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Intrapartum and postpartum management of pregnant women with HIV and infant prophylaxis in resource-rich settings

Intrapartum and postpartum management of pregnant women with HIV and infant prophylaxis in resource-rich settings
Literature review current through: Aug 2023.
This topic last updated: Feb 27, 2023.

INTRODUCTION — The management of the pregnant woman with human immunodeficiency virus (HIV) infection has evolved significantly over the past 29 years in light of advancements in drug development and a greater understanding of the prevention of vertical HIV transmission. In the United States and Europe, the risk of HIV transmission from mother to infant has declined to historically low levels with the use of antiretroviral medications [1-3]. Contributions to this successful prevention effort include universal testing of pregnant women for HIV infection, antiretroviral therapy (ART) for all pregnant women with HIV, and the use of cesarean delivery in certain circumstances. (See "Prenatal evaluation of women with HIV in resource-rich settings".)

We recognize that not all pregnant, postpartum, and lactating individuals identify as women or mothers. Using gender-inclusive language, however, is not possible in all languages and all countries and for all our readers. The topics discussed here are based on risks driven by biological sex and not gender identity. Therefore, throughout this topic, we use the term “woman” to signify a person of the female sex (regardless of gender identity) and the term “mother” to signify the female biological parent of a child (regardless of gender identity).

This topic will address intrapartum management of pregnant women with HIV, breastfeeding for postpartum women with HIV, and antiretroviral management for their infants in resource-rich settings. In the United States, the Department of Health and Human Services publishes guidelines on the evaluation and management of pregnant women with HIV, which are updated on an ongoing basis [4]. Our recommendations below are largely consistent with these guidelines.

Other guidelines that are relevant to resource-rich settings include those from the American College of Obstetricians and Gynecologists (ACOG), the British HIV Association, and the European AIDS Clinical Society [5-7]. Links to these and other expert guidelines can be found in the society guideline links section below. (See 'Society guideline links' below.)

Information regarding antepartum evaluation, antiretroviral selection and management, and the pharmacokinetics of individual agents during pregnancy is found elsewhere. (See "Prenatal evaluation of women with HIV in resource-rich settings" and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings" and "Safety and dosing of antiretroviral medications in pregnancy".)

Information regarding the management of HIV during pregnancy in resource-limited settings and the prevention of HIV transmission during breastfeeding is found elsewhere. (See "Prevention of vertical HIV transmission in resource-limited settings" and "Prevention of HIV transmission during breastfeeding in resource-limited settings".)

Information regarding the diagnostic evaluation of HIV in infants born to mothers with HIV is found elsewhere. (See "Diagnostic testing for HIV infection in infants and children younger than 18 months".)

INTRAPARTUM MANAGEMENT

Mode of delivery — The approach to delivery mode depends on the viral load obtained within four weeks of delivery.

Women with plasma viral load ≤1000 copies/mL − In women with plasma HIV ribonucleic acid (RNA) ≤1000 copies/mL on antiretroviral therapy (ART), the overall incidence of transmission of HIV is low regardless of the mode of delivery (cesarean delivery versus standard vaginal delivery) or duration of membrane rupture, and a further decrease in transmission risk with cesarean delivery in such women is unclear [2,8-13]. In a meta-analysis that included observational studies conducted after the introduction of combination ART, pre-labor cesarean delivery at 38 weeks was not associated with decreased risk of HIV transmission compared with vaginal delivery among mothers who were on suppressive ART at the time of delivery [13]. Thus, we do not advise cesarean deliveries for these women, unless indicated for obstetric reasons (table 1).

Women with plasma viral load >1000 copies/mL − In women whose viral loads remain >1000 copies/mL beyond 34 weeks gestation (eg, women not taking ART, women presenting late in pregnancy, or women not responding to their current ART regimen), we recommend performing cesarean delivery at 38 weeks, prior to labor onset and rupture of membranes [4]. For these women, prelabor cesarean delivery decreases the risk of transmission to the child. This was illustrated by a meta-analysis of 15 prospective cohort studies performed prior to the widespread use of antiretroviral agents during pregnancy, in which the incidence of HIV transmission to the infant was 8.4 percent (72 of 857 births) with cesarean delivery versus 16.7 percent (1280 of 7676 births) with vaginal delivery [14]. The reduction in risk was similar when adjusted for use of zidovudine (versus nothing) and advanced HIV disease in the mother. A subsequent trial from the same time period that randomly assigned 436 women with HIV to cesarean or vaginal delivery produced similar results [15].

If such women present in labor or with ruptured membranes prior to scheduled cesarean delivery, management must be individualized and take into account the duration of the rupture of membranes/labor, current ART regimen, and HIV RNA level. If a woman is already in advanced labor or has prolonged rupture of membranes (≥4 hours), the benefit of cesarean may be lost, and consideration should be given to vaginal delivery.

Prior to the widespread use of ART during pregnancy, duration of membrane rupture was associated with risk of transmission [16]. However, in a more recent prospective study of deliveries between 1996 and 2008, there were no cases of HIV transmission among 493 pregnant women on ART with HIV RNA <1000 copies/mL near delivery, 144 of whom had rupture of membranes for more than four hours [10]. Among the 146 women on ART who had HIV RNA >1000 copies/mL (55 of whom had cesarean while the others had vaginal delivery), vertical transmission was 3.8 percent if duration of membrane rupture was less than four hours compared with 4.9 percent if four or more hours, and this difference was not statistically significant. Only viral load above 10,000 copies/mL was an independent risk factor for vertical transmission.

Intrapartum antiretrovirals — Women should continue taking their ART regimen as much as possible during labor and delivery or scheduled cesarean delivery. Additional administration of intrapartum intravenous zidovudine depends on the maternal HIV viral load within four weeks of anticipated delivery (table 1). If indicated, intravenous zidovudine (intravenously with a 2 mg/kg dose followed by a continuous infusion of 1 mg/kg/hour until delivery) should be given regardless of the presence of drug resistance to zidovudine.

For women on ART with HIV RNA ≤50 copies/mL consistently in late pregnancy and near the time of delivery (ie, four weeks before delivery) and no concerns regarding adherence or resistance to the regimen, intravenous zidovudine is not specifically recommended as it does not appear to further reduce the risk of vertical transmission in this setting [4,17,18]. Patients with acute or primary (first six months of infection) HIV during pregnancy should be treated similarly to women with HIV RNA ≥1000 copies/mL within four weeks before delivery.

For women on ART with HIV RNA between 50 and 1000 (ie, four weeks before delivery) or those who have had challenges consistently taking ART, the decision to use intrapartum intravenous zidovudine should be individualized; we suggest using it at these HIV RNA levels, and start the intravenous infusion at the time the woman presents in labor or prior to scheduled cesarean delivery. While observational data do not suggest a prevention benefit with intravenous zidovudine for this viral level range, the data are relatively limited. The transmission risk remains slightly higher with low-level viremia compared with undetectable levels; thus, some clinicians and patients may reasonably decide to use zidovudine in this setting. (See "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings", section on 'HIV viremia and risk of infant infection'.)

For women with HIV RNA ≥1000 copies/mL within four weeks before delivery, possible poor adherence, or unknown HIV RNA levels, we recommend intravenous zidovudine. We also suggest intravenous zidovudine for women with acute or primary (first six months of infection) HIV during pregnancy. For women scheduled for cesarean delivery, intravenous zidovudine should be given three hours before cesarean delivery. Women with HIV who present in labor should be given intravenous zidovudine immediately to decrease the risk of vertical transmission.

Zidovudine crosses the placenta rapidly and can provide pre-exposure prophylaxis to the fetus. In the PACTG 076 trial, combined antepartum zidovudine, intravenous zidovudine during labor, and six weeks of infant zidovudine prophylaxis reduced vertical transmission by 66 percent [19]. There are no randomized clinical trials evaluating the benefit of intravenous zidovudine during labor among women using current combination antiretroviral regimens. However, among 7917 women from the French Perinatal Cohort who had HIV RNA <400 copies/mL at delivery, receipt of intravenous zidovudine intrapartum was not associated with a decreased risk of vertical HIV transmission (transmission rates of 0.6 percent [42 of 7576] and 0 percent [0 of 341] with and without intrapartum zidovudine, respectively) [17]. In contrast, zidovudine receipt was associated with lower transmission rates among women who had HIV RNA ≥1000 copies/mL (2.9 percent [45 of 1561] versus 7.5 percent [8 of 107] without intrapartum zidovudine).

Specific circumstances

Preterm premature rupture of membranes — When membrane rupture occurs before 37 weeks gestation, decisions about timing of delivery should be based on best obstetric practices, taking into account risks of prematurity for the infant. The presence of HIV infection of the mother should not change management. In patients with viral load <1000 copies/mL at delivery, the duration of membrane rupture did not affect the risk of HIV transmission to the infant. As an example, in a study of 707 pregnant women with HIV receiving ART, there was no significant difference in perinatal transmission in women with membrane rupture less than four hours compared with greater than four hours (1.0 versus 1.9 percent) [10]. Of 493 participants with delivery viral load <1000 copies/mL, there were no cases of perinatal transmission despite ruptured membranes of up to 25 hours. Administration of antenatal corticosteroids to accelerate fetal lung maturity should be given if appropriate, as no data exist to suggest that these recommendations need be altered for women with HIV. When the decision is made to deliver, route of delivery should be according to obstetric indications.

Other intrapartum interventions — Obstetric management should minimize the duration of fetal exposure to maternal fluids and blood and avoid fetal scalp electrode monitoring when possible. The possible risks of other interventions during management of labor should be weighed against the obstetric indications and benefits. Artificial rupture of membranes and operative vaginal delivery (eg, with forceps or vacuum extractor) should generally be avoided in women with a viral level ≥50 copies/mL. Delayed cord clamping for 30 to 60 seconds after birth in vigorous term and preterm infants is recommended by the American College of Obstetricians and Gynecologists (ACOG) to improve iron stores and hemoglobin levels in the infant. This practice does not appear to affect the risk of HIV transmission. As an example, in a study of 64 mother-infant pairs, of whom all the mothers were receiving ART, the 32 infants with delayed cord clamping (120 seconds post birth) had higher hemoglobin levels at 24 hours and 1 month of age, no increased risk of jaundice or polycythemia, and no perinatal transmission compared with the infants who had early cord clamping (<30 seconds after birth) [20].

BREASTFEEDING — The risk of HIV transmission from mother to child through breastfeeding depends on maternal viral load, antiretroviral therapy (ART) adherence, infant ART prophylaxis, and whether the infant is exclusively breastfed or receives combination feeding of formula and breastmilk in the first six months of life [4].

In contrast with resource-rich settings, avoidance of breastfeeding in infants born to mothers with HIV in resource-limited settings is associated with increased infant morbidity and mortality. The prevention of vertical HIV transmission in breastfeeding individuals in resource-limited settings is discussed elsewhere. (See "Prevention of HIV transmission during breastfeeding in resource-limited settings".)

Mothers without viral suppression — For women without viral suppression or who are not on ART during third trimester of pregnancy and at delivery, we recommend not to breastfeed because of concern for increased risk of HIV transmission from mother to infant through breastmilk [4].

For individuals who choose to breastfeed despite these recommendations, clinicians should provide counseling on harm-reduction measures, including adherence to ART and infant prophylaxis [4,21]. (See 'Mothers with viral suppression' below and 'Infants of mothers without viral suppression' below and 'Continuation of ART' below.)

Mothers with viral suppression — For women who have been on ART with an undetectable viral load at delivery and at least through all of the third trimester of pregnancy, the risk of HIV transmission through breastmilk appears to be low, although not zero [4,22]. For women who desire to breastfeed, we provide specific guidance on how to minimize risk of transmission by following these practices:

Monitor maternal plasma HIV viral load every one to two months while the mother is breastfeeding.

Provide guidance on good breast care, including how to prevent and resolve overproduction of breastmilk, milk stasis, and breast engorgement.

Promptly identify and treat cracked, sore, and/or bleeding nipples, yeast infection, mastitis, and breast abscess.

Counsel mother to exclusively breastfeed up to six months of age. Mixed feeding with breastmilk and non-breastmilk replacements (formula or solid foods/liquids) prior to six months of age has been shown to increase the risk of HIV transmission.

When mother is ready to wean, advise to wean breastfeeding slowly over a two- to four-week period. Rapid weaning has been associated with increased risk of HIV shedding into breast milk [23-25] and development of milk stasis and breast engorgement during the weaning process. (See 'Mother with nipple damage, mastitis, or breast abscess' below.)

The data available on HIV transmission through breastfeeding come from resource-limited settings and mothers who initiated ART during second trimester of pregnancy or later. The data show in mothers who are on ART and have viral suppression, the risk of transmitting HIV through breastfeeding is low but not zero. As an example, in a study of over 2400 breastfeeding mothers with HIV randomized following delivery to either 18 months of maternal ART or infant prophylaxis for prevention of HIV transmission through breastfeeding, two transmissions occurred in mothers on ART who had viral loads <40 copies/mL [22]. In another study of 500 breastfeeding mothers with HIV, there were two transmissions in mothers on ART who had viral loads <50 copies/mL [26]. It remains unknown whether the risk of transmission through breastfeeding is lower in patients who are already virally suppressed at conception and continue to take ART throughout their pregnancy or in those taking newer ART regimens.

Special circumstances — There are certain circumstances in which the mother may need to stop breastfeeding, such as if there is damage to the nipple (eg, cracked, sore, and/or bleeding nipples), mastitis, or breast abscess, or if the mother develops viremia.

Mother with nipple damage, mastitis, or breast abscess — If the mother develops cracked, sore, and/or bleeding nipples, mastitis, or a breast abscess, we advise either to pump and flash heat the breastmilk to eradicate HIV prior to giving it to the baby or pump and discard the milk from the affected breast and continue to feed the baby from the unaffected breast. Flash heating the breastmilk entails placing a glass container containing the breastmilk in a small pot of water, heating the water to a boil, and then immediately removing the breastmilk from the water and letting it cool to room temperature prior to administering to the infant. Although supplementation with formula is also an option, it is associated with a slightly increased risk of HIV transmission in studies of women with HIV who were not receiving ART. Breastfeeding from the affected breast can resume without flash heating the milk when the breast recovers and no skin breakdown is noticeable. Some mothers may also choose to stop breastfeeding completely and transition to formula.

Newly detectable viral load while breastfeeding — If the mother is noted to have a newly detectable viral load, we counsel the mother to stop breastfeeding immediately and consider one of the following options until the viral load is repeated:

Give previously stored breastmilk that was expressed at a date when mother was virally suppressed. Pump and discard the breastmilk while viremia is present.

Pump and flash heat the breastmilk before feeding it to the baby.

Provide replacement feeding with formula, or if available, pasteurized donor human milk.

Consider stopping breastfeeding altogether and transition to formula.

The viral load should be repeated as soon as possible. If the repeat viral load is undetectable, breastfeeding may resume without any additional measures. If the repeat viral load has detectable virus, the clinician should advise the mother to stop breastfeeding and discuss the increased risk of HIV transmission to the infant if the mother decides to continue breastfeeding [4].

Infants with exposure to breastmilk from a person with a newly detectable viral load should be treated as high-risk breastfed infants for the remainder of the breastfeeding period. The infant should undergo an HIV nucleic acid diagnostic test as soon as possible to determine HIV infection status. Presumptive HIV therapy is recommended while diagnostic testing is pending and for the next six weeks if the infant tests negative for HIV (see 'Infant prophylaxis' below). If breastfeeding is continued, the infant should receive daily single-drug antiretroviral prophylaxis (nevirapine or lamivudine) throughout breastfeeding and for one to four weeks after weaning to minimize the risk of vertical transmission. (See 'Breastfed infants' below.)

INFANT PROPHYLAXIS — We administer antiretroviral postexposure prophylaxis to all infants born to mothers with HIV to decrease the risk of HIV acquisition. Infant antiretroviral prophylaxis should be initiated as soon as possible after birth, ideally within the first 6 to 12 hours of delivery [4,27]. The type of prophylaxis depends on the virologic status of the mother and mode of infant feeding (table 1). Diagnostic evaluation of HIV in infants is further discussed elsewhere. (See "Diagnostic testing for HIV infection in infants and children younger than 18 months", section on 'Mother with HIV'.)

Formula-fed infants

Infants of mothers with viral suppression on ART — The risk of HIV infection is low for infants born to mothers who are on antiretroviral therapy (ART) and have achieved a viral level <50 copies/mL within four weeks of delivery.

For infants born to mothers who have a sustained viral load <50 copies/mL (two consecutive tests collected ≥4 weeks apart) at and after 36 weeks of gestation, we administer two weeks of zidovudine if they meet all of the following criteria:

Born at ≥37 weeks of gestation

Born 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 at least 10 consecutive weeks of ART during pregnancy

Has not demonstrated any evidence of poor adherence to ART throughout the pregnancy

For infants who do not meet the above criteria but whose mothers have a sustained viral load <50 copies/mL, four weeks of zidovudine prophylaxis is generally appropriate (table 1 and table 2).

However, mothers with acute or primary HIV infection (HIV acquired within the past six months) during pregnancy have a greater risk of transmitting HIV to their infants regardless of viral suppression at the time of delivery [4]. In such cases, infants should receive combination ART prophylaxis (“presumptive treatment”) as is given to other infants with high risk of infection. (See 'Infants of mothers without viral suppression' below.)

The Department of Health and Human Services guidelines in the United States changed their recommendation to two weeks of zidovudine prophylaxis for infants with very low risk of HIV transmission [4]. However, some European nations have opted for no prophylaxis in such infants because the risk of transmission is low, data addressing the added benefit of prophylaxis in infants born to mothers who are virally suppressed on ART are limited, and adverse effects of zidovudine are minimized [28].

Infants of mothers without viral suppression — Because of a higher risk of HIV infection, we recommend combination antiretroviral prophylaxis for infants if the mother had any of the following risk factors (table 1):

Diagnosed with acute or primary HIV during pregnancy

Did not receive any ART during pregnancy

Only received intrapartum antiretrovirals

Received antepartum ART but did not achieve viral suppression within four weeks of delivery (ie, had a viral level ≥50 copies/mL)

We administer infant antiretroviral prophylaxis with a three-drug regimen (zidovudine, lamivudine, plus either treatment-dose [6 mg/kg] nevirapine or raltegravir (table 2)), which is effectively presumptive HIV treatment, for a six-week course [4]. Infants at risk of HIV-2 should receive a raltegravir-containing regimen, as nevirapine is not active against HIV-2. If zidovudine-associated toxicity arises or zidovudine is not available, abacavir can be used as an alternative to zidovudine. Prior to abacavir administration, negative testing for HLA-B*5701 allele should be confirmed.

If the infant is diagnosed with HIV infection, treatment should continue indefinitely (see "Diagnostic testing for HIV infection in infants and children younger than 18 months"). If the HIV nucleic acid amplification test at birth is negative and side effects or complications develop on the three-drug regimen, an alternative approach is to discontinue the lamivudine and nevirapine or raltegravir components at two weeks and continue zidovudine alone for the full six weeks.

Although we favor the three-drug regimen, other clinicians may opt for a two-drug regimen (eg, zidovudine plus prophylactic-dose nevirapine) in certain circumstances (eg, if the mother has been using ART throughout pregnancy but the viral level is slightly elevated above 50 copies/mL). The selection of infant prophylaxis regimen should 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.

The rationale for a combination antiretroviral regimen is to maximize the reduction in vertical HIV transmission and to provide presumptive treatment for infants at high risk of having acquired HIV infection until their HIV infection status has been ascertained, but the optimal combination regimen is uncertain. Although evidence suggests that combination antiretroviral prophylaxis is better than zidovudine monotherapy for such high-risk infants, there are no comparative data suggesting that a particular three-drug combination (zidovudine, lamivudine, plus either treatment-dose nevirapine or raltegravir) is superior to the two-drug regimen (zidovudine plus prophylactic-dose nevirapine).

The HIV Prevention Trials Network (HPTN) 040/Pediatric AIDS Clinical Trial Group 1043 study is the only randomized trial evaluating the efficacy of three combination prophylaxis regimens 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 [29]. 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 over eight days (2.2 percent) or six weeks of zidovudine plus two weeks of nelfinavir and lamivudine (2.4 percent). 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. 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 [30]. Raltegravir is available in a formulation appropriate for neonates and has defined neonatal dosing; in studies in antiretroviral-naïve adults with HIV, raltegravir is associated with greater and more durable viral suppression and less toxicity than the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz [31]. Thus, raltegravir may be a more potent option for prophylaxis (or presumptive therapy) than a nevirapine-based triple-drug regimen.

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. Preliminary data from 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 [32]. The three-drug regimen of zidovudine, lamivudine, and raltegravir is now also under study in some trials [33,34]. Data from these studies will guide future recommendations.

The threshold maternal viral level at which to prompt the use of combination infant prophylaxis is not definitively known. Observational data suggest that the lowest rates of transmission are observed when maternal viral load is below the level of assay detection (eg, <20 to 50 copies/mL versus 400 to 1000 copies/mL) [35,36]. However, there has been no study to demonstrate relative efficacy and safety of combination prophylaxis compared with zidovudine-only prophylaxis at these different thresholds of maternal viremia. We typically use maternal viral load >50 copies/mL as the threshold for combination infant prophylaxis.

Breastfed infants — Continuing ART prophylaxis in breastfed infants depends on maternal viral load and ART adherence.

Infants of breastfeeding mothers who are virally suppressed on ART – For infants of mothers who are consistently virally suppressed on ART and breastfeeding, continuation of infant ART prophylaxis is controversial. We favor extending infant prophylaxis with zidovudine to six weeks if the mother is consistently adherent to ART and maintains an undetectable plasma viral load [4]. Alternatively, the World Health Organization (WHO) recommends six weeks of nevirapine [37] while the British HIV Association (BHIVA) recommends two weeks of zidovudine [5].

There does not appear to be a benefit of continuing infant ART prophylaxis for the duration of breastfeeding when the mother is virally suppressed. 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) [38].

Infants of breastfeeding mothers who are not virally suppressed on ART – 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 recommend antiviral prophylaxis for the infant. We favor six weeks of infant presumptive HIV three-drug therapy followed by daily nevirapine prophylaxis for the infant until one to four weeks after weaning. If the mother has nevirapine-resistant virus or the infant does not tolerate nevirapine, alternatives include lamivudine or ritonavir-boosted lopinavir.

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-blind, 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, relative risk reduction 62 percent) [38].

We continue to monitor breastfed infants for HIV acquisition every three months during breastfeeding as well as four to six weeks, three months, and six months after cessation of breastfeeding. 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. 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 [4]. (See "Diagnostic testing for HIV infection in infants and children younger than 18 months", section on 'Mother with HIV'.)

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. Infant combination antiretroviral prophylaxis as given for high-risk infants should be initiated immediately if the rapid test is positive, while awaiting confirmatory HIV testing (table 1 and table 2) [4]. For mothers who were planning to breastfeed, breastmilk should be expressed and stored appropriately until all HIV test results are reviewed. (See 'Infants of mothers without viral suppression' above and "Screening and diagnostic testing for HIV infection".)

If testing confirmed that the mother does not have HIV, the mother can initiate breastfeeding without precautions and the infant’s prophylaxis regimen can be discontinued.

Neonatal drug safety and pharmacology — It is important to note that pharmacokinetic data to allow appropriate dosing recommendations in neonates are available only for zidovudine, lamivudine, abacavir, nevirapine, raltegravir, and nelfinavir, 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 non-specific 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 [30].

A phase 1, multicenter trial of full-term neonates exposed to HIV found daily raltegravir safe and well tolerated during the first six weeks of life [39]. 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 [40]; in the phase 1 trial, there were only two cases of mild nonserious bilirubin elevations in newborns receiving raltegravir.

The use of lopinavir-ritonavir in four preterm infants (two sets of twins) was associated with heart block that resolved after discontinuation of the drugs; thus, this drug is not recommended for use in neonates for prophylaxis of vertical HIV transmission, as it should not be administered to neonates before a postmenstrual age of 42 weeks and a postnatal age of at least 14 days [41]. Although a trial evaluating antiretroviral prophylaxis in breastfeeding infants did not detect differences in side effects among those who received lopinavir-ritonavir versus lamivudine (grade 3 or 4 events in 51 and 50 percent), the study drugs in this trial were not initiated until day 7 of life, and infants <2 kg were not enrolled [42].

POSTPARTUM MANAGEMENT

Continuation of ART — All women should continue antiretroviral therapy (ART) following pregnancy. This is consistent with recommendations in the United States and elsewhere to initiate and continue ART in all individuals with HIV, regardless of CD4 cell count or clinical state, to reduce the risk of disease progression and to prevent HIV sexual transmission, given findings from randomized clinical trials [43-45]. (See "When to initiate antiretroviral therapy in persons with HIV".)

In the postpartum period, adherence to an antiretroviral regimen may be particularly difficult. In a meta-analysis of studies of antiretroviral use during and after pregnancy, the pooled rate of adequate adherence (>80 percent of doses) in the postpartum setting was only 53 percent [46]. This finding highlights the importance of careful adherence counseling and social support during the postpartum period to mitigate the risk of poor compliance among those who continue an antiretroviral regimen.

Modification of the ART regimen may be appropriate if pregnancy-related factors (eg, pharmacokinetic issues or toxicity concerns) led to selection of an ART regimen that contains agents that are not preferred agents in nonpregnant individuals. (See "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load".)

Family planning — Family planning issues should be discussed with all women, and postpartum contraception should be offered. (See "HIV and women", section on 'Choice of contraception'.)

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 treatment in pregnant women" and "Society guideline links: HIV infection in infants and children".)

SUMMARY AND RECOMMENDATIONS

Introduction − In the United States and Europe, the risk of vertical HIV transmission has declined to historically low levels with the use of antiretroviral medications. The combined use of maternal antepartum, maternal intrapartum, and infant antiretroviral prophylaxis maximizes infant pre-exposure and postexposure prophylaxis to decrease the risk of HIV acquisition. (See 'Introduction' above and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings".)

Mode of delivery

For women who have a viral load >1000 copies/mL beyond 34 weeks gestation (eg, women not taking antiretroviral therapy [ART], women presenting late in pregnancy, or women not responding to their current ART regimen), we recommend prelabor cesarean delivery at 38 weeks to reduce the risk of HIV transmission to the infant (table 1) (Grade 1A). (See 'Mode of delivery' above.)

The mode of delivery for women on ART with viral load <1000 copies/mL ≤4 weeks prior to delivery depends on obstetric indications alone. (See 'Mode of delivery' above.)

Intrapartum ART use − Women should continue taking their ART regimen during labor and delivery or scheduled cesarean delivery. (See 'Intrapartum antiretrovirals' above.)

For women who have a viral load ≥1000 copies/mL or unknown viral levels in late pregnancy and around the time of delivery, we recommend intrapartum intravenous zidovudine to further reduce the risk of vertical transmission (table 1) (Grade 1B). Additionally, for women who were diagnosed with acute or primary HIV infection during pregnancy, we suggest intrapartum intravenous zidovudine, irrespective of viral load (Grade 2C), in order to further reduce the risk of vertical transmission.

We also suggest intrapartum intravenous zidovudine for women with HIV RNA between 50 and 1000 copies/mL and those who had inconsistent ART adherence (Grade 2C).

For women who have had viral load ≤50 copies/mL consistently in late pregnancy and around the time of delivery and have no concerns related to adherence or resistance to the regimen, intrapartum intravenous zidovudine is not associated with further reduction of HIV transmission.

Breastfeeding

For women without viral suppression or who are not on ART during third trimester of pregnancy and at delivery, we recommend not to breastfeed because of concern for increased risk of HIV transmission from mother to infant through breastmilk (Grade 1A).

For women who have been on ART with an undetectable viral load (<50 copies/mL) at delivery and at least through the third trimester of pregnancy, breastfeeding is an option that should be discussed with the patient. Although the risk of HIV transmission through breastmilk appears to be low in this patient population, it is not zero. Certain breastfeeding practices may minimize the risk of HIV transmission. (See 'Breastfeeding' above.)

Infant prophylaxis – Infant antiretroviral prophylaxis should be initiated as soon as possible, ideally within the first 6 to 12 hours of delivery. The precise prophylactic regimen depends on the mother's use of antepartum antiretroviral agents, their viral load within four weeks of delivery, and mode of infant feeding (breastfeeding versus replacement feeding). (table 1 and table 2). (See 'Infant prophylaxis' above.)

Formula-fed infants

-Infants of mothers with viral suppression (HIV RNA <50 copies/mL) – We suggest that infants at low risk of vertical HIV acquisition (mothers who maintained or acquired and maintained viral suppression on ART during their pregnancy) receive zidovudine postexposure prophylaxis after birth (Grade 2C). (See 'Infants of mothers with viral suppression on ART' above.)

-Infants of mothers without viral suppression (HIV RNA ≥50 copies/mL) – We recommend that all infants at high risk of vertical HIV acquisition (infants born to mothers who are not virally suppressed at delivery, have not received ART, had acute or primary HIV infection during pregnancy, or have adherence issues to ART) receive combination antiretroviral postexposure prophylaxis after birth (Grade 1B). (See 'Infants of mothers without viral suppression' above.)

Breastfed infants

-Infants of mothers with viral suppression (HIV RNA <50 copies/mL) – We recommend that all breastfed infants born to mothers who are virally suppressed at delivery and at least through all of third trimester receive antiretroviral prophylaxis (Grade 1B). (See 'Breastfed infants' above.)

-Infants of mothers without viral suppression (HIV RNA ≥50 copies/mL) – We do not recommend breastfeeding in mothers who are not virally suppressed and have not been consistently taking ART during pregnancy. However, if a mother chooses to breastfeed despite these recommendations, we recommend the infant receive antiretroviral prophylaxis to prevent HIV transmission via breastmilk (Grade 1A). (See 'Breastfed infants' above.)

Postpartum maternal ART use − Maternal ART should be continued postpartum in all patients with HIV, regardless of immune, clinical, or viral status. Adherence to ART during the postpartum period may be particularly problematic, and it is important to provide careful adherence counseling and social support during the postpartum period to mitigate the risk of poor compliance. (See 'Postpartum management' above and "When to initiate antiretroviral therapy in persons with HIV".)

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Topic 126417 Version 16.0

References

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