breast milk transmission 3