Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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Antiretroviral Management of Newborns with Perinatal HIV Exposure or Perinatal HIV

Last Updated: December 14, 2018; Last Reviewed: December 14, 2018

Panel's Recommendations for Antiretroviral Management of Newborns with Perinatal HIV Exposure or Perinatal HIV
Panel's Recommendations
  • All newborns perinatally exposed to HIV should receive postpartum antiretroviral (ARV) drugs to reduce the risk of perinatal transmission of HIV (AI).
  • Newborn ARV regimens—at gestational-age-appropriate doses—should be initiated as close to the time of birth as possible, preferably within 6 to 12 hours of delivery (AII).
  • The selection of a newborn ARV regimen should be determined based on maternal and infant factors that influence risk of perinatal transmission of HIV (AIII). The uses of ARV regimens in newborns include:
    • ARV Prophylaxis: The administration of one or more ARV drugs to a newborn without documented HIV infection to reduce the risk of perinatal acquisition of HIV.
    • Empiric HIV Therapy: The administration of a three-drug ARV regimen to newborns at highest risk of perinatal acquisition of HIV. Empiric HIV therapy is intended to be preliminary treatment for a newborn who is later documented to have HIV but also serves as prophylaxis against HIV acquisition for those newborns who are exposed to HIV in utero, during the birthing process, or during breastfeeding and who do not acquire HIV.
    • HIV Therapy: The administration of a three-drug ARV regimen at treatment dosages (antiretroviral therapy [ART]) to newborns with documented HIV infection (see Diagnosis of HIV Infection).
  • For newborns whose mothers have received ART during pregnancy with sustained viral suppression near delivery and for whom there are no concerns related to maternal adherence, a 4-week zidovudine ARV prophylaxis regimen can be used (BII).
  • Newborns at higher risk of perinatal acquisition of HIV should receive a multi-drug ARV prophylaxis regimen or empiric HIV therapy based on clinician assessment of risk (see Tables 11 and 12 for recommended regimens). Newborns at higher risk of HIV acquisition include those born to women with HIV who:
    • Have not received antepartum or intrapartum ARV drugs (AI), or
    • Have received only intrapartum ARV drugs (AI), or
    • Have received antepartum ARV drugs but without viral suppression near delivery (AII), or
    • Have primary or acute HIV infection during pregnancy (AII), or
    • Have primary or acute HIV infection during breastfeeding (AII).
  • Newborns of women with unknown HIV status who test HIV positive on expedited testing performed during labor or shortly after birth should initiate an ARV regimen (ARV prophylaxis or empiric HIV therapy based on clinician assessment of risk) (AII). If supplemental testing is negative, the ARV regimen can be discontinued (AII).
  • For newborns with HIV infection, ART should be initiated (AI).
  • The use of ARV drugs other than zidovudine, lamivudine, and nevirapine cannot be recommended for any indication in premature newborns (<37 weeks gestational age) because of lack of dosing and safety data (BIII).
  • Providers with questions about ARV management of perinatal HIV exposure should consult the National Perinatal HIV Hotline (1-888-448-8765), which provides free clinical consultation on all aspects of perinatal HIV, including newborn care (AIII).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion

Table 11. Newborn Antiretroviral Management According to Risk of HIV Infection in the Newborn

Drug selection and dosing considerations are related to the age and gestational age of the newborn. Consultation is available through the National Perinatal HIV Hotline (888-448-8765).

Table 11. Newborn Antiretroviral Management According to Risk of HIV Infection in the Newborn
Category Description Neonatal ARV Management
Low Risk of Perinatal HIV Transmission
  • Mothers who received ART during pregnancy with sustained viral suppression near delivery and no concerns related to adherence
ZDV for 4 weeks
Higher Risk of Perinatal HIV Transmissiona,b
  • Mothers who received neither antepartum nor intrapartum ARV drugs
  • Mothers who received only intrapartum ARV drugs
  • Mothers who received antepartum and intrapartum ARV drugs but who have detectable viral load near delivery, particularly if delivery was vaginal
  • Mothers with acute or primary HIV infection during pregnancy or breastfeeding (in which case, the mother should discontinue breastfeeding).c
2-drug ARV prophylaxis (NICHD-HPTN 040/PACTG 1043 regimen) with 6 weeks ZDV and 3 doses of NVP (prophylactic dosage, with doses given within 48 hours of birth, 48 hours after first dose, and 96 hours after second dose)

or

Empiric HIV therapy using either ZDV, 3TC, and NVP (treatment dosage) or ZDV, 3TC, and RAL administered from birth to age 6 weeks.d
Presumed Newborn HIV Exposure
  • Mothers with unknown HIV status who test HIV positive at delivery or postpartum or whose newborns have a positive HIV antibody test
ARV management as above (for higher risk of perinatal HIV transmission).

Infant ARVs should be discontinued immediately if supplemental testing confirms that the mother does not have HIV.
Newborn with HIVe
  • Positive newborn HIV virologic test/NAT
3-drug ARV regimen using treatment dosages
a See text for evidence supporting a 2-drug ARV prophylaxis regimen and empiric HIV therapy.
b See the Intrapartum Care section for guidance on indications for scheduled cesarean delivery and intrapartum IV ZDV to reduce the risk of perinatal HIV transmission for mothers with an elevated viral load at delivery.
c Most Panel members would opt to administer empiric HIV therapy to infants whose mothers had acute HIV during pregnancy because of the higher risk for in utero transmission. If acute HIV is diagnosed during breastfeeding, mother should stop breastfeeding.
d The optimal duration of empiric HIV therapy in newborns at higher risk of perinatal HIV transmission is unknown. Some Panel members opt to discontinue NVP, RAL, and/or 3TC when a birth NAT returns negative, while others would continue empiric HIV therapy for infants at highest risk of HIV acquisition for 6 weeks. In all cases, ZDV should be continued for 6 weeks. It is recommended that providers consult with an expert in pediatric HIV infection to determine therapy duration based on case-specific risk factors and interim HIV NAT results.
e Most Panel members do not recommend delaying the initiation of ART pending results of the confirmatory HIV NAT, given low likelihood of a false-positive HIV NAT.

Note: ARV drugs should be initiated as close to the time of birth as possible, preferably within 6 to 12 hours of delivery. See Table 12 for dosing specifics.

Key to Acronyms: 3TC = lamivudine; ART = antiretroviral therapy; ARV =antiretroviral; IV = intravenous; NAT = nucleic acid test; NVP = nevirapine; the Panel = Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission; RAL = raltegravir; ZDV = zidovudine

Table 12. Antiretroviral Dosing Recommendations for Newborns
Newborns at Low Risk of Perinatal HIV Transmission
Recommended Regimen Recommended Duration
  • ZDV
  • ZDV administered for 4 weeks
Newborns at Higher Risk of Perinatal HIV Transmission
Recommended Regimen Recommended Duration
  • 2-drug ARV prophylaxis with ZDV and 3 doses of NVP (NICHD-HPTN 040/PACTG 1043 regimen), or
  • ZDV administered for 6 weeks; 3 doses of NVP during the first week of life
  • Empiric HIV therapy with ZDV/3TC/NVP, or
  • ZDV administered for 6 weeks; 3TC and NVP administered for 2–6 weeks, up to 6 weeks of agea
  • Empiric HIV therapy with ZDV/3TC/RAL
  • ZDV administered for 6 weeks; 3TC and RAL administered for 2–6 weeks, up to 6 weeks of agea
Newborns with HIV Infection
Recommended Regimen Recommended Duration
  • HIV therapy with ZDV/3TC/NVP, or
  • Lifelong therapy
  • HIV therapy with ZDV/3TC/RAL
  • Lifelong therapy

Indication
Drug Low Risk Prophylaxis Higher Risk Prophylaxis: 2-Drug Higher Risk Prophylaxis:
Empiric and HIV Therapy
ZDV

Note: For newborns unable to tolerate oral agents, the IV dose is 75% of the oral dose while maintaining the same dosing interval.
≥35 Weeks Gestation at Birth:
  • ZDV 4 mg/kg/dose orally twice daily
Simplified Weight-Band Dosing for Newborns ≥35 Weeks Gestation at Birth:
Weight Band (kg) Volume (mL)
ZDV 10 mg/mL Oral Syrup Twice Daily
2 to <3 kg 1 mL
3 to <4 kg 1.5 mL
4 to <5 kg 2 mL
≥35 Weeks Gestation at Birth
Birth–4 Weeks:
  • ZDV 4 mg/kg/dose orally twice daily
Age >4 Weeks:
  • ZDV 12 mg/kg/dose orally twice daily
Simplified Weight-Band Dosing for Newborns Aged ≥35 Weeks Gestation from Birth to 4 Weeks:
Weight Band (kg) Volume (mL)
ZDV 10 mg/mL Oral Syrup Twice Daily
2 to <3 kg 1 mL
3 to <4 kg 1.5 mL
4 to <5 kg 2 mL
≥30 to <35 Weeks Gestation at Birth
Birth to Age 2 Weeks:
  • ZDV 2 mg/kg/dose orally twice daily
Age 2 Weeks to 4–6 Weeks:
  • ZDV 3 mg/kg/dose orally twice daily
≥30 to <35 Weeks Gestation at Birth
Birth to Age 2 Weeks:
  • ZDV 2 mg/kg/dose orally twice daily
Age 2 Weeks to 6–8 Weeks:
  • ZDV 3 mg/kg/dose orally twice daily
Age >6–8 Weeks:
  • ZDV 12 mg/kg/dose orally twice daily
<30 Weeks Gestation at Birth
Birth to Age 4–6 Weeks:
  • ZDV 2 mg/kg/dose orally twice daily
<30 Weeks Gestation at Birth
Birth to Age 4 Weeks:
  • ZDV 2 mg/kg/dose orally twice daily
Age 4 to 8–10 Weeks:
  • ZDV 3 mg/kg/dose orally twice daily
Aged >8–10 Weeks:
  • ZDV 12 mg/kg/dose orally twice daily
3TC N/A N/A ≥32 Weeks Gestation at Birth
Birth to Age 4 Weeks:
  • 3TC 2 mg/kg/dose orally twice daily
Age >4 Weeks:
  • 3TC 4 mg/kg/dose orally twice daily
NVP N/A ≥32 Weeks Gestation at Birth:
  • NVP in 3 doses given
  1. Within 48 hours of birth,
  2. 48 hours after the 1st dose, and
  3. 96 hours after the 2nd dose
Birth Weight 1.5 to 2 kg:
  • NVP 8 mg per dose orally. Note: No calculation is required for this dose; this is the actual dose, not a mg/kg dose.
Birth Weight >2 kg:
  • NVP 12 mg per dose orally. Note: No calculation is required for this dose; this is the actual dose, not a mg/kg dose.
≥37 Weeks Gestation at Birth
Birth to Age 4 Weeks:
  • NVP 6 mg/kg/dose orally twice dailyb
Age >4 Weeks:
  • NVP 200 mg/m2 of BSA/dose orally twice daily
34 to <37 Weeks Gestation at Birth
Birth to Age 1 Week:
  • NVP 4 mg/kg/dose orally twice daily
Age 1 to 4 Weeks:
  • NVP 6 mg/kg/dose orally twice daily
Age >4 Weeks:
  • NVP 200 mg/m2 of BSA/dose orally twice daily
Note: NVP dose adjustment at 4 weeks of age is optional for empiric HIV therapy.
RAL

Note: If the mother has taken RAL 2–24 hours prior to delivery, the neonate’s first dose of RAL should be delayed until 24–48 hours after birth; additional ARVs should be started as soon as possible.
N/A N/A ≥37 Weeks Gestation at Birth and Weighing ≥2 kgc
Birth to Age 6 Weeks:
Body Weight (kg) Volume (Dose) of Suspension, RAL 10 mg/mL, to be Administered
Birth to 1 Week: Once Daily Dosing Approximately 1.5 mg/kg/dose
2 to <3 kg 0.4 mL (4 mg) once daily
3 to <4 kg 0.5 mL (5 mg) once daily
4 to <5 kg 0.7 mL (7 mg) once daily
1 to 4 Weeks: Twice Daily Dosing Approximately 3 mg/kg/dose
2 to <3 kg 0.8 mL (8 mg) twice daily
3 to <4 kg 1 mL (10 mg) twice daily
4 to <5 kg 1.5 mL (15 mg) twice daily
4 to 6 Weeks: Twice Daily Dosing Approximately 6 mg/kg/dose
3 to <4 kg 2.5 mL (25 mg) twice daily
4 to <6 kg 3 mL (30 mg) twice daily
a The optimal duration of empiric HIV therapy in newborns at higher risk of perinatal HIV transmission is unknown. Some Panel members opt to discontinue NVP, RAL, and/or 3TC when birth NAT returns negative, while others would continue empiric HIV therapy for infants at the highest risk of HIV acquisition for 6 weeks. In all cases in which the newborn is at higher risk of HIV acquisition, ZDV should be continued for 6 weeks. Consultation with an expert in pediatric HIV to select a therapy duration based on case-specific risk factors and interim HIV NAT results is recommended.
b Investigational NVP treatment dose recommended by the Panel; FDA has not approved a dose of NVP for infants <1 month of age.
c RAL dosing is increased at 1 and 4 weeks of age because metabolism by UGT1A1 is low at birth and increases rapidly during the next 4 to 6 weeks of life. No dosing information is available for preterm or low birthweight infants.

Key to Acronyms: 3TC = lamivudine; ARV =antiretroviral; BSA = body surface area; FDA = Food and Drug Administration; IV = intravenous; N/A = no recommendation; NAT = nucleic acid test; NVP = nevirapine; the Panel = the Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission; RAL = raltegravir; UGT1A1 = uridine diphosphate glucotransferase; ZDV = zidovudine

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