(Last updated: August 6, 2015; last reviewed: August 6, 2015)
|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
General Considerations for Choice of Infant Prophylaxis
All HIV-exposed infants should receive postpartum antiretroviral (ARV) drugs to reduce perinatal transmission of HIV. In all situations, infant prophylaxis should be initiated as soon as possible after delivery. The 6-week neonatal zidovudine prophylaxis regimen is generally recommended for all HIV-exposed infants.1,2 However, a 4-week neonatal zidovudine prophylaxis regimen can be considered in full-term infants when the mother has received standard combination antiretroviral therapy (cART) during pregnancy with consistent viral suppression and there are no concerns related to maternal adherence (see Infants Born to Mothers Who Received Antepartum/Intrapartum Antiretroviral Drugs with Effective Viral Suppression below).3,4 Table 8 shows recommended zidovudine dosing based on gestational age, birthweight, and the status of maternal antepartum ARV regimens.
The risk of transmission is increased when maternal viral load at delivery is high or maternal antepartum and/or intrapartum prophylaxis was incomplete or not received. In these situations, the potential benefit of combining zidovudine infant prophylaxis with additional ARV drugs must be weighed against the potential risks to infants of multiple drug exposure. In the following sections, we present available data and recommendations for management of infants born to mothers:
In each of these situations, there is a spectrum of transmission risk that depends on a number of maternal and infant factors, including maternal viral load, mode of delivery, and gestational age at delivery. The risks and benefits of infant exposure to ARV drugs in addition to zidovudine will differ depending on where the mother/child falls in the risk spectrum. Thus, a generic recommendation cannot be made regarding use of combination drug regimens for infant prophylaxis. Each situation needs to be considered individually, balancing potential benefits (in terms of preventing perinatal transmission of HIV) with risks (in terms of toxicity to the infant). In addition, appropriate drug formulations and dosing regimens for neonates are incompletely defined and data are minimal on the safety of combination drugs in the neonate (see Short-Term Antiretroviral Drug Safety and Choice for Neonatal Prophylaxis and the Pediatric Antiretroviral Guidelines).
Data from the NICHD-HPTN 040/PACTG 1043 study have provided guidance for management of infants born to women who received no ARV prophylaxis during pregnancy. In that study, 1,746 formula-fed infants born to HIV-infected women who did not receive any ARV drugs during pregnancy were randomized to 1 of 3 infant prophylaxis regimens: the standard 6-week zidovudine regimen; 6 weeks of zidovudine plus three doses of nevirapine given during the first week of life (first dose at birth–48 hours, second dose 48 hours after first dose, and third dose 96 hours after second dose); and 6 weeks of zidovudine plus 2 weeks of lamivudine/nelfinavir. The risk of intrapartum transmission was significantly lower in the two- and three-drug arms (2.2% and 2.5%, respectively, vs. 4.9% for 6 weeks of zidovudine alone; P = .046 for each experimental arm vs. zidovudine alone).5 Although transmission rates with the two combination regimens were similar, neutropenia was significantly more common with the three-drug regimen than with the two-drug or zidovudine-alone regimen (27.5% vs. 15%, P <.0001). In other studies, significantly higher rates of neutropenia and anemia have been reported with co-administration of zidovudine and lamivudine to infants.6 Thus, based on comparable efficacy and reduced toxicity, the Panel recommends 6 weeks of zidovudine plus three doses of nevirapine for infants whose mothers have not received antepartum ARV drugs (Table 8).
Despite the paucity of available data, the use of combination ARV prophylaxis for infants in high-risk situations is increasing. Surveillance of obstetric and pediatric HIV infection in the United Kingdom and Ireland through the National Study of HIV in Pregnancy and Childhood noted that between 2001 and 2004, 9% of HIV-exposed infants received triple-drug prophylaxis compared with 13% between 2005 and 2008.7 Similarly, in an Internet-based poll of 134 U.S.-based perinatal HIV service providers, 62% reported using combination postnatal prophylaxis in high-risk situations in the past year. Zidovudine, lamivudine, and nevirapine was the combination regimen used most often.8 The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) has pooled data from 5,285 mother-infant pairs included in 8 European cohorts between 1996 and 2010 and evaluated the use of combination prophylaxis. Among the 1,105 infants receiving combination prophylaxis, 13.5% received zidovudine plus lamivudine, 22.7% received zidovudine plus single-dose nevirapine, 55.8% received zidovudine plus single-dose nevirapine plus lamivudine, and 4.4% received a regimen including a protease inhibitor (PI). In these observational cohorts, there was no difference in infant infection rates between one drug and combination prophylactic regimens.9 The authors concluded that the lack of difference may be related to residual confounding or the fact that combination prophylaxis may only be effective in a subset of infants. Canadian investigators have reported outcomes in 136 infants considered at high risk of acquisition who received treatment-level doses of triple ARV prophylaxis within 72 hours of birth. Of the infants born into scenarios associated with higher risk of HIV transmission; 12 were found to be HIV-infected; no major toxicities were identified.10
A case of a “functional cure” of HIV in an infant was reported in 2013.11 The infant was born by vaginal delivery at 35 weeks’ gestation to a woman who received no prenatal care and was diagnosed as HIV-infected by expedited testing during labor; delivery occurred before maternal intrapartum ARV prophylaxis could be given. At age 30 hours, the infant initiated a regimen of zidovudine, lamivudine, and nevirapine (the latter drug administered at a higher therapeutic dose rather than standard prophylactic dosing). The infant was found to have a positive HIV DNA polymerase chain reaction (PCR) in a sample obtained at age 30 hours and an HIV RNA level of 19,812 copies/mL on an HIV RNA PCR assay performed at age 31 hours. Based on these tests, the infant was continued on treatment for HIV infection, thought to be acquired in utero. Nevirapine was replaced by lopinavir/ritonavir at day 7 of life (Note: This decision preceded warnings from the Food and Drug Administration [FDA] against use of lopinavir/ritonavir in infants younger than age 14 days). At age 18 months, the mother discontinued therapy; levels of plasma RNA, proviral DNA, and HIV antibodies remained undetectable in the child for over 2 years on no therapy. Unfortunately, virologic rebound was identified shortly before the child turned 4 years of age. Of interest, another case of virologic rebound following 4 years of suppression in an infant treated since birth has subsequently been reported.12
There are two key safety issues related to the choice of ARV drugs in these infants. First, although the use of nevirapine to prevent perinatal transmission has been found to be safe in neonates and low-birthweight infants (see Antiretroviral Drug Dosing for Premature Infants), these prophylaxis-dose regimens target trough drug levels of 100 ng/mL, with peak levels averaging 1000 to 1500 ng/mL. However, there have been no studies in neonates under age 2 weeks or preterm infants to determine the appropriate dosing or safety of nevirapine administered at therapeutic doses, designed to maintain trough drug concentrations above 3000 ng/mL and peak levels below 10,000 ng/mL for treatment of HIV-infected individuals. Second, lopinavir/ritonavir, as used in the first infant described, is not recommended for neonates younger than age 14 days because of the potential for significant toxicity (see Short-Term Antiretroviral Drug Safety and Choice for Neonatal Prophylaxis). Therefore, the risks of this approach in terms of infant toxicity (particularly in preterm infants) and efficacy require further study before a general recommendation can be made.
In these and all other scenarios, decisions about use of combination ARV prophylaxis in infants should be made in consultation with a pediatric HIV specialist before delivery, if possible, and should be accompanied by a discussion with the mothers about potential risks and benefits of this approach.
The National Perinatal HIV Hotline
The National Perinatal HIV Hotline (888-448-8765) is a federally funded service providing free clinical consultation for difficult cases to providers caring for HIV-infected pregnant women and their infants, and can provide referral to local or regional pediatric HIV specialists.
Recommendations for Infant Antiretroviral Prophylaxis in Specific Clinical Situations
Infants Born to Mothers Who Received Antepartum/Intrapartum Antiretroviral Drugs with Effective Viral Suppression
The risk of HIV acquisition is small in infants born to women who received standard ARV prophylaxis regimens during pregnancy and labor and had undetectable viral loads at delivery or by scheduled cesarean section to mothers with low viral loads at delivery. The optimal minimum duration of neonatal zidovudine prophylaxis has not been established in clinical trials. In the United States, the standard 6-week infant zidovudine regimen has been recommended, based on data from PACTG studies 076 and 316 (both performed during an era when a greater proportion of women did not receive antenatal cART). In the United Kingdom and many other European countries, a 4-week neonatal zidovudine prophylaxis regimen is now recommended for infants born to mothers who have received cART regimens and have viral suppression, with no apparent increase in the overall HIV perinatal transmission rate.3,4 In addition, a 4-week zidovudine regimen has been reported to allow earlier recovery from anemia in otherwise healthy infants compared with the 6-week zidovudine regimen.13 Therefore, a 4-week neonatal zidovudine prophylaxis regimen can be considered in full-term infants when a mother has received standard cART during pregnancy with consistent viral suppression and there are no concerns related to maternal adherence.
In infants born to women with effective viral suppression, combining zidovudine with additional ARV drugs to reduce transmission risk is not recommended because the risk of transmission is low and any potential benefit would be very limited. Any potential benefits must be balanced by the known toxicities of ARV drugs in infants.
Infants Born to Mothers Who Have Received Antepartum/Intrapartum Antiretroviral Drugs but Have Suboptimal Viral Suppression Near Delivery
All infants born to women who have received antepartum/intrapartum ARVs but with suboptimal viral suppression near delivery should receive zidovudine for 6 weeks. No specific data address whether a more intensive combination infant prophylaxis regimen (two or three drugs) provides additional protection against transmission when maternal antepartum/intrapartum prophylaxis is received but viral replication near delivery is significant. Extrapolation of findings from the previously discussed NICHD-HPTN 040/PACTG 1043 study5 suggests that combination infant prophylaxis should be considered, depending on assessment of risk based on maternal viral load and mode of delivery. That decision should be made in consultation with a pediatric HIV specialist before delivery and accompanied by maternal counseling on the potential risks and benefits of this approach. Although there are no clinical trials to identify the optimal combination infant prophylaxis regimen, it is clear that combination regimens are being used in this and other scenarios with a higher risk of perinatal transmission in the United States, Europe, and Canada.7-10
Many data support the observation that the risk of perinatal transmission is related to maternal antepartum viral load in women on no ARV drugs as well as women receiving these drugs.14-16 Scheduled cesarean delivery is recommended for prevention of perinatal transmission in women who have received antepartum ARV drugs but who have detectable viremia (HIV RNA >1000 copies/mL) near the time of delivery (see Intrapartum Care and Transmission and Mode of Delivery). In PACTG 316, transmission occurred in 0% of 17 infants when maternal HIV RNA levels at delivery were >10,000 copies/mL and delivery was by scheduled cesarean delivery.2 However, not all women with detectable viremia near delivery will undergo cesarean delivery. The risk of acquisition of HIV will be higher in infants born to mothers with higher viral loads near delivery, particularly if delivery is vaginal. The gradient of transmission risk is based on HIV RNA levels. In the Women and Infants Transmission Study (WITS), the risk of transmission of HIV was ≤1.8% in women who received cART and had HIV RNA levels <30,000 copies/mL at delivery; it increased to 4.8% in women with HIV RNA levels ≥30,000 copies/mL.16
Infants Born to Mothers Who Received Only Intrapartum Antiretroviral Drugs
All infants whose mothers have received only intrapartum ARV drugs should receive the 2-drug regimen of 6 weeks of zidovudine plus 3 doses of nevirapine in the first week of life (first dose at birth to 48 hours, second dose 48 hours after first dose, and third dose 96 hours after second dose), based on the results of the NICHD-HPTN 040/PACTG 1043 study. Infant prophylaxis should be initiated as soon after delivery as possible. Infant prophylaxis is a critical component of prevention when no maternal antepartum ARV drugs have been received. The PETRA study demonstrated that intrapartum prophylaxis alone, without infant prophylaxis, is ineffective in reducing perinatal transmission.17 A study in Thailand indicated that longer infant prophylaxis with zidovudine (6 weeks versus 3 days) is required for optimal efficacy when maternal antenatal exposure to zidovudine is <4 weeks.18 In the NICHD-HPTN 040/PACTG 1043 trial, 41% of women received zidovudine during labor. Administration of intrapartum zidovudine did not affect transmission rates.5
Infants Born to Mothers Who Did Not Receive Antepartum or Intrapartum Antiretroviral Drugs
The 2-drug regimen of 6 weeks of zidovudine plus three doses of nevirapine in the first week of life (first dose at birth to 48 hours, second dose 48 hours after first dose, and third dose 96 hours after second dose) is recommended for infants born to mothers who did not receive antepartum or intrapartum ARV drugs based on the results of the NICHD-HPTN 040/PACTG 1043 study, which demonstrated increased efficacy of combination regimens in reducing intrapartum transmission compared with use of zidovudine alone in infants.5 Prophylaxis should be initiated as soon after delivery as possible.
The interval during which infant prophylaxis can be initiated and still be of benefit is undefined. In the New York State study, when prophylaxis was delayed beyond 48 hours after birth, no efficacy could be demonstrated.19 Data from animal studies indicate that the longer the delay in institution of prophylaxis, the less likely that infection will be prevented. In most studies of animals, ARV prophylaxis initiated 24 to 36 hours after exposure usually has been ineffective in preventing infection, although a delay in administration has been associated with decreased viremia.20-22 In the NICHD-HPTN 040/PACTG 1043 study, infant regimens were initiated within 48 hours of life and usually within 12 hours of life.5 Initiation of infant prophylaxis after age 2 days is not likely to be efficacious in preventing transmission and, by age 14 days, infection already would be established in most infants.23 Initiating prophylaxis as soon after delivery as possible increases its potential efficacy and minimizes potential harm, such as development of resistant virus, if infection has occurred.
Infants Born to Mothers with Unknown HIV Infection Status
Expedited HIV testing of mothers is recommended during labor for women with unknown HIV status and for mothers and/or infants as soon as possible after birth if expedited HIV testing was not performed during labor. Expedited test results should be available within 60 minutes. Commercially available antigen/antibody tests are preferred to those that test only for antibody. Oral fluid-based tests are not recommended for infant testing; blood or serum testing has notably better sensitivity in infants than does oral fluid testing.24 If expedited testing is positive, infant ARV prophylaxis should be initiated immediately, without waiting for the results of supplemental tests (see scenario: Infants Born to Mothers Who Did Not Receive Antepartum or Intrapartum Antiretroviral Drugs). Expedited HIV testing should be available on a 24-hour basis at all facilities with a maternity service and/or neonatal intensive care, special care or newborn nursery.
A positive initial test result in mothers or infants should be presumed to indicate maternal HIV infection until standard supplemental testing clarifies maternal status. A positive HIV antibody test in an infant indicates maternal but not necessarily infant HIV infection; diagnosis of HIV infection in infants younger than age 18 months requires virologic testing using a viral nucleic amplification test (NAT; includes DNA and RNA PCR and related assays). Initial positive HIV antibody tests in the mother can be confirmed using a recommended HIV-1/2 diagnostic testing algorithm.25 Supplemental tests should be performed on mothers (or their infants) as soon as possible after the initial positive test. If the test results on a mother (or infant) are negative, ARV prophylaxis can be discontinued. If the supplemental test results in the mother are positive or if the mother is unavailable or declines testing, an HIV NAT should be obtained urgently from the newborn to determine the infant’s HIV infection status. If the HIV NAT is positive, ARV prophylaxis should be promptly discontinued and the infant should receive treatment for HIV infection with standard cART according to the Pediatric Antiretroviral Guidelines . Clinicians should be aware of their state laws, as there is variability in the testing allowed without parental consent.
Breastfeeding should be stopped until HIV infection is confirmed or ruled out in a woman who is suspected of being HIV-infected based on an initial positive antibody test result. Pumping and temporarily discarding or freezing breast milk can be recommended. If HIV infection is ruled out, breastfeeding can resume. If HIV infection is confirmed, breastfeeding should be discontinued permanently.26
Infants Born to Mothers with Antiretroviral Drug-Resistant Virus
The optimal prophylactic regimen for newborns delivered by women with ARV drug-resistant virus is unknown. ARV prophylaxis for infants born to mothers with known or suspected drug resistance should be determined in consultation with a pediatric HIV specialist before delivery or through consultation with the National Perinatal HIV Hotline (888-448-8765).
Data from WITS suggest that in women who have mixed zidovudine-resistant and zidovudine-sensitive viral populations, the virus sensitive to rather than resistant to the drugs may be preferentially transmitted.27,28 Thus, the 6-week infant zidovudine prophylaxis (along with maternal intravenous [IV] intrapartum zidovudine prophylaxis) continues to be recommended, even when maternal zidovudine-resistant virus with thymidine-associated mutations is identified.
Some studies have suggested that ARV drug-resistant virus may have decreased replicative capacity (reduced viral fitness) and transmissibility.28 However, perinatal transmission of multidrug-resistant virus has been reported both in the United States and in international settings.29-33
The optimal prophylactic regimen for newborns of women with ARV resistance is unknown. Therefore, ARV prophylaxis for an infant born to a woman with known or suspected drug resistance should be determined in consultation with a pediatric HIV specialist, preferably before delivery. However, there is no evidence that neonatal prophylaxis regimens customized based on presence of maternal drug resistance are more effective than standard neonatal prophylaxis regimens.
Short-Term Antiretroviral Drug Safety and Choice for Neonatal Prophylaxis
Infant prophylaxis with zidovudine has been associated with only minimal toxicity, consisting primarily of transient hematologic toxicity (mainly anemia), which generally resolves by age 12 weeks (see Initial Postnatal Management). Data are limited on the toxicity to infants of exposure to multiple ARV drugs.
The latest information on neonatal dosing for ARV drugs can be found in the Pediatric Antiretroviral Guidelines. Other than zidovudine, lamivudine is the nucleoside reverse transcriptase inhibitor (NRTI) with the most experience in use for neonatal prophylaxis. In early studies, neonatal exposure to combination zidovudine/lamivudine was generally limited to 117,34,35 or 2 weeks.5 Six weeks of infant zidovudine/lamivudine exposure also has been reported; these studies suggest that hematologic toxicity may be increased over that seen with zidovudine alone, although the infants also had in utero exposure to maternal combination therapy.
In a French study, more severe anemia and neutropenia were observed in infants exposed to 6 weeks of zidovudine/lamivudine for prophylaxis plus maternal antepartum zidovudine/lamivudine than in a historical cohort exposed only to maternal and infant zidovudine. Anemia was reported in 15% and neutropenia in 18% of infants exposed to zidovudine/lamivudine, with 2% of infants requiring blood transfusion and 4% requiring treatment discontinuation for toxicity.6 Similarly, in a Brazilian study of maternal antepartum and 6-week infant zidovudine/lamivudine prophylaxis, neonatal hematologic toxicity was common, with anemia seen in 69% and neutropenia in 13% of infants.36
Tenofovir disoproxil fumarate (tenofovir) with and without emtricitabine has been investigated in several small studies to define the safety and pharmacokinetics (PKs) of the agents in newborns.37,38,39 However, at this time, tenofovir and emtricitabine are not generally recommended for use in infant prophylaxis by the Panel because data on appropriate dosing are limited and the safety of these agents in the neonate is not well defined.
Experience with other NRTI drugs for neonatal prophylaxis is more limited.40,41 Hematologic and mitochondrial toxicity may be more common with exposure to multiple versus single NRTI drugs.6,42-45
Nevirapine is the only non-nucleoside reverse transcriptase inhibitor drug with a pediatric drug formulation and neonatal prophylactic (but not therapeutic) dosing information (see the Adult and Adolescent Antiretroviral Guidelines).46 In rare cases, chronic multiple-dose nevirapine therapy has been associated with severe and potentially life-threatening rash and hepatic toxicity. These toxicities have not been observed in infants receiving prophylactic dosing with single-dose nevirapine, the two-drug zidovudine regimen plus three doses of nevirapine in the first week of life in NICHD-HPTN 040/PACTG 1043), or in breastfeeding infants receiving nevirapine prophylaxis daily for 6 weeks to 6 months to prevent transmission of HIV via breast milk.5,47-50 Resistance to nevirapine can occur, however, with exposure to nevirapine in infants who become infected despite prophylaxis.51,52 ARV drug-resistance testing is recommended for all HIV-infected infants before initiation of cART (see the Adult and Adolescent Antiretroviral Guidelines).
Of the PIs, pediatric drug formulations are available for lopinavir/ritonavir, ritonavir, darunavir, tipranavir, and fosamprenavir, but their use in neonates in the first weeks of life is not recommended due to lack of dosing and safety information. In addition, lopinavir/ritonavir oral solution contains 42.4% alcohol and 15.3% propylene glycol, and enzymes that metabolize these compounds are immature in neonates, particularly preterm infants. No PK data are available for any PIs in the first 2 weeks of life. PK data are available for treatment of HIV-infected infants aged 2 to 6 weeks with lopinavir/ritonavir. Although the lopinavir area under the curve (AUC) was significantly lower with dosing 300 mg lopinavir/75 mg ritonavir/m2 body surface area twice daily than observed for infants >6 weeks of age, treatment was well tolerated and 80% of 10 infants had viral control at 6 months.53 Studies are ongoing but data are not yet available for infants aged <2 weeks. However, in four premature infants (2 sets of twins) started on lopinavir/ritonavir from birth, heart block developed that resolved after drug discontinuation.54,55 In studies of adults, both ritonavir and lopinavir/ritonavir cause dose-dependent prolongation of the PR interval, and cases of significant heart block, including complete heart block, have been reported. Elevation of 17-hydroxyprogesterone and dehydroepiandrosterone-sulfate has also been associated with administration of lopinavir/ritonavir compared with zidovudine in the neonatal period. Levels of 17-hydroxyprogesterone were greater in infants who were also exposed to lopinavir/ritonavir in utero compared with those exposed only in the neonatal period. Term infants were asymptomatic but three premature newborns experienced life-threatening symptoms compatible with adrenal insufficiency, including hyponatremia and hyperkalemia with, in one case, cardiogenic shock.56 Based on these and other post-marketing reports of cardiac toxicity (including complete atrioventricular block, bradycardia, and cardiomyopathy), lactic acidosis, acute renal failure, adrenal dysfunction, central nervous system depression, respiratory complications leading to death, and metabolic toxicity,57 predominantly in preterm neonates, the FDA now recommends that lopinavir/ritonavir oral solution not be administered to neonates before a postmenstrual age (first day of the mother’s last menstrual period to birth plus the time elapsed after birth) of 42 weeks and a postnatal age of at least 14 days.
Raltegravir is the only integrase inhibitor with an available pediatric drug formulation. However, there are no PK and safety data on its use during the first weeks of life and it is not FDA-approved for use in infants aged <4 weeks or weight <3 kg. Raltegravir readily crosses the placenta; its elimination was highly variable and extremely prolonged in some infants following maternal dosing. Raltegravir competes with bilirubin for albumin binding sites, which could increase unbound (free) unconjugated bilirubin levels in the neonate.58 An in vitro study has demonstrated that the effect of raltegravir on neonatal bilirubin binding is unlikely to be clinically significant unless raltegravir concentrations 50- to 100-fold higher than typical peak concentrations with usual dosing are reached.59 Use of raltegravir in neonates is not recommended until adequate PK and safety data are available.
Neonatal Antiretroviral Drug Dosing
All HIV-Exposed Infants
|ZDV||≥35 weeks’ gestation at birth: 4 mg/kg/dose PO twice daily, started as soon after birth as possible and preferably within 6–12 hours of delivery (or, if unable to tolerate oral agents, 3 mg/kg/dose IV, beginning within 6–12 hours of delivery, then every 12 hours)||Birth through 4-6 weeksa|
|ZDV||≥30 to <35 weeks’ gestation at birth: 2 mg/kg/dose PO (or 1.5 mg/kg/dose IV), started as soon after birth as possible, preferably within 6–12 hours of delivery, then every 12 hours, advanced to 3 mg/kg/dose PO (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days||Birth through 6 weeks|
|ZDV||<30 weeks’ gestation at birth: 2 mg/kg body weight/dose PO (or 1.5 mg/kg/dose IV) started as soon after birth as possible, preferably within 6–12 hours of delivery, then every 12 hours, advanced to 3 mg/kg/dose PO (or 2.3 mg/kg/dose IV) every 12 hours after age 4 weeks||Birth through 6 weeks|
|Additional Antiretroviral Prophylaxis Agents for HIV-Exposed Infants of Women who Received No Antepartum Antiretroviral Prophylaxis
Initiated as soon after delivery as possible
In addition to ZDV as shown above
|Birth weight 1.5–2 kg: 8 mg/dose PO
Birth weight >2 kg: 12 mg/dose PO
|Three doses in the first week of life:
|a A 6-week course of neonatal zidovudine is generally recommended. A 4-week neonatal zidovudine prophylaxis regimen may be considered when the mother has received standard ART during pregnancy with consistent viral suppression and there are no concerns related to maternal adherence.
Key to Abbreviations: ART = antiretroviral; IV = intravenously; NVP = nevirapine; PO = orally; ZDV = zidovudine
The recommended dose of zidovudine for post-exposure prophylaxis in full-term neonates is 4 mg/kg body weight orally (PO) twice daily, beginning as soon after birth as possible and preferably within 6 to 12 hours of delivery (see Table 8).17,47,60-67 Some PK studies suggest that the standard neonatal zidovudine dosing regimen might be excessive and associated with bone marrow and metabolic toxicity, but no alternative dosing regimens have been studied.68,69 If an infant is unable to tolerate oral medications, the zidovudine prophylaxis regimen can be administered IV. The zidovudine dosing requirements differ for premature infants and term infants (see Table 8 and Antiretroviral Drug Dosing for Premature Infants).
PKs and safety of the single-dose nevirapine regimen to mother and infant70 and chronic prophylactic nevirapine administration to infants to prevent HIV transmission during breastfeeding have been studied.71 The three-dose extended nevirapine regimen that was used in NICHD-HPTN 040/PACTG1043 and is recommended for HIV-exposed infants whose mothers did not receive ARV drugs during the antepartum period has also been studied.46 Nevirapine concentrations were measured in 14 newborns participating in a PK substudy during the second week of life and in single samples from 30 more newborns on Days 10 to 14. The median nevirapine elimination half-life was 30.2 hours (range: 17.8–50.3 hours) and the concentration remained greater than the target of 100 ng/mL in all infants through Day 10 of life.
Antiretroviral Drug Dosing for Premature InfantsDosing recommendations for premature infants are available for only zidovudine (prophylaxis and therapy) and nevirapine (prophylaxis only) (see Table 8). Zidovudine is primarily cleared through hepatic glucuronidation to an inactive metabolite; this metabolic pathway is immature in neonates, leading to prolonged zidovudine half-life and decreased clearance compared with older infants. Clearance is further decreased in premature infants because their hepatic metabolic function is less mature than in term infants.72,73 The recommended zidovudine dosage for preterm infants is shown in Table 8.
Breastfeeding Infants of Mothers Diagnosed with HIV Infection PostpartumBreastfeeding should be stopped until infection is confirmed or ruled out in women who are breastfeeding and suspected to have become HIV infected. Pumping and temporarily discarding or freezing breast milk can be recommended to mothers who are suspected of being HIV infected but whose infection is not yet confirmed and who want to continue to breastfeed. If HIV infection is ruled out, breastfeeding can resume. Breastfeeding is not recommended for women with documented HIV infection in the United States, including those receiving cART (see Infant Feeding Practices and Risk of HIV Transmission).75