Recommended ART for High-Risk HIV-Exposed Newborn
This newborn should receive nevirapine in addition to lamivudine and zidovudine (Answer A). This represents a high-risk scenario requiring enhanced prophylaxis due to maternal high viral load (45,000 copies/mL), no prenatal ART, and prematurity with low birth weight.
Risk Stratification and Rationale
This clinical scenario presents multiple high-risk features for perinatal HIV transmission:
- Maternal viral load of 45,000 copies/mL indicates substantial transmission risk 1
- No maternal ART during pregnancy (only intrapartum zidovudine) 2
- Premature delivery at 35 weeks with birthweight 1.8 kg 2
For newborns whose mothers received no antiretroviral therapy before or during labor, the recommended regimen is single-dose nevirapine 2 mg/kg oral suspension immediately after birth PLUS zidovudine for 6 weeks 2. The addition of lamivudine to this regimen creates a three-drug prophylactic approach appropriate for this high-risk exposure.
Evidence Supporting Nevirapine Addition
The superiority of adding nevirapine to dual NRTI prophylaxis is well-established:
- A landmark randomized trial (HPTN 040) demonstrated that zidovudine plus three doses of nevirapine reduced intrapartum HIV transmission to 2.2% compared to 4.8% with zidovudine alone (P=0.046) 1
- Single-dose nevirapine combined with zidovudine has demonstrated superior efficacy compared to single-dose nevirapine alone when mothers have not received antiretroviral drugs 2
- Nevirapine achieves therapeutic concentrations rapidly, with prolonged elimination in neonates (median half-life 36.8-54 hours) supporting single-dose prophylaxis 2, 3
Dosing and Administration
Administer nevirapine 2 mg/kg oral suspension immediately after birth or within 72 hours 2. Giving the dose as soon as possible after birth is critical for effectiveness 2.
The complete regimen for this newborn should be:
- Nevirapine: 2 mg/kg single dose at birth 2
- Zidovudine: 4 mg/kg twice daily for 6 weeks 2
- Lamivudine: 2 mg/kg twice daily for 2 weeks 1
Why Not the Other Options
Lopinavir/ritonavir (Option B) is an alternative agent but not preferred for neonates in this scenario. While it can be used in infants aged ≥4 weeks to 2 years as an alternative regimen 4, nevirapine has more extensive evidence specifically for prevention of mother-to-child transmission in high-risk scenarios 1.
Darunavir/ritonavir (Option C) requires the infant to be ≥3 years old and ≥10 kg for safety and dosing 4, making it inappropriate for this 1.8 kg premature newborn.
Raltegravir (Option D) is listed as an alternative for infants ≥2 kg 4, but nevirapine remains the preferred third agent based on the extensive evidence base for prevention of mother-to-child transmission 1, 2 and the specific WHO recommendations for newborns whose mothers received inadequate prenatal ART 4.
Safety Considerations
No serious adverse events related to nevirapine were observed in multiple studies 2. The most common toxicity is rash, which is usually mild and self-limiting 3. This safety profile is superior to the three-drug regimen with nelfinavir, which showed significantly increased neutropenia rates 1.