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 HIV Infection

Last Updated: December 24, 2019; Last Reviewed: December 24, 2019

Panel's Recommendations for Antiretroviral Management of Newborns with Perinatal HIV Exposure or HIV Infection
Panel's Recommendations
  • All newborns who were perinatally exposed to HIV should receive postpartum antiretroviral (ARV) drugs to reduce the risk of perinatal transmission of HIV (AI).
  • Newborn ARV regimens administered at doses that are appropriate for the infant’s gestational age should be initiated as close to the time of birth as possible, preferably within 6 to 12 hours of delivery (AII).
  • A newborn’s ARV regimen should be determined based on maternal and infant factors that influence the risk of perinatal transmission of HIV (AII). 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 who are 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 it 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 doses (called antiretroviral therapy [ART]) to newborns with documented HIV infection (see Diagnosis of HIV Infection in Infants and Children).
  • A 4-week zidovudine (ZDV) ARV prophylaxis regimen can be used in newborns whose mothers received ART during pregnancy and had sustained viral suppression near delivery (defined as a confirmed HIV RNA level <50 copies/mL) and for whom there are no concerns related to maternal adherence (BII).
  • Newborns at higher risk of perinatal acquisition of HIV should initiate empiric HIV therapy or a multidrug ARV prophylaxis regimen (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 who did not achieve viral suppression near delivery (AII), or
    • Have primary or acute HIV infection during pregnancy (AII), or
    • Have primary or acute HIV infection while breastfeeding (AII).
  • Newborns of women with unknown HIV statuses who test HIV positive on expedited testing during labor or shortly after birth should initiate an ARV regimen (either empiric HIV therapy or multidrug ARV prophylaxis, based on clinician assessment of risk) (AII). If supplemental testing is negative, the ARV regimen should be discontinued (AII).
  • For newborns with HIV infection, ART should be initiated (AI).
  • The use of ARV drugs other than ZDV, lamivudine, and nevirapine cannot be recommended for any indication in premature newborns (<37 weeks gestational age) because of lack of dosing and safety data (BII).
  • 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. Neonatal 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 (1-888-448-8765).

Table 11. Newborn Antiretroviral Management According to Risk of HIV Infection in the Newborn
Level of Perinatal HIV Transmission Risk Description Neonatal ARV Management
Low Risk of Perinatal HIV Transmission

Mothers who received ART during pregnancy with sustained viral suppression (defined as a confirmed HIV RNA level <50 copies/mL) 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 loads near delivery, particularly when delivery was vaginal

Mothers with acute or primary HIV infection during pregnancy or breastfeeding (in which case, the mother should discontinue breastfeeding).c

Empiric HIV therapy using either ZDV, 3TC, and NVP (treatment dose) or ZDV, 3TC, and RAL administered from birth to age 6 weeks.d

or

Two-drug ARV prophylaxis (NICHD-HPTN 040/PACTG 1043 regimen) with 6 weeks ZDV and three doses of NVP (prophylactic doses, with doses given within 48 hours of birth, 48 hours after first dose, and 96 hours after second dose) 
Presumed Newborn HIV Exposure

Mothers with unconfirmed HIV status who have at least one positive HIV test at delivery or postpartum

or

Whose newborns have a positive HIV antibody test

ARV management as described above for newborns with a higher risk of perinatal HIV transmission

Infant ARV drugs should be discontinued immediately if supplemental testing confirms that the mother does not have HIV
Newborn with HIVe

Positive newborn HIV virologic test/NAT

Three-drug ARV regimen using treatment doses
a See text for evidence that supports the use of empiric HIV therapy and a two-drug ARV prophylaxis regimen.
b See Intrapartum Care 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, the mother should stop breastfeeding.
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 NAT performed shortly after birth returns negative, while others would continue empiric HIV therapy for infants at highest risk of HIV acquisition for 2 to 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 the 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: 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

Empiric HIV therapy with ZDV plus 3TC plus 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 plus 3TC plus RAL, or

ZDV administered for 6 weeks; 3TC and RAL administered for 2–6 weeks, up to 6 weeks of agea

Two-drug ARV prophylaxis with ZDV and three doses of NVP (NICHD-HPTN 040/PACTG 1043 regimen)

ZDV administered for 6 weeks; three doses of NVP during the first week of life

Newborns with HIV Infection
Recommended Regimen Recommended Durationb

HIV therapy with ZDV plus 3TC plus NVP, or

Lifelong therapy. NVP can be replaced with LPV/r when infant reaches a postmenstrual age ≥42 weeks and a postnatal age ≥14 days; NVP can be replaced with RAL at any age.

HIV therapy with ZDV plus 3TC plus RAL

Lifelong therapy


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

Note: For newborns who are 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 per dose orally twice daily
Simplified Weight-Band Dosing for Newborns Aged ≥35 Weeks Gestation at Birth
Weight Band  Volume of 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 to Age 4 Weeks:
  • ZDV 4 mg/kg per dose orally twice daily
Age >4 Weeks:
  • ZDV 12 mg/kg per dose orally twice daily
Simplified Weight-Band Dosing for Newborns Aged ≥35 Weeks Gestation from Birth to 4 Weeks
Weight Band Volume of 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 per dose orally twice daily
Age 2 Weeks to 4–6 Weeks:
  • ZDV 3 mg/kg per dose orally twice daily
≥30 to <35 Weeks Gestation at Birth
Birth to Age 2 Weeks:
  • ZDV 2 mg/kg per dose orally twice daily
Age 2 Weeks to 6–8 Weeks:
  • ZDV 3 mg/kg per dose orally twice daily
Age >6 to 8 Weeks:
  • ZDV 12 mg/kg per dose orally twice daily
<30 Weeks Gestation at Birth
Birth to Age 4–6 Weeks:
  • ZDV 2 mg/kg per dose orally twice daily
<30 Weeks Gestation at Birth
Birth to Age 4 Weeks:
  • ZDV 2 mg/kg per dose orally twice daily
Age 4 to 8–10 Weeks:
  • ZDV 3 mg/kg per dose orally twice daily
Aged >8 to 10 Weeks:
  • ZDV 12 mg/kg per dose orally twice daily
3TC NRS NRS ≥32 Weeks Gestation at Birth
Birth to Age 4 Weeks:
  • 3TC 2 mg/kg per dose orally twice daily
Age >4 Weeks:
  • 3TC 4 mg/kg per dose orally twice daily
NVP NRS ≥32 Weeks Gestation at Birth:
  • NVP in three doses, given within 48 hours of birth, 48 hours after the first dose, and 96 hours after the second dose
Birth Weight 1.5 to 2 kg:
  • NVP 8 mg per dose orally. 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. 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 per dose orally twice dailyc
Age >4 Weeks:
  • NVP 200 mg/m2 of BSA per dose orally twice daily
34 to <37 Weeks Gestation at Birth
Birth to Age 1 Week:
  • NVP 4 mg/kg per dose orally twice daily
Age 1 to 4 Weeks:
  • NVP 6 mg/kg per dose orally twice daily
Age >4 Weeks:
  • NVP 200 mg/m2 of BSA per 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 ARV drugs should be started as soon as possible.7
NRS NRS ≥37 Weeks Gestation at Birth and Weighing ≥2 kgd
Birth to Age 6 Weeks
Body Weight  Volume (Dose) of RAL 10 mg/mL Suspension
Birth to 1 Week: Once Daily Dosing Approximately 1.5 mg/kg per 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 per 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 per dose
3 to <4 kg 2.5 mL (25 mg) twice daily
4 to <6 kg 3 mL (30 mg) twice daily
6 to <8 kg 4 mL (40 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 2–6 weeks. In all cases in which the newborn is at higher risk of HIV acquisition, ZDV should be continued for 6 weeks. In all cases in which the newborn is at higher risk of HIV acquisition, ZDV should be continued for 6 weeks. Consulting an expert in pediatric HIV is recommended when selecting a therapy duration based on case-specific risk factors and interim HIV NAT results.
For ARV management after the newborn period, see the Pediatric Antiretroviral Guidelines.
c This dose is an investigational NVP treatment dose recommended by the Panel; the FDA has not approved a dose of NVP for infants aged <1 month.
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 4–6 weeks of life. No dosing information is available for preterm infants or infants weighing <2 kg at birth.

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

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