Infant antiretroviral prophylaxis to prevent vertical HIV transmission in resource-rich settings

Risk of vertical transmission		Prophylactic regimen
Formula-fed newborns at low risk
Born at ≥37 weeks of gestation to a mother who: Did not have acute or primary HIV infection during pregnancy Has achieved and maintained viral suppression (at least two consecutive viral loads <50 copies/mL obtained at least four weeks apart) during pregnancy and delivery Is currently receiving and has received ≥10 weeks of ART during pregnancy Has no adherence concerns		Zidovudine administered for 2 weeks
Born to mothers who received antepartum ART with no adherence concerns, had viral level <50 copies/mL within 4 weeks of delivery, but do not meet the above criteria for two-week zidovudine regimen.		Zidovudine administered for 4 weeks
Breast-fed newborns at low risk
Born to mothers who received antepartum ART with no adherence concerns and had viral level <50 copies/mL at least throughout third trimester and at delivery.		Zidovudine administered for 6 weeks
Formula-fed newborns at high risk
Born to mothers who received antepartum ART but had one or more of the following: Adherence concerns Viral level ≥50 copies/mL near the time of delivery Unknown viral level near the time of delivery Born to mothers who did not receive antepartum ART Born to mothers with acute/primary* HIV infection during pregnancy Breastfed by mothers with acute/primary* HIV infection during breastfeeding^¶		Presumptive HIV therapy with zidovudine plus lamivudine plus either nevirapine or raltegravir for 6 weeks^Δ^◊
Drug	Gestational age at birth	Dosing^§
Zidovudine (ZDV)^¥	≥35 weeks	ZDV 4 mg/kg/dose orally twice daily Simplified weight-band dosing for newborns ≥35 weeks gestation at 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	Birth to age 2 weeks: ZDV 2 mg/kg/dose orally twice daily Age 2 weeks to 6 weeks: ZDV 3 mg/kg/dose orally twice daily
	<30 weeks	Birth to age 4 weeks: ZDV 2 mg/kg/dose orally twice daily Age 4 to 6 weeks: ZDV 3 mg/kg/dose orally twice daily
Abacavir (ABC)^‡	≥37 weeks	Birth to 1 month: ABC 2 mg/kg/dose orally twice daily Age 1 month to <3 months: ABC 4 mg/kg/dose orally twice daily
Lamivudine (3TC)	≥32 weeks	Birth to age 4 weeks: 3TC 2 mg/kg/dose orally twice daily Age >4 weeks: 3TC 4 mg/kg/dose orally twice daily
Nevirapine (NVP)^†	≥37 weeks	NVP 6 mg/kg/dose orally twice daily
	≥34 to <37 weeks	Birth to age 1 week: NVP 4 mg/kg/dose orally twice daily Age >1 week: NVP 6 mg/kg/dose orally twice daily
	≥32 to <34 weeks**	Birth to age 2 weeks: NVP 2 mg/kg/dose orally twice daily Age 2 to 4 weeks: NVP 4 mg/kg/dose orally twice daily Age 4 to 6 weeks: NVP 6 mg/kg/dose orally twice daily Age >6 weeks: NVP 200 mg/m² BSA per dose orally twice daily^¶¶
Raltegravir (RAL)^ΔΔ,^◊◊	≥37 weeks and weighing ≥2 kg	Body weight (kg)	Volume (dose) of RAL 10 mg/mL suspension
		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
		6 to <8 kg	4 mL (40 mg) twice daily

ART: antiretroviral therapy; NAAT: nucleic acid amplification test; IV: intravenous; BSA: body surface area; FDA: US Food and Drug Administration; UGT1A1: uridine diphosphate glucotransferase.

* Primary HIV infection refers to the first 6 months of infection.

¶ This statement only applies to individuals who are diagnosed with HIV while breastfeeding.

Δ The optimal duration of presumptive HIV therapy in newborns at high risk of vertical HIV transmission is unknown. We favor a 3-drug regimen for 6 weeks. An alternative approach to using a 3-drug regimen for the full 6-week duration, particularly if there are side effects or complications, is to discontinue the 3TC and NVP or RAL components after 2 weeks if the HIV NAAT at birth was negative and continue ZDV alone for the full 6 weeks. In highly select cases, a two-drug regimen might be appropriate. Consultation with an expert in pediatric HIV for regimen selection is recommended.

◊ Raltegravir (instead of nevirapine) should be used in infants at risk of HIV-2 infection.

§ These doses are only for the prophylaxis regimens in infants without confirmed HIV infection. Continuation of ART with potential regimen and/or dose adjustments is warranted for infants who are diagnosed with HIV infection.

¥ For newborns who are unable to tolerate oral agents, the IV dose is 75% of the oral dose while maintaining the same dosing interval.

‡ ABC is not approved by FDA for use in infants aged <3 months. Dosing recommendations have been modeled using pharmacokinetic simulation. Prior to using abacavir, negative testing for HLA-B5701 allele should be confirmed.

† Investigational NVP treatment dose recommended by the United States Department of Health and Human Services; the FDA has not approved a dose of NVP for infants <1 month of age.

** These doses may underestimate potential toxicity in infants in this age group as the doses are based on modeling and lower doses were used to develop the model than what is now recommended.

¶¶ Only make this dose increase for infants with confirmed HIV infection or in breastfed infants older than 6 weeks whose mother is found to have new onset viremia and 6-week presumptive therapy is initiated pending infant HIV status.

ΔΔ If the mother has taken RAL 2 to 24 hours prior to delivery, the neonate's first dose of RAL should be delayed until 24 to 48 hours after birth; ZDV and 3TC, however, should be started as soon as possible after birth. 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. If the two dose changes in the first month of life seem challenging for a family, an alternative is to increase to the 3 mg/kg twice daily dose upon discharge on day 4 or 5 of life.

◊◊ No dosing information for RAL is available for preterm or infants weighing <2 kg at birth.

Adapted from: Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States, HIV.gov 2023. Available at: clinicalinfo.hiv.gov/en/guidelines/perinatal/recommendations-arv-drugs-pregnancy-what-to-start-regimens-naive (Accessed on February 8, 2023).

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Infant antiretroviral prophylaxis to prevent vertical HIV transmission in resource-rich settings