Desi M.

Newberry, DNP, NNP-BC ❍ Section Editor

Special Series: Congenital Infections

Congenital HIV
Prevention of Maternal to Child Transmission
Natalie Gordon Lynch, MSN, NNP-BC; Alexandra Kesler Johnson, MSN, NNP-BC

ABSTRACT
Background: Human immunodeficiency virus (HIV) is caused by a cytopathic lentivirus. HIV without adequate treatment
during pregnancy can result in maternal to child transmission (MCT) of the virus. Sequelae can include severe lifelong
morbidities, shorter life expectancies, and high mortality rates without antiretroviral therapy.
Purpose: To discuss epidemiological trends, pathophysiology, and clinical care guidelines including those for diagnosis,
treatment, and management of MCT of HIV in the United States. To emphasize the importance of prompt identification,
prophylaxis, and treatment of at-risk infants.
Methods: PubMed, CINAHL, MEDLINE, and Google Scholar were used to search key words—maternal to child trans-
mission, HIV, HIV in pregnancy, and neonatal HIV—for articles that were relevant and current. The World Health
Organization, Centers for Disease Control and Prevention, and UNICEF were also utilized for up-to-date information on
the topic.
Findings: Timely identification, intervention, and treatment are necessary to prevent MCT of HIV. Membrane rupture
duration is not associated with higher transmission rates with adequate viral suppression.
Implications for Practice: An evidence-based maternal/neonatal collaborative approach to care for the prevention and
management of MCT of HIV including adherence to combined antiretroviral therapy (cART) should be emphasized. Early
testing, prophylaxis, and treatment for neonates at risk, as well as education on current clinical care guidelines for
caregivers.
Implications for Research: Pregnancy complications of cART. MCT rates in conjunction with birthing practices and
restrictions among women living with HIV with low to undetectable viral loads.
Key Words: HIV, HIV in pregnancy, maternal to child transmission, neonatal HIV

uman immunodeficiency virus (HIV) is a of decline at present remains too slow to meet this

H cytopathic lentivirus, which is transmitted via

sexual contact, and/or contact with infected
blood or bodily fluids.1 HIV is a single-stranded
RNA virus that destroys CD4 cells, a type of white
blood cell, and breaks down the affected individual’s
immune system, causing a wide range of clinical
manifestations.1 HIV is a mass global public health
concern, which continues to kill individuals around
the world in large numbers each year.2 The advanced
stage of HIV infection is referred to as acquired
immunodeficiency syndrome (AIDS).1
In 2016, the United Nations Assembly set a goal to
decrease the number of new HIV infections world-
wide each year to fewer than 500,000 by the year
2020.3 In 2016, approximately 36.7 million people
in the world were living with HIV.2,4 While the annual
number of new HIV infections (worldwide, across all
age groups) has declined by 16% since 2010, the rate
Author Affiliations: Coastal Carolina Neonatology, and Neonatal
Intensive Care Unit, New Hanover Regional Medical Center,
Wilmington, North Carolina (Ms Lynch); and Intensive Care Nursery,
Duke University Hospital, Durham, North Carolina (Ms Johnson).
The authors declare no conflicts of interest.
Correspondence: Natalie Gordon Lynch, MSN, NNP-BC, 2212 South
17th St, Wilmington, NC 28401 (natalie.lynch@ccneo.net).
Copyright © 2018 by The National Association of Neonatal Nurses
DOI: 10.1097/ANC.0000000000000559
goal.2-4 Of the 36.7 million individuals living with
HIV worldwide, 17.8 million or approximately 50%
are women of childbearing age (>15 years), which
continue to add to the at-risk infant population on
which we focus for this article.4
Congenital HIV is transmitted from mother to
child and can be acquired prenatally or postnatally.
Prenatal maternal to child transmission (MCT) is
often referred to as vertical transmission and can
occur transplacentally, or during labor or birth. Ver-
tical transmission of HIV during labor or birth
occurs when the fetus is exposed to infected mater-
nal blood or bodily fluids, and/or the birth canal.
Postnatal MCT can occur through breastfeeding or
from the premastication of food by a person living
with HIV prior to infant feeding.1
HIV remains an incurable disease. However, with
an effective treatment regimen of combination anti-
retroviral (ARV) therapy (cART), individuals living
with HIV can lead long and healthy lives.2 cART is
an extremely important medical advancement,
which with adequate adherence can help control the
virus as well as prevent its transmission to others.2
The increasing use of cART is the primary catalyst of
the global decline of deaths from AIDS-related
causes by 48%, from 2005 to 2016.3 Unfortunately,
access to ARV therapy is not universal. It was esti-
mated in 2016 that as many as 24% of pregnant

330 Advances in Neonatal Care • Vol. 18, No. 5 • pp. 330-340

Copyright © 2018 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.

women living with HIV across the globe were with-
out access to treatment.2,4
The purpose of this article is to provide a concise
overview of MCT of HIV, and to equip those man-
aging the care of neonates with possible exposure to
HIV with clinical guidelines based upon the current
literature available regarding epidemiological trends,
pathophysiology, diagnosis, treatment, and manage-
ment of MCT of HIV in the United States.
PATHOPHYSIOLOGY
HIV-1 and HIV-2 are cytopathic lentiviruses belong-
ing to the Retroviridae family, known to cause dis-
ease in humans.1 Both evolved from the closely
related simian immunodeficiency viruses found in a
variety of sub-Saharan African nonhuman primate
species including chimpanzees and gorillas.1 The
HIV virus is extremely diverse and continually evolv-
ing.5 The viruses causing the current pandemic can be
broken down in to 4 groups: M (main), N (non-M/
non-O), O (outlier), and P (which is very closely
related to simian immunodeficiency viruses).5 Within
HIV-1, the group M subtype B variant is known to
be the most widely disseminated throughout the
globe.5 Therefore, this variant has become a model
for viral studies and is the most studied subtype, with
the majority of current HIV medications designed
utilizing the HIV-1 group M subtype B variant.5
Infection rates of HIV-2 remain very low in the
United States; therefore, the Centers for Disease Con-
trol and Prevention (CDC) guidelines for HIV testing
primarily focus on HIV-1.1 However, HIV-2 should
be considered in cases of infants born to women with
high risk factors for HIV-2 infection.1 In cases where
HIV-2 is likely or suspected, the CDC remains a
resource for proper HIV-2 diagnosis via clinician
referral request.1 Due to the overwhelming promi-
nence of HIV-1 in the United States, the remainder of
this article refers to HIV-1 simply as HIV, unless oth-
erwise stated. In addition, all recommendations stated
in this article regarding management, monitoring, and
treatment are specific to HIV-1.
HIV utilizes the DNA of the host CD4 cell to rep-
licate and spread throughout the body.1,6 The virus
requires reverse transcriptase, a viral enzyme, to
convert into a double-stranded DNA copy, which
then integrates into the host cell genome at random.1
Once the HIV viral genome integrates, it persists
within its host as a provirus.1 See Figure 1 for a
detailed description of the 7-step HIV life cycle.
EPIDEMIOLOGY
In 2016, 36.7 million people were living with HIV
worldwide.4 Children (<15 years) comprised 6% of
those HIV cases.4 The rate of MCT worldwide
remains high among untreated populations due to
Advances in Neonatal Care • Vol. 18, No. 5
Copyright © 2018 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
Congenital HIV 331
the lack of prompt diagnosis, disease awareness,
proper prenatal care, and access to ARV therapy.4
While new infection diagnosis among children has
declined by 47% worldwide since 2010, the rate of
new infections in this population remains high with
160,000 new infections diagnosed worldwide in chil-
dren younger than 15 years solely in the year 2016.4
New infection rates are known to disproportion-
ately affect non-Caucasian populations.1 For exam-
ple, higher infection rates exist among African
American and Hispanic women due to poverty, sub-
sequent tight social and sexual networks, and the
significant health inequity that often accompanies
poverty-stricken areas.7 A marked inequity in distri-
bution of MCT of HIV is observed in the African
American infant population, which has the highest
rate of transmission within the United States.7,8 Afri-
can American infants, which overall comprise
approximately 15% of infants in the United States,7
accounted for nearly 64% of all cases of perinatally
acquired HIV diagnoses in the year 2016.8
In the United States from 2011 to 2016, there were
1061 newly diagnosed cases of HIV in children
(13 years and younger), 777 of which were acquired
perinatally.8 In 2016 alone, there were 99 newly diag-
nosed cases of MCT in the United States.9 It is impor-
tant to also remember that HIV infection may or may
not be associated with classic signs and/or symptom-
atology of the disease.1 This is true especially in cases of
primary infection, where the mother may be unaware
of her serology status. These cases carry the highest
rates of MCT due to lack of knowledge or awareness
of HIV status. Of note, the CDC defines “children” as
persons of 13 years and younger and clumps all cases
of HIV in children together; there is no separation
between infants and older children in the national sur-
veillance reports published by the CDC each year.
Since the mid-1990s, the number of pediatric diag-
nosed cases of AIDS has decreased significantly due to
the development and implementation of antenatal HIV
testing, and thereby the decline of MCT of HIV.1 The
CDC recommends opt-out testing early in every preg-
nancy where the patient is informed of the test that will
be performed, unless she declines; as opposed to opt-in
testing, where the HIV screening must be requested by
the patient. In Birmingham, Alabama, after the imple-
mentation of opt-out testing in 1999, HIV testing rates
of women increased from 75% to 88%.10
In addition, since the mid-1990s, general practice
with the care of mothers living with HIV in industri-
alized nations has included: strict adherence to
cART during pregnancy, delivery, and the immedi-
ate postnatal period; planned cesarean section deliv-
eries prior to labor or rupture of membranes; and
the complete avoidance of breastfeeding.1 These
general practice guidelines have largely attributed to
the decreased incidence of MCT of HIV.1 Within the
current decade, MCT of HIV infections in the United
332 Lynch and Johnson

FIGURE 1

HIV replication life cycle. Image courtesy of the National Institute of Allergy and Infectious
Diseases (NIAID). Permission to reuse provided by the NIAID.

States has fallen by 32%.9 Despite the infection rate
of HIV in infants decreasing substantially in the
United States, the rate of new infection among ado-
lescents and young adults unfortunately remains on
the rise.1 Therefore, as long as there continue to be
new-onset infections within the childbearing popu-
lation, the risk for MCT of HIV will remain an
important issue within neonatal care.7
TRANSMISSION
Humans are the only known carriers of HIV, with
transmittable sources of infection including blood,
cervicovaginal secretions, semen, and human milk.1
Modes of transmission of HIV include sexual con-
tact (vaginal, orogenital, or anal), blood exposure
percutaneously (needle sticks, etc), blood or body
fluid exposure to mucous membranes (eg, mouth
and eyes), MCT (including in utero, at delivery, and
postnatally via breastfeeding), and contaminated
blood product transfusion.1 The primary source of
infection for women is via heterosexual transmis-
sion, and the primary source of infection for chil-
dren is MCT.8 For this reason, prevention of HIV
acquisition in women of childbearing age represents
a primary means of preventing congenital HIV.
www.advancesinneonatalcare.org

Copyright © 2018 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.

The MCT rate is significantly reduced with adher-
ence to cART throughout pregnancy, labor, and
delivery when paired with postnatal infant treat-
ment for a duration of 4 to 6 weeks.9 Early initiation
has been proven to lower the rate of MCT of HIV. In
women on cART prior to conception, the MCT rate
is approximately 0.2%, compared with first-trimes-
ter initiation at 0.4%, second-trimester initiation at
0.9%, and third-trimester initiation at 2.2%.11,12
However, in the absence of interventions during the
perinatal or delivery period, the rate of MCT of HIV
is approximately 25%.1,7
MCT of HIV is multifactorial and includes a mul-
titude of risk factors, which can be broken down
into maternal, labor and delivery, and postnatal fac-
tors. Maternal risk factors include increased mater-
nal viral load (which is associated with lower mater-
nal CD4 cell count), duration of HIV exposure, lack
of access to cART, interruption or nonadherence to
cART regimen during pregnancy, and little or no
prenatal care.1,6,13
Additional birth factors during labor and delivery,
which facilitate the transfer of viral material and
increase the risk of transmission during this period,
include late maternal infection diagnosis (during or
after delivery), elevated maternal viral load, low
CD4 counts, coinfections, and open lesions.1,6,13 The
risk of MCT of HIV increases with increasing dura-
tion of maternal rupture of membranes when the
maternal viral load is more than 1000 copies/mL.14
After birth the risks of MCT of HIV acquisition
remain. Postnatal risk factors of MCT include breast-
feeding, acquisition of acute infection while breast-
feeding, and premastication of food by individuals
living with HIV, which is then fed to infants.1,13
Worldwide, postnatal MCT of HIV remains high,
with the breastfeeding accounting for an estimated
one third to one half of all MCT of HIV globally.1
SCREENING GUIDELINES
Due to social and economic barriers to care, it is
estimated that only 70% of people living with HIV
are aware of their infection status.2 The American
Academy of Pediatrics recommends screening all
adolescents 16 to 18 years of age, regardless of
admission to sexual activity.15 Therefore, screening
is of the utmost importance. This is especially true in
the childbearing population, and all pregnant moth-
ers should have routine HIV screening in the first
trimester.6 Given the benefits of early identification
of pregnant women with HIV, the American College
of Obstetricians and Gynecologists recommends
that all pregnant women should be tested for HIV as
early as possible during their pregnancy unless they
specifically request not to be tested.16
HIV can be acquired at any time throughout preg-
nancy. High-risk individuals and women in areas
Advances in Neonatal Care • Vol. 18, No. 5
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Congenital HIV 333
with a high HIV incidence should receive repeat test-
ing in the third trimester.16,17 High-risk individuals
include intravenous (IV) drug users and pregnant
individuals with multiple partners during pregnancy.
In a CDC-sponsored multicenter study from 2001 to
2005, the Mother-Infant Rapid Interventions at
Delivery Study (the MIRIAD Study), Nesheim et al17
found additional screening in the third trimester to
be successful in the identification of newly acquired
primary HIV infection; enabling the initiation of
ARV prophylaxis prior to delivery. The continued
prevalence of HIV infection in women of childbear-
ing age epitomizes the recommendation for repeat
testing during pregnancy, regardless of history.17
DIAGNOSTIC TESTS
Diagnosis of HIV infection during the neonatal and
infancy period is based upon viral or viral nucleic
acid detection.1 Laboratory testing is required both
to rule out exposure to HIV and to rule out or con-
firm HIV infection in the neonatal and infancy
period. Laboratory testing of infants born to moth-
ers with unknown HIV status is crucial to rule out in
utero exposure. In these cases of unknown maternal
HIV status, newborn rapid HIV-1 antibody testing
should be completed as soon as possible following
delivery to detect exposure to the virus, so that ARV
prophylaxis can then be initiated within the first
12 hours of life if exposure to HIV is identified.18
This section outlines the widely used virologic tests
utilized in the identification of risk, and diagnosis of
HIV infection in infants and young children, as well
as provides essential details regarding timing of test-
ing, limitations, etc.
HIV-exposed infants, even those who are ultimately
found to be HIV negative, test positive with serologic
testing methods (eg, HIV-1 antibody test used to rule
out exposure) during the first 18 months of their lives
because maternal immunoglobulin G crosses the pla-
centa and lingers in the infant’s system.1,11,18 For this
reason, antibody assays, which are most commonly
used for HIV diagnostic testing in older children and
adults, are not utilized for testing in infants and young
children. Virologic tests, including HIV DNA and
RNA polymerase chain reaction (PCR), are the gold
standard and are required to diagnose viral infection
in infants younger than 18 months.1
HIV DNA PCR assay is the preferred diagnostic
test for HIV in infants and young children younger
than 18 months in the United States because it is
highly specific and sensitive in nature and is readily
available in most clinical settings.1 The HIV DNA
PCR assay is performed on peripheral mononuclear
cells from blood and can detect 1 to 10 proviral
DNA copies per sample.1 A positive HIV DNA PCR
by 48 hours of age is indicative of in utero infection.1
An important disadvantage to this testing method is
334 Lynch and Johnson
that it can provide false-negative results in the case
of non-B-subtype HIV-1 infections.1
HIV RNA PCR assay is the preferred diagnostic
test for non-B-subtype HIV-1 infections.1 This test
has similar specificity, availability, and sensitivity to
the HIV DNA PCR assay in infants and young chil-
dren younger than 18 months.1 One limitation to
this testing method is that false-negative results may
occur in combination with prophylactic ARV use.1
Timeline of testing is imperative both for prompt
diagnosis of HIV infection, and for the exclusion of
infection. It is necessary to obtain the first virologic
diagnostic testing within the first 2 weeks of life to
ensure early transition from prophylaxis to a cART
treatment regimen.1 Some experts even recommend
testing within the first 2 days of life in cases of pre-
sumed in utero infection to allow for prompt identi-
fication of neonatal infection.1 Diagnostic testing to
rule out HIV infection in neonates and infants with
both HIV DNA PCR and HIV RNA PCR should be
performed at the same intervals, including within
the first 2 to 3 weeks of age, and if negative then
again at 1 to 2 months of age, and if again negative
repeated at 4 to 6 months of age.1,19 A positive result
for HIV infection occurs if 2 samples taken at 2 dif-
ferent time points are both positive by either DNA
or RNA PCR assay.1 If the results of these tests are
all negative, infection with HIV is presumptively
excluded.1 It should be noted that initial blood sam-
pling should not be drawn from the umbilical cord
at delivery to determine HIV status, due to the risk
of contamination and false results.1
MANAGEMENT OF MATERNAL
TO CHILD TRANSMISSION
Prevention and management of MCT is a multifacto-
rial, multiphased process. Management strategies begin
prior to conception and extend well beyond delivery,
and in some cases even further into the infant’s life. Key
strategies in the prevention of MCT of HIV include
early identification, prompt treatment, and adherence
to cART with viral load suppression prior to concep-
tion, throughout pregnancy, and postnatally.6,9
Preconception
Prevention
The goal of women living with HIV desiring a preg-
nancy is to maintain a maximally suppressed vial
load prior to conception to both treat maternal infec-
tion and decrease MCT risk.6,11 cART also has clini-
cal benefit for both HIV-infected persons and their
uninfected partners with use in the form of preexpo-
sure prophylaxis (PrEP), which can be used to mini-
mize HIV transmission between serodiscordant part-
ners.11,20 PrEP is the use of cART by an HIV-uninfected
individual to maintain adequate blood drug levels to
Copyright © 2018 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
prevent HIV infection acquisition.11 The PrEP can be
used as a vital tool in the prevention of MCT. Women
who are HIV negative desiring pregnancy can utilize
PrEP as a means of infection prevention from their
serodiscordant partners living with HIV.
Management
The most effective way to reduce perinatal transmis-
sion of HIV is to maintain early and constant control
of HIV replication.12 Women living with HIV on
cART regimens, which were initiated prior to concep-
tion and continued throughout the entire pregnancy,
have been shown to have extremely low MCT of HIV
rates.21 Therefore, worldwide efforts to reduce MCT
of HIV are aimed at improving access to cART.22 All
women living with HIV, especially if desiring a preg-
nancy or already pregnant, should be initiated on
cART as early as possible.23
Antepartum
Prevention
The risk of MCT among mothers living with HIV is
1% or less with proper adherence to cART regimens.9
Treatment should be initiated at diagnosis and should
be continued throughout pregnancy and thereafter.21
Pregnant women with HIV should continue or be
started on similar cART to their nongestational peers,
unless specific fetal or maternal concerns warrant
otherwise.11,19 The risk of MCT is almost entirety
eliminated in cases of ongoing viral load suppression
at the time of conception and throughout pregnancy,
as evidenced by a study of 2651 HIV-exposed infants
in which there were zero perinatal transmissions in
this adequately treated and suppressed population.12
Management
Limited data exist regarding safety of use of indi-
vidual ARV drugs in pregnant women, with the
exception of zidovudine (ZDV). ZDV monotherapy
has not been associated with increased risk of
adverse fetal or maternal outcomes.6 Inflammation
is a major factor in preterm births, intrauterine
growth restriction, and preeclampsia. Inflammation
markers are higher in pregnant women with HIV
than in their negative counterparts; therefore, asso-
ciation of cART therapy with increased rates of pre-
term delivery may be falsely elevated.23 Despite the
risk, the benefits of cART for both maternal health
and the prevention of MCT greatly outweigh these
and any other associated risks.
Intrapartum
Prevention
It is estimated that 11% of women living with HIV
are undiagnosed, or unaware of their HIV status.11,17
Therefore, all women presenting in labor without
www.advancesinneonatalcare.org
 Congenital HIV 335

documented HIV status should have a rapid intra-
partum HIV test performed (see Figure 2 for a clini-
cal guideline flowchart, which begins with determin-
ing maternal HIV status).11 Rapid antibody testing is
vital to ensure ARV prophylaxis initiation within the
critical window of the first 12 hours of the infant’s
life if maternal diagnosis is positive.18 Testing is
imperative to prevention, as between 40% and 85%
of infants with HIV are born to women with
unknown viral status.11

FIGURE 2

Clinical care of the neonate exposed to HIV. A flowchart designed to aid in the clinical management of a
neonate with possible exposure to HIV.

Advances in Neonatal Care • Vol. 18, No. 5

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336 Lynch and Johnson
Management
The cultural norm of the past few decades has been to
avoid rupturing the membranes of pregnant women
living with HIV, to decrease the rate of MCT of HIV,
which is largely in part due to high risk of transmis-
sion during the birthing process. Recent studies have
challenged this current practice of the avoidance of
rupture of membranes, and whether it translates into
the current age of women living with HIV on cART.24
A single-center study, from 1996 to 2008, found an
association between membrane rupture duration and
MCT of HIV only among patients with a maternal
viral load of more than 1000 copies/mL.14 Duration
of prolonged rupture of membranes is not associated
with increased MCT of HIV among women with a
viral load of fewer than 1000 copies/mL.11,14,24
Another recent study with similar findings was
conducted with women on cART in the United King-
dom and Ireland from 2007 to 2012.25 This study by
Peters et al,25 which represents the largest cohort to
date of women living with HIV on cART, showed no
correlation of evidence between membrane rupture
duration and rates of perinatal MCT of HIV.25 This
study has been considered pivotal in excluding mem-
brane rupture duration in women on cART as an
independent risk factor for MCT of HIV.24 The
appropriation of this data can be utilized in practice
to allow for the normalization of obstetric manage-
ment of women living with HIV with undetectable
viral loads on cART.24 It is unlikely that current
practice norms will adopt early labor artificial rup-
ture of membranes in women living with HIV (even
on cART); however, this new research can put at
ease many of the concerns regarding presentation
with prolonged membrane rupture or in those with
medical indications for artificial rupture of mem-
branes.24 In the current era of cART regimens, which
have been shown to be highly effective, the overall
MCT rate of HIV in women with undetectable viral
loads on cART is the lowest it has ever been.25,26
Both elective cesarean sections and consistent
cART treatment throughout prenatal, intrapartum,
and neonatal periods have been shown to reduce
MCT of HIV.27 The results of a 15-year prospective
cohort study meta-analysis showed an 87% reduc-
tion in transmission among women on consistent
cART with delivery via elective cesarean section, as
compared with other delivery modes in the absence
of ARV therapy (adjusted odds ratio, 0.13; 95%
confidence interval [CI], 0.09-0.19).27
Current US guidelines recommend cesarean sec-
tion at 38 weeks, before the initiation of labor and
before rupture of membranes for women with a viral
load of more than 1000 copies/mL or in women with
unknown viral load.1,6 Elective cesarean section after
the onset of labor or spontaneous rupture of mem-
branes has not shown a decreased risk of HIV trans-
mission.6,11 Therefore, viral load, not HIV status
Copyright © 2018 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
alone, should be used to determine the mode of
delivery.6,11 The risks of cesarean section must also
be considered, which are numerous and are statisti-
cally higher for women living with HIV.28 When
compared with uninfected women, a study showed
women living with HIV who undergo cesarean sec-
tions to have a higher risk of complications includ-
ing infectious complications (CI, 1.18-2.35), surgi-
cal trauma (CI, 1.41-4.26), and extended hospital
stays (CI, 1.58-2.74).28
Postpartum
Prevention
The risk of MCT is significantly decreased with the
initiation of postnatal infant prophylactic courses.9
Prevention of MCT through postnatal treatment is
based solely on the knowledge of maternal HIV sta-
tus. Therefore, rapid HIV testing in mothers who
present in labor without documented HIV status is
crucial to ensure early ARV prophylaxis initiation
where warranted.
Management
Prophylactic treatment of newborns exposed to HIV
perinatally should begin as soon as possible, within
the first 6 to 12 hours of life following rapid HIV-1
antibody testing of the newborn (Table 1).6 Infants
born to mothers living with HIV on cART with sus-
tained viral suppression near delivery should receive
ARV prophylaxis, and do not require antibody test-
ing prior to initiation of prophylaxis.6 Prophylaxis
consists of a 4-week regimen of a single ARV drug,
usually ZDV.6 Infants born to mothers living with
HIV are considered at higher risk for transmission if
their mother did not receive antepartum or intrapar-
tum treatment, only received intrapartum ARV
drugs, received treatment but did not achieve viral
suppression near delivery, had a primary or acute
infection during pregnancy, or acquired a primary
HIV infection during breastfeeding.6 These infants at
a higher risk should receive a 4-week-long prophylac-
tic ARV regimen, or the initiation of empiric therapy,
which is the administration of a 3-drug cART regi-
men consisting of ZDV, lamivudine, and treatment
dose nevirapine (Table 1).6 The decision of whether
to treat with 4 weeks of prophylaxis or to initiate
empiric therapy is based on the clinician’s interpreta-
tion of the level of intrapartum risk. Current and
regularly updated US treatment recommendations,
for infants and adults, are provided free through the
US Department of Health and Human Services and
the National Perinatal HIV Hotline (see Table 2).
DRUG THERAPIES
First-line cART for MCT of HIV during pregnancy
includes 2 nucleoside reverse transcriptase inhibitors
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 Congenital HIV 337

TABLE 1. Neonatal ARV Dosing and Side Effects

Antiretroviral
Medication Zidovudine Lamivudine Nevirapine
Dosage Treatment and prophylaxis dosage Treatment and prophylaxis Treatment dosage
≥35-wk gestation dosage ≥37-wk gestation
• Birth to 4 wk of age: 4 mg/kg/ ≥32-wk gestation • Birth to 6 wk of age:
dose orally, twice daily • Birth to 4 wk of age: 6 mg/kg/dose orally
• When using a 10-mg/mL oral 2 mg/kg/dose orally twice daily
syrup: twice daily dose is 1 mL twice daily
for infants 2-3 kg, 1.5 mL for • Age 4-6 wk: 4 mg/kg/ 34- to <37-wk gestation
infants 3-4 kg, and 2 mL for dose orally twice daily • Birth to 1 wk of age:
infants 4-5 kg 4 mg/kg/dose orally
twice daily
≥30- and <35-wk gestation • Age 1-6 wk: 6 mg/kg/
• Birth to 2 wk of age: 2 mg/kg/ dose orally twice daily
dose orally, twice daily
• Age 2-6 wk: 3 mg/kg/dose Prophylaxis dosage
orally, twice daily Birth weight 1.5-2 kg
• Age >6 to 8 wk: 12 mg/kg/dose • 8-mg dose orally, once
orally, twice daily daily

<30-wk gestation Birth weight ≥2 kg

• Birth to 4 wk of age: 2 mg/kg/ • 12-mg dose orally, once
dose orally, twice daily daily
• Age 4-6 wk: 3 mg/kg/dose Note: guidelines provided
orally, twice daily for this medication are
Note: IV dosing is 75% of oral actual dosages, not in
dosing, and should be adminis- mg/kg
tered at the same intervals
Side effects Minimal toxicity reported with use, In combination with Limited data, however
risk for transient hematologic ZDV, increased risk for hematologic and mito-
toxicity (most often anemia, transient hematologic chondrial toxicity, have
neutropenia) toxicity been observed with the
use of multiple nucleo-
side reverse transcriptase
inhibitor drugs
Abbreviations: ARV, antiretroviral; IV, intravenous; ZDV, zidovudine.

and a nonnucleoside reverse transcriptase inhibi-
tor.22 However, despite over 20 years of the utiliza-
tion of cART in pregnancy, evidence on the safety of
its use in pregnant women is scarce.29 The evaluation
for safety of use remains complex due to the use of
combination, multidrug therapy.29 While the bene-
fits of ARV drugs are both undeniable and over-
whelming, they are not without risk.
Adverse pregnancy outcomes have been identified
in women taking cART prior to conception when
compared with those who initiated treatment after
conception, including preterm or very preterm deliv-
ery, and an increased incidence of low birth-weight
infants.21,30 Risks associated with cART and preg-
nancy include birth defects as well as perinatal, mater-
nal, and obstetric complications.23 Risks associated
with cART use in pregnancy are considered contro-
versial and are difficult to outline, as multiple differ-
ent drugs are utilized and initiated at different points
within and prior to gestation, thus yielding it nearly
impossible to pinpoint risks associated with each
ARV. However, research has shown that efavirenz
(a common ARV drug) has been found to have first-
trimester exposure teratogenic potential including
central nervous system malformations.23 Additional
concerns surrounding cART use in pregnancy include
the potential for toxicity to the developing fetus,
increasing the risk for mitochondrial diseases, cardiac
dysfunction, genotoxicity, and cancer.23
When cesarean section is advised, it is recom-
mended that patients receive IV ZDV for 3 hours
prior to surgery to further reduce transmission

TABLE 2. Current US Treatment Recommendationsa

US Department of Health and Human Services http://www.AIDSinfo.nih.gov
National Perinatal HIV Hotline 1-888-448-8765
aFree to clinical consultation on all aspects of perinatal HIV, including newborn care.

Advances in Neonatal Care • Vol. 18, No. 5

Copyright © 2018 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
338 Lynch and Johnson
risk.6,11 ZDV should be used regardless of maternal
resistance, as it readily crosses the placenta, provid-
ing preexposure and postexposure prophylaxis to
the infant.11 The exception to both rules are women
living with HIV with a viral load of fewer than 1000
HIV RNA copies/mL; this threshold of plasma levels
is used to determine both the need for IV ZDV and
for elective cesarean delivery.11
ZDV monotherapy is also adequate for prophylactic
treatment of the infant postnatally.6 Empiric therapy
for infants at higher risk of HIV transmission typically
includes a 3-drug cART regimen of ZDV, lamivudine,
and nevirapine.6 The ARV drugs of choice are the same
for both preterm and term infants; however, dosing is
different.6 See Table 1 for an age- and weight-based
dosing guide of the common ARV drugs used for both
prophylaxis and empiric therapy in infants.
BREASTFEEDING IN MOTHERS LIVING
WITH HIV
Breastfeeding among HIV-infected women in the
United States, and in other industrialized nations, is
contraindicated. With a multitude of safe formula
alternatives readily available, the risks of MCT of
HIV are greater than the benefits of breastfeeding.1
This is because HIV in human milk can be detected
even in the cART-regimented, virologically sup-
pressed population.1 Therefore, it is important that
women who present with unknown HIV status and
women with a positive initial test should not breast-
feed until HIV infection is definitively ruled out.11
However, the continued recommendation in other
parts of the world, even when there is no direct access
to cART, includes exclusive breastfeeding (EBF).31 Rec-
ommendations for high-risk or resource-limited areas,
such as in Southern and Eastern African populations,
include EBF as the key nutritional source for infants
due to its advantages, which outweigh the risk of MCT.
Associated environmental factors involved in this rec-
ommendation include those which are common causes
of childhood mortality in these resource-limited set-
tings, including contaminated water sources, which
increase the risk of pneumonia, diarrhea, and malnutri-
tion.31 Suppressive cART, whenever available, for
mothers and infants is recommended throughout
breastfeeding to decrease the risk of MCT.31 EBF is rec-
ommended in these resource-limited settings, regard-
less of access to cART, for the first 6 months of life
because it has shown to increase survival rates.31 Unless
social and environmental circumstances are considered
safe for replacement feeding, such as formula, EBF is
still the gold standard for infant nutrition.32
SIGNS AND SYMPTOMS
With timely diagnosis and intervention, clinical
manifestations of HIV as well as the progression to
Copyright © 2018 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
AIDS are rare occurrences among infants and chil-
dren living in industrialized nations.1 The most com-
mon early clinical sign of HIV in infants and chil-
dren is often unexplained fevers.1 Other early clinical
manifestations include generalized lymphadenopa-
thy, recurrent unexplained fevers, organomegaly,
failure to thrive, recurrent diarrhea, persistent and
often recurrent candidiasis (oral or diaper area), par-
otitis, hepatitis, central nervous system disease
(hypotonia, developmental delay, hyperreflexia,
etc), lymphoid interstitial pneumonia, and recurrent
invasive infections (bacterial, viral, and or fungal).1
LIFESPAN IMPLICATIONS
Since the mid-1990s, there has been a significant
decline in mortality and morbidity associated with
HIV in the United States and industrialized nations
due to the increasingly prominent use of cART.19
Childhood HIV mortality rates are at an all-time
low in industrialized nations due to recent medical
advances; therefore, the prospect of HIV-positive
children surviving into adulthood has increased sig-
nificantly.1 From 2011 to 2015, only 11 children liv-
ing with HIV in the United States died from compli-
cations associated with the virus.8
The advancement of illness to AIDS and multior-
gan failure at 6 months of age or earlier in children
living with HIV is considered a poor survival out-
come predictor,1 and without treatment the esti-
mated life expectancy for a patient diagnosed with
AIDS is 3 years.33 Due to the current acceleration of
the AIDS response worldwide, there has been a sig-
nificant decline in AIDS-related deaths; however,
despite these advances the number of deaths related
to AIDS remains all too high.3 In 2016 alone, there
were approximately 1 million deaths related to HIV/
AIDS globally.3
Persons living with HIV are also at risk for mor-
bidities including opportunistic infections, which are
infections that attack more readily in those individu-
als with a weakened immune system. Persons living
with HIV are at greatest risk for contracting an
opportunistic infection when their CD4 count falls
below 200 cells/μL.33 See Table 3 for a listing of com-
mon opportunistic infections within the United
States. These individuals are also at increased risk for
cancer,34 and pulmonary diseases including chronic
obstructive pulmonary disease, pulmonary hyperten-
sion, pulmonary fibrosis, and infections.35 There has
been a significant decrease in the incidence in these as
well as other comorbidities including pediatric HIV
encephalopathy, and malignant neoplasms due to the
consistent use of cART in industrialized nations.1
Children diagnosed with HIV are now living into
their 30s and 40s, and beyond.19 Since children in
the United States diagnosed with HIV are now liv-
ing, and even thriving, well into adulthood, it is
www.advancesinneonatalcare.org
 Congenital HIV 339

TABLE 3. Opportunistic Infections

Most common opportunistic infections
Less common opportunistic infections
Targeted chemoprophylaxis recommended
Invasive encapsulated bacteria, Pneumocystis jirovecii, varicella-
zoster virus, cytomegalovirus, herpes simplex virus, Mycobacte-
rium avium complex, and Candida species
Epstein-Barr virus, Mycobacterium tuberculosis, Cryptosporidium
species, Cystoisospora, Aspergillus species, and Toxoplasma
gondii
Tuberculosis, pneumocystis pneumonia, Toxoplasma gondii, and
disseminated Mycobacterium avium complex

important for care to be transitioned seamlessly
from pediatric management into adult management
as the child reaches adolescence and adulthood.1
Long-term cART is associated with both short-term
and long-term toxicities, and over time there is the
possibility of an ARV drug-resistant virus.19 Thus, it
is of great importance for HIV-infected infants and
children to be followed up by both pediatric and
adolescent HIV infection specialists, as these clini-
cians are equipped to manage medical, psychosocial
issues, life skills, education, and family-planning
needs of the patient.1
CONCLUSION
Key implementations to assist in the management of
MCT and subsequent congenital HIV infections
include early identification of mothers living with
HIV, viral suppression prior to conception and
throughout pregnancy, prophylaxis for infants at
high risk of contracting HIV, early treatment for
infants suspected and later confirmed to be HIV
positive, and continual routine evaluation of HIV
status in infants at risk due to suspected transmis-
sion. HIV infections are associated with increased
mortality and morbidities; therefore, prevention,
early prophylaxis, and intervention should be
priority.
Maternal viral load, when known, should be
used to determine the appropriate delivery mode
in cases of the maternal viral load fewer than
1000 copies/mL. EBF among women living with
HIV remains the gold standard in resource-limited
areas. However, in industrialized nations where
safe formula alternatives are available, breast-
feeding is not recommended due to the increased
risk of MCT of the virus. Infected infants should
be followed up closely throughout infancy and
childhood by appropriately qualified personnel.
Proper follow-up with skilled personnel is essen-
tial to monitor for toxicities, drug resistance, tol-
erance, and maintain compliance to cART
regimens.
Despite MCT of HIV rates remaining very low
with adequate treatment, the inability to eradicate
MCT will persist in the setting of continued new-onset
infections in women and girls of childbearing age. In
an attempt to prevent MCT of HIV, it is imperative to
focus on screening for all individuals of childbearing
age, increasing access to ARV therapy, and provision
of education to improve adherence to cART for all
individuals living with HIV.

Summary of Recommendations for Practice and Research

What we know:
What needs to be studied:
What we can do today:
• ARV therapy is recommended for the treatment and prophylaxis of HIV, and is
recommended lifelong for all individuals living with HIV, including pregnant
women.
• With prompt diagnosis, adequate treatment, and proper precautions, the rate of
MCT of HIV is extremely low.
• Breastfeeding is only recommended for women living with HIV in resource-lim-
ited settings where access to formula and other nutrition is scarce. (Breastfeed-
ing is not recommended in the United States due to easy access to formula.)
• Pregnancy implications of cART.
• Normalization of birthing practices of women living with HIV with low to unde-
tectable viral loads.
• Know the risk factors for mothers with HIV, and encourage third-trimester
screening.
• Know the risk factors for infants at risk for MCT of HIV.
• Identify at-risk infants and prioritize prompt testing, prophylaxis, and treatment.
• Educate seronegative mothers on HIV transmission prevention and risk factors.
• Educate mothers living with HIV on prevention of postnatal MCT of HIV,
including prevention of breastfeeding in non-resource-limited settings.

Advances in Neonatal Care • Vol. 18, No. 5

Copyright © 2018 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
340 Lynch and Johnson
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