Version July 2025
INTRODUCTION —
Advances in the potency and tolerability of antiretroviral (ARV) drugs have resulted in high rates of viral suppression in pregnant women living with human immunodeficiency virus (HIV) and considerable progress towards the elimination of new infections in infants. In addition to maternal antiretroviral therapy (ART), the use of ARVs as prophylaxis in infants with exposure to HIV continues to play a key role in preventing new infections.
We recognize that not all pregnant, postpartum, and lactating individuals identify as women or mothers. The topics discussed here are based on risks driven by pregnancy and transmission of infection to the fetus/infant and apply regardless of the pregnant person's gender identity. For simplicity, we use the term "woman" to signify the pregnant person or someone who may become pregnant and the term "mother" to signify the birthing biological parent of a child (regardless of gender identity and/or parental rights).
This topic will review the management of infants born to women with HIV, including the use of ARV drugs as prophylaxis and additional screening. Management of this patient population in resource-limited settings is discussed separately. (See "Prevention of vertical HIV transmission in resource-limited settings", section on 'Infant postnatal prophylaxis' and "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Infant antiretroviral use'.)
Approach to the diagnosis of HIV in infants and children younger than 18 months is discussed separately as well. (See "Pediatric HIV infection: Diagnostic testing in children younger than 18 months".)
Management of the mother during pregnancy, labor, and postpartum is discussed in the following topics:
●Resource-abundant settings:
•(See "Prenatal evaluation of women with HIV in resource-abundant settings".)
•(See "Intrapartum and postpartum management of pregnant women with HIV in resource-abundant settings".)
●Resource-limited settings:
•(See "Prevention of vertical HIV transmission in resource-limited settings".)
•(See "Prevention of HIV transmission during breastfeeding in resource-limited settings".)
GENERAL PRINCIPLES
Risk of perinatal HIV acquisition — Infants can acquire HIV from exposure in utero, during delivery, or during breastfeeding [1]. The risk of HIV acquisition from exposure is driven by whether or not the mother is receiving antiretroviral therapy (ART) and the level of maternal viremia [2-4]. (See "Prevention of vertical HIV transmission in resource-limited settings", section on 'Epidemiology' and "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Epidemiology of HIV transmission through breastfeeding'.)
Prompt initiation of prophylaxis for HIV-exposed infants — We administer antiretroviral (ARV) prophylaxis to all infants born to women with HIV to decrease the risk of HIV acquisition. Infant ARV prophylaxis should be initiated as soon as possible after birth, ideally within the first 6 to 12 hours of delivery [5,6]. Blood for HIV testing should be drawn before or immediately after initiating an ARV drug regimen. An exception is infants at very low risk of acquiring HIV who are not being breastfed, for whom testing can be delayed until two weeks of life. (See "Pediatric HIV infection: Diagnostic testing in children younger than 18 months", section on 'Approach to perinatal HIV diagnosis'.)
APPROACH TO ARV DRUG MANAGEMENT —
The choice and duration of antiretroviral (ARV) prophylaxis in HIV-exposed infants is based on the timing and level of HIV viremia in the mother and choice of infant feeding modality (table 1 and algorithm 1).
Clinicians managing these patients should also consider consulting a pediatric HIV expert, the US NIH DHHS Guidelines, or the Perinatal HIV/AIDS consultation line (888-448-8765) at the UCSF National Clinician Consultation Center for additional guidance.
Infant prophylaxis regimens in resource-limited settings are discussed separately. (See "Prevention of vertical HIV transmission in resource-limited settings", section on 'Infant postnatal prophylaxis' and "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Infant antiretroviral use'.)
Initial ARV prophylaxis for all HIV-exposed infants
Infants born to mothers with sustained viral suppression since 20 weeks gestation — Infants born to mothers with sustained viral suppression since 20 weeks gestation are at very low risk of acquiring HIV during birth.
●Clinical approach – For infants born to women who have maintained a viral load <50 copies/mL on antiretroviral therapy (ART) from 20 weeks gestation through delivery (based on clinical judgement but ideally via documented HIV ribonucleic acid [RNA] levels), we suggest two weeks of infant prophylaxis with zidovudine (twice daily) (table 1 and algorithm 1 and table 2) [5]. This suggestion is in line with the recommendations outlined in the United States Department of Health and Human Services (DHHS) perinatal HIV guidelines. There is some variability in guidance from other countries; most recommend two to four weeks of zidovudine, although a small number of national guidelines support giving no prophylaxis in low risk scenarios [7].
When using highly sensitive viral assays, some women may have detectable and/or quantifiable viral loads of <50 copies/mL during pregnancy. While these low levels could prompt more frequent monitoring, most experts do not consider these levels to confer significant HIV transmission risk to merit additional prophylaxis for the infant.
●Rationale
•Risk of vertical transmission in this patient group – The risk of perinatal HIV transmission in the setting of sustained maternal viral suppression during pregnancy is very low [8,9]. In a nationwide prospective multicenter French cohort that included over 6000 women with HIV who were on ART at conception, perinatal transmission rate was 0.03 percent from 2011 to 2017; there were no infections among 5482 infants born to women on ART at conception who had undetectable viral load (<50 copies/mL) near delivery, whereas transmission was 1.1 percent for women on ART at conception but who had a detectable viral load near delivery [8]. The United States DHHS guidelines chose a cutoff of 20 weeks gestation for determining choice of ARV prophylaxis because the risk of in utero transmission in the first and early second trimester appears to be very low [1].
•Duration of prophylaxis – Duration of zidovudine prophylaxis is largely based on expert opinion since there are limited data available evaluating the optimal duration of zidovudine prophylaxis in this low-risk infant group. At the beginning of the HIV pandemic, six weeks of zidovudine was the standard practice [10]. However, since the risk of in utero or peripartum transmission to infants born to mothers who have been receiving ART and maintaining virologic suppression throughout their pregnancy have decreased to near zero [8], there has been a desire to utilize shorter durations of zidovudine to avert unnecessary toxicity, such as anemia [11,12]. So far, there has been no evidence of increased transmission risk with the use of shorter durations.
•Preferred antiviral drugs – Zidovudine (twice daily) has been the drug of choice for infant HIV prophylaxis since 1994 when the seminal 076 trial demonstrated the efficacy of combining maternal zidovudine during pregnancy and intrapartum with a six-week course of infant zidovudine prophylaxis in preventing perinatal HIV transmission [10]. Zidovudine also has the largest body of evidence on efficacy and safety in infants compared to other ARVs.
Infants born to mothers without sustained viral suppression after 20 weeks gestation — For infants born to mothers who had detectable viral loads after 20 weeks of gestation, the approach to prophylaxis depends on the mother's viral load in the month prior to delivery.
Detectable viral load within four weeks prior to delivery — For infants born to women who have viremia (HIV RNA level ≥50 copies/mL, either documented or presumed if mother was not on treatment or non-adherent to ART) at the time of, or in the four weeks prior to delivery, we recommend a three-drug ARV infant regimen for "presumptive therapy." Duration of presumptive therapy ranges from two to six weeks. If the duration of the three-drug regimen is shorter than six weeks, zidovudine should be continued alone, to complete a total of six weeks of prophylaxis.
●Preferred three-drug regimens – We administer infant antiretroviral prophylaxis with a three-drug regimen (zidovudine, lamivudine, plus either treatment-dose nevirapine or raltegravir (table 1 and table 2 and algorithm 1)). We generally prefer treatment with nevirapine-based regimens, supported by evidence from randomized clinical trials of nevirapine infant prophylaxis during breastfeeding and years of clinical experience with nevirapine as both prophylaxis and treatment. Raltegravir is more complicated than nevirapine to administer, requiring dose and frequency changes over the first few weeks of life. However, raltegravir should be used when there is concern for infant exposure to HIV-2 virus or to nevirapine-resistant virus (based on maternal viral genotype testing results or history of clinical failure while taking non-nucleoside reverse transcriptase inhibitor [NNRTI]-based ART in the mother).
Decisions about infant prophylaxis regimens for high-risk infants should generally be made in consultation with a pediatric HIV specialist, preferably before delivery, and should consider the balance between the transmission risk and potential neonatal toxicities for the individual infant, with parental counseling on these issues.
●Duration – We suggest a duration of two weeks of the three-drug regimen, followed by four weeks of zidovudine alone to minimize adverse drug effects in the infant [5]. However, some experts prefer to continue with the three-drug regimen for the full six weeks if the infant is tolerating the regimen. The choice of a longer duration of the three-drug regimen (ie, three to six weeks) could be utilized for infants exposed to high levels of virus, weighing potential benefit against unknown but presumably greater risk of adverse effects. If a transition from three drugs to prophylaxis with zidovudine alone is chosen to complete the 6-week prophylaxis period, at least one HIV nucleic acid test (ideally obtained at birth) should be negative before the switch, to exclude the possibility of established infection in the infant. (See "Pediatric HIV infection: Diagnostic testing in children younger than 18 months", section on 'Mother with HIV'.)
●Rationale – In a nonbreastfeeding setting, most perinatal infections are related to HIV exposure in the four weeks prior to and during delivery, so viremia in that period confers the highest risk of HIV acquisition.
•Rationale for a three-drug regimen – The rationale for using a three-drug regimen is twofold: 1) it serves as "presumptive treatment" for infants who may be born having already been infected in utero and 2) it serves as multidrug prophylaxis for infants with high-risk HIV exposure.
-Nevirapine-based three-drug regimens – The HIV Prevention Trials Network (HPTN) 040/Pediatric AIDS Clinical Trial Group 1043 study is the only randomized trial evaluating the efficacy of a three-drug combination prophylaxis regimen in preventing intrapartum vertical HIV transmission among infants born to women who presented late to care and received either intrapartum zidovudine only or no antiretroviral agents at all [13]. The rate of intrapartum transmission of HIV was higher when infants received six weeks of zidovudine alone (4.8 percent) compared with six weeks of zidovudine plus three prophylaxis-level doses of nevirapine (the first within 48 hours of birth, the second 48 hours after the first dose, and the third 96 hours after the second dose; 2.2 percent) or six weeks of zidovudine plus two weeks of nelfinavir and lamivudine (2.4 percent). However, neutropenia was more common with the triple-drug regimen than the other two regimens. Thus, the two-drug zidovudine plus nevirapine regimen offered the most favorable balance between efficacy and side effects. However, it is hypothesized that replacing nelfinavir in the three-drug regimen with treatment-dose nevirapine or raltegravir (which have greater potency against HIV) and giving the regimen for a full six weeks would result in even greater preventive efficacy that would offset the potential toxicity of a three-drug regimen. Observational data suggest that the three-drug regimen of zidovudine, lamivudine, and nevirapine is associated with slightly lower hemoglobin levels and higher premature discontinuation rates but no major toxicity compared with zidovudine only [14].
Clinical trials evaluating the impact of very early treatment on viral reservoirs in infants with HIV by treating high-risk HIV-exposed infants with the three-drug regimen of zidovudine, lamivudine, and nevirapine at treatment doses will inform the pharmacokinetics and safety of this regimen in infants. The IMPAACT P1115 study found that nevirapine dosed at 6 mg/kg twice daily for term infants, or 4 mg/kg twice daily followed by 6 mg/kg twice daily afterward for preterm infants (34 to <37 weeks gestational age), was safe and provided therapeutic exposure nevirapine concentrations [15]. Preliminary findings from P1115 have also shown that early ART for infants with in-utero HIV-1 infection achieved sustained virological suppression as well as restricted HIV-1 reservoirs by two years of age [16].
-Raltegravir-based three-drug regimens – Raltegravir is an alternative to nevirapine and may be a more potent option for "presumptive therapy" as infant prophylaxis than a nevirapine-based triple-drug regimen. In trials performed in adults with HIV, raltegravir was associated with greater and more durable viral suppression and less toxicity than efavirenz, another NNRTI similar to nevirapine [17]. Raltegravir is available in a formulation appropriate for neonates and has defined neonatal dosing. However, in the absence of substantial neonatal safety data for raltegravir and the abundant neonatal safety data of nevirapine [15], we continue to prefer nevirapine-based three-drug regimens for now. The three-drug regimen of zidovudine, lamivudine, and raltegravir is under study in some trials [18,19]. Data from these studies will guide future recommendations.
•Duration – The rationale for a two week duration of the three-drug regimen followed by four weeks of zidovudine comes from the HPTN 040/Pediatric AIDS Clinical Trial Group 1043 trial that is discussed above [13]. Although some experts would give the three-drug regimen for the full six weeks, we prefer a two-week duration of the three-drug regimen followed by four weeks of zidovudine alone because the results of HIV nucleic acid birth testing should generally be available by two weeks, excluding the possibility that the infant was born already having been infected in utero, which is the main reason for initially administering a three-drug "presumptive treatment" regimen.
Undetectable viral load in the four weeks prior to delivery — For infants whose mothers experienced viremia during gestation but maintain an undetectable viral load during the four weeks prior to delivery, there is no consensus on infant ARV management (table 1 and algorithm 1). Some pediatric HIV experts favor administering the three-drug presumptive treatment regimen for six weeks, while others prefer to administer two to six weeks of zidovudine monotherapy. We thus favor a process of shared decision-making between providers and parents, weighing the concerns about risk of infection against the desire to avoid side effects from ARVs. The higher the maternal viral load (and the closer in timing it is to delivery), the higher the risk of transmitting HIV in utero to the infant [2,20,21]. For example, in a woman who likely acquired HIV during pregnancy (suggesting very high viral loads), the risk of in utero transmission to the fetus is high and a three-drug regimen is likely beneficial. In contrast, in a woman who experienced transient viremia due to poor ART adherence early during her pregnancy, in utero transmission may still be unlikely and administering two to six weeks of zidovudine monotherapy to avoid side effects in the newborn may be reasonable.
The primary reason to administer a three-drug presumptive treatment regimen is to provide potential early treatment if the infant acquired HIV in utero. However, the potential benefit of early treatment starting at birth of infants specifically infected in utero is unclear, since these infants will likely be rapidly diagnosed in the first two weeks of life via HIV nucleic acid testing at birth. Precise estimates of the risk of in utero infection at different time points during gestation are not available but the overall rates of in utero infection are likely low. An early modeling study estimated 3 percent of transmissions occurred before 14 weeks' gestation, 17 percent from 14 to 36 weeks, 50 percent from 36 weeks through labor, and 30 percent from intrapartum exposure [1]. However, this was before widespread use of effective ART. There are case reports of HIV being identified in fetal tissue ≤20-weeks' gestation, but whether or not they represented established infection remains unclear [22,23]. Definitive diagnosis of in utero infection during pregnancy would require invasive sampling, conferring risk that is not ethically or medically indicated.
Details on infant prophylaxis with zidovudine monotherapy are discussed separately.
Details on three-drug presumptive treatment regimens are also discussed separately.
Continuation of ARV prophylaxis for breastfed infants — The initial ART prophylaxis regimen in breastfed infants mirrors that of the formula-fed infants. (See 'Initial ARV prophylaxis for all HIV-exposed infants' above.)
However, breastfed infants continue to have ongoing exposure to HIV through breastmilk beyond delivery. Continuation of ARV prophylaxis following the initial infant prophylaxis regimen in breast-fed infants is based on assessment of current and anticipated virologic status of the breastfeeding mother. Given that risk can change over time, plans for infant prophylaxis during breastfeeding are ideally made during the antepartum period and reassessed at the time of delivery and regularly during the breastfeeding period.
Clinicians in the United States may consult the National Perinatal HIV Hotline (1-888-448-8765) if they have questions regarding patients with HIV who desire to breastfeed [5]. Additional information can be found in the US NIH DHHS Guidelines.
We continue to monitor breastfed infants for HIV acquisition with HIV testing every three months during breastfeeding as well as four to six weeks, three months, and six months after cessation of breastfeeding (see "Pediatric HIV infection: Diagnostic testing in children younger than 18 months", section on 'Breastfed infants'). If an infant is diagnosed with HIV, the infant should be promptly transitioned to a full antiretroviral regimen and HIV drug resistance testing should be sent.
Clinical decisions about maternal ART, viral load monitoring, and counseling of the mother in relation to breastfeeding are discussed separately. (See "Intrapartum and postpartum management of pregnant women with HIV in resource-abundant settings", section on 'Breastfeeding'.)
●Infants of breastfeeding mothers who have sustained viral suppression on ART
•Clinical approach – For decisions about prophylaxis for infants of women who have demonstrated sustained viral suppression on ART, we engage in shared decision-making with the mother.
If the mother has a long history of virologic suppression and is confident about adherence postpartum, we support providing no additional prophylaxis to infants beyond what is being used in the peripartum period (eg, two weeks of zidovudine in most cases). (See 'Infants born to mothers with sustained viral suppression since 20 weeks gestation' above.)
However, new barriers to adherence often arise for postpartum women, and some clinicians or mothers may anticipate concerns with being able to maintain virologic suppression. In these scenarios, once daily nevirapine or twice daily lamivudine (table 3) can be administered after completing the initial prophylaxis regimen as a "safety net" in case viremia occurs in the mother.
Guidance on the use of ARV prophylaxis for low-risk infants during breastfeeding varies. The United States DHHS guidelines panel could not reach a consensus on a recommendation; most panel members do not extend prophylaxis beyond the initial two weeks of zidovudine recommended for all infants of mothers with viral suppression while others extend this initial prophylaxis regimen to complete four or six weeks of initial prophylaxis (table 2) or continue prophylaxis after the initial regimen for the duration of breastfeeding (table 3) [5]. The World Health Organization (WHO) recommends six weeks of nevirapine from birth for low risk infants [24] while the British HIV Association (BHIVA) recommends no extension of prophylaxis past the two weeks of zidovudine recommended for low risk infants [5,25].
For infants who receive extended prophylaxis during breastfeeding, we suggest assessing blood counts and liver function testing once in the first four to eight weeks of life, and thereafter if clinically indicated.
•Rationale – The benefit of continuing infant ART prophylaxis for the duration of breastfeeding when the mother is virally suppressed is unclear. In a double-blinded, randomized trial in sub-Saharan Africa that included a subset of 413 breastfed infants whose mothers were on ART at the onset of breastfeeding, there was no difference in rates of HIV diagnosis at six months in the infants among those who continued daily nevirapine prophylaxis for six months versus those who stopped prophylaxis at six weeks (0.5 versus 0 percent) [26]. In the open-label IMPAACT PROMISE trial that randomized 2431 mother-infant pairs to either infant prophylaxis (without maternal ART) or maternal ART only (without infant prophylaxis), 10 of 1211 (0.8 percent) infants receiving nevirapine in the infant prophylaxis arm acquired HIV infection, compared to 8 of 1218 (0.7 percent) in the maternal treatment arm [27].
However, cases of transmission have been documented when mothers have had transient viremia [4,27-41]. ARV prophylaxis for the breastfed infant appears to be very effective in preventing transmission when there are unanticipated lapses in adherence or other circumstances that lead to maternal viremia [26,27].
Frequent viral load testing in breastfeeding women can be an effective approach in women who prefer to minimize their infants' exposure to ARV drugs. In the open-label, randomized PROMISE-EPI trial that evaluated the strategy of same day initiation of infant ARV prophylaxis with twice daily lamivudine when women were identified to have a VL >1000 copies/mL during breastfeeding (tested at approximately 6.4 weeks and approximately six months postpartum), only 1 of 622 infants randomized to the intervention arm became infected (and that infant had not received lamivudine for five months prior to diagnosis) [42]. (See "Intrapartum and postpartum management of pregnant women with HIV in resource-abundant settings", section on 'Breastfeeding'.)
Our recommendation for assessing blood counts and liver function in the infants once at baseline is to assess for early toxicity and to provide a baseline with which to compare subsequent testing results, if indicated. There is no consensus about how to approach monitoring for toxicity during extended prophylaxis for breastfed infants. Neither the United States National Institute of Health Department of Health and Human Services (NIH DHHS) guidelines nor the American Academy of Pediatrics (AAP) guidelines provide specific guidance [43], but both groups endorse the safety of once daily nevirapine and twice daily lamivudine. There have been no studies examining the optimal way to monitor for toxicity. The safety of once daily nevirapine was evaluated in IMPAACT 1077BF, the breastfeeding component of the PROMISE trial [27]. Among 1204 infants who started once daily nevirapine in the infant prophylaxis arm, there were no cases of hypersensitivity reported and no differences in grade 3 or 4 adverse events rates or liver or skin toxicity between the two study arms; 20 infants (2 percent) stopped prophylaxis because of concerns for toxicity. In the randomized PROMISE-EPI trial that consisted of over 1500 infants randomized to receiving twice daily lamivudine starting at six weeks for six months during breastfeeding or placebo, there was no difference in adverse event rates between the two arms (65 [55 percent] events in 62 [8 percent] infants in the intervention group compared with 54 [45 percent] events in 53 [7 percent] infants in the control group) [42]. Four severe adverse events occurred while infants were taking lamivudine, with only one considered possibly related to the study drug (anemia).
●Infants of breastfeeding mothers who are not virally suppressed on ART
•Clinical approach – For infants of mothers who are not virally suppressed on ART, we do not advise breastfeeding given the high risk of HIV transmission. For those who still choose to breastfeed, we administer antiviral prophylaxis for the infant. We favor six weeks of three-drug presumptive HIV therapy (table 1 and table 2) followed by once daily nevirapine prophylaxis for the infant until six weeks after weaning (table 3). If the mother has nevirapine-resistant virus or the infant does not tolerate nevirapine, lamivudine is an alternative.
•Rationale – Antiretroviral drug prophylaxis in infants breastfed by mothers who are not on ART has been shown to reduce the risk of postnatal transmission in resource-limited settings. In a double-blinded, randomized trial in sub-Saharan Africa in 982 infants breastfed by mothers not on ART, the rate of HIV infection at six months was lower in infants who continued daily nevirapine prophylaxis for six months compared with those who stopped prophylaxis at six weeks (1.3 versus 3.4 percent) [26].
Infants born to mothers with unknown HIV status — For the infant whose mother's HIV status is unknown postpartum (including individuals at risk for HIV infection who were not retested in the third trimester), rapid HIV testing of the mother and/or infant with a combination antigen-antibody assay is recommended as soon as possible. The results of serologic testing (mother or infant) reflect the HIV status of the mother, not the infant, since it is maternal antibodies to HIV that will be detected.
If the initial test is positive, administer infant combination antiretroviral prophylaxis as given for high-risk infants while awaiting confirmatory HIV testing (table 1 and table 2) [5]. (See 'Detectable viral load within four weeks prior to delivery' above.)
For mothers who were planning to breastfeed, breastmilk should be expressed and stored appropriately until all HIV test results are reviewed. If testing confirms that the mother does not have HIV, the mother can initiate breastfeeding without precautions and the infant’s prophylaxis regimen can be discontinued. (See "Screening and diagnostic testing for HIV infection in adults".)
NEONATAL DRUG SAFETY AND PHARMACOLOGY —
It is important to note that pharmacokinetic data to allow appropriate dosing recommendations in neonates are only available for zidovudine, lamivudine, abacavir, nevirapine, and raltegravir, and in preterm infants, only for zidovudine, lamivudine, and nevirapine. Furthermore, most of the available pharmacokinetic data for nevirapine are for lower prophylaxis doses as opposed to treatment-level dosing, and the desired trough levels for the two doses are different (the target trough level for prophylaxis is <100 ng/mL whereas trough level for treatment is 3000 ng/mL).
Observational data on the use of three-drug prophylaxis regimens among 143 neonates (21 percent of whom were <37 weeks gestation and 40 percent of whom received zidovudine, lamivudine, and treatment-dose nevirapine as their regimen) demonstrated higher rates of nonspecific adverse signs and symptoms (10 percent) as well as premature drug discontinuation (10 percent) with three drugs compared with zidovudine alone (0 and 2 percent, respectively), but have not suggested major toxicity [14].
A multicenter trial of full-term neonates exposed to HIV found daily raltegravir safe and well tolerated during the first six weeks of life [44]. There were no clinical adverse reactions. Despite initial concerns that raltegravir-albumin binding might displace bilirubin bound to albumin in neonates resulting in hyperbilirubinemia, studies have shown raltegravir has minimal effect on bilirubin-albumin binding at the typical peak concentrations reached with usual dosing [45]; in the trial, there were only two cases of mild nonserious bilirubin elevations in newborns receiving raltegravir.
OTHER POSTNATAL MANAGEMENT CONSIDERATIONS —
Infants born to mothers with HIV require other management considerations besides initiation of ART in addition to the typical newborn screening that is performed in the general population. (See "Overview of newborn screening".)
Congenital CMV testing — We test for congenital cytomegalovirus (CMV) in all infants born to mothers with HIV. We conduct testing within the first 21 days of an infant's life with a urine and/or saliva polymerase chain reaction (PCR) assay [5]. Among CMV-seropositive women, the rate of CMV shedding from the cervix is higher in women with HIV compared with women without HIV and neonates born to mothers with HIV are more likely to have congenital CMV infection, especially if the neonate is infected with HIV [46-49]. We test all infants for congenital CMV since congenital CMV is best diagnosed before the 21st day of life, when the HIV status of the neonate may not yet be known. Management of congenital CMV is discussed elsewhere. (See "Congenital cytomegalovirus (cCMV) infection: Clinical features and diagnosis", section on 'Newborn screening for congenital cytomegalovirus' and "Congenital cytomegalovirus (cCMV) infection: Management and outcome", section on 'Antiviral treatment'.)
Testing in infants born to mothers coinfected with HBV and/or HCV
●For infants born to mothers with a positive hepatitis B surface antigen (HBsAg), we administer hepatitis B immune globulin and the first dose of the hepatitis B virus (HBV) vaccine series as soon as possible and preferably within 12 hours after birth [5]. Further discussion of immune globulin and vaccine administration and management of perinatal HBV transmission is discussed elsewhere. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Routine infant immunization' and "Hepatitis viruses and the newborn: Clinical manifestations and treatment", section on 'Hepatitis B'.)
●For infants born to mothers with known or suspected HCV, we send a hepatitis C virus (HCV) RNA test at two to six months of age to evaluate for perinatal HCV transmission [5]. Details of diagnosis and management of HCV in young children is discussed elsewhere. (See "Vertical transmission of hepatitis C virus", section on 'Diagnosis' and "Hepatitis viruses and the newborn: Clinical manifestations and treatment", section on 'Hepatitis C'.)
Limited role for pneumocystis prophylaxis — Although the United States Department of Health and Human Services (DHHS) guidelines suggest Pneumocystis jirovecii pneumonia (PJP) prophylaxis in select infants starting at the age of two months, in reality, most infants exposed to HIV in resource-abundant settings do not meet the indications criteria for PJP prophylaxis [5]. Most HIV-exposed infants do not require prophylaxis because they are either low risk for HIV acquisition and/or HIV infection can be presumptively excluded by two months of age. Despite Pneumocystis jirovecii being ubiquitous in the environment, acquisition of PJP within the first four weeks of life is rare. Most breastfed infants are also very low risk for acquiring HIV (as breastfeeding is only recommended for mothers with suppressed viral loads) and thus do not require prophylaxis.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: HIV infection in infants and children".)
SUMMARY AND RECOMMENDATIONS
●Risk of perinatal HIV acquisition – Infants can acquire HIV in utero, during delivery, or during breastfeeding. The risk from exposure is driven by whether or not the mother is receiving antiretroviral therapy (ART) and the level of maternal viremia. (See 'Risk of perinatal HIV acquisition' above and "Prevention of vertical HIV transmission in resource-limited settings", section on 'Mechanisms of transmission'.)
●Prompt initiation of antiretroviral drugs for exposed infants – Infant antiretroviral (ARV) prophylaxis should be initiated as soon as possible after birth, ideally within the first 6 to 12 hours of delivery. (See 'Prompt initiation of prophylaxis for HIV-exposed infants' above.)
●Initial ARV prophylaxis for all HIV-exposed infants
•Infants born to mothers with sustained viral suppression after 20 weeks gestation – For infants born to women who have maintained a viral load <50 copies/mL on ART from 20 weeks gestation through delivery (based on clinical judgement but ideally via documented HIV RNA levels), we suggest two weeks of prophylaxis with zidovudine (table 1 and table 2 and algorithm 1) (Grade 2C). Other experts choose to administer four weeks of zidovudine, and a small number support giving no prophylaxis in very low risk scenarios. (See 'Infants born to mothers with sustained viral suppression since 20 weeks gestation' above.)
•Infants born to mothers without sustained viral suppression after 20 weeks gestation
-For infants born to mothers who have viremia (HIV RNA level ≥50 copies/mL, either documented or presumed if mother was not on treatment or non-adherent to ART) at the time of, or in the four weeks prior to delivery, we recommend presumptive therapy with a three-drug antiretroviral regimen (table 1 and table 2 and algorithm 1) (Grade 1B). We suggest a two week duration of the three-drug regimen, followed by four weeks of zidovudine alone to minimize adverse drug effects in the infant (Grade 2C). However, longer durations of the three-drug regimen (eg, three to six weeks) may be utilized for infants exposed to high levels of virus or those in whom HIV nucleic acid testing at birth was not performed, weighing potential benefit of presumptive therapy against unknown but presumably greater risk of adverse effects with three-drug regimens. (See 'Detectable viral load within four weeks prior to delivery' above.)
-For infants whose mothers experienced viremia during gestation but maintained an undetectable viral load during the four weeks prior to delivery, we engage in shared decision making with the parents regarding whether to administer presumptive antiretroviral therapy with a three-drug regimen or to administer zidovudine alone for two to six weeks (table 1 and table 2 and algorithm 1).
The concerns about risk of infection in the infant must be weighed against the desire to avoid side effects from ARVs. The higher the maternal viral load (and the closer in timing it is to delivery), the higher the risk of transmitting HIV in utero to the infant. (See 'Undetectable viral load in the four weeks prior to delivery' above.)
●Continuation of ARV prophylaxis for breastfed infants
•Infants of breastfeeding mothers who have sustained viral suppression – For these infants, we engage in shared decision-making with the breastfeeding mother. If the mother is confident in her adherence to ART in the post-partum period, we prefer not to extend prophylaxis beyond the two-week zidovudine prophylaxis that is recommended for low-risk infants. However, some experts would extend the initial single-drug prophylaxis regimen to four or six weeks. If the mother has concern for maintaining adherence to ART while breastfeeding, once daily nevirapine prophylaxis for the infant for the duration of breastfeeding is preferred (table 3). (See 'Continuation of ARV prophylaxis for breastfed infants' above.)
•Infants of breastfeeding mothers without sustained viral suppression – For these infants, we do not advise breastfeeding as the risk of transmission of HIV to the infant through breastmilk is high. (See 'Continuation of ARV prophylaxis for breastfed infants' above.)
●Newborn CMV testing in all HIV-exposed infants – We test all infants born to mothers with HIV for congenital CMV with a urine and/or saliva PCR assay within the first 21 days of life. (See "Congenital cytomegalovirus (cCMV) infection: Clinical features and diagnosis", section on 'Newborn screening for congenital cytomegalovirus'.)
