www. AJOG .

org

Recommendations for human immunodeficiency virus

screening, prophylaxis, and treatment for pregnant
women in the United States
Denise J. Jamieson, MD, MPH; Jill Clark, MPH; Athena P. Kourtis, MD, PhD, MPH; Allan W. Taylor, MD, MPH;
R
Margaret A. Lampe, MPH, RN; Mary Glenn Fowler,
In the MD,
UnitedMPH;
States,Lynne M.human
current Mofenson, MD
immunodeficiency virus (HIV) testing guidelines
recommend an opt-out approach for pregnant women, whereby HIV testing is
incorporated routinely into the standard panel of prenatal tests with the option to
decline. Current recommendations for the initiation of treatment of HIV infection in
ecommendations regarding hu- pregnant women are the same as those for nonpregnant women. However, the special
man immunodeficiency virus circumstances of pregnancy raise additional issues that are related to potential drug
toxicity to the mother and fetus, which affect the choice of antiretroviral drugs to be
(HIV) screening, prophylaxis, and used. For HIV-infected pregnant women who do not require therapy for their own
health, antiretroviral drugs are recommended for prevention of mother-to-child trans-
treatment of pregnant women have mission. Highly active antiretroviral therapy is recommended for all women with HIV
evolved considerably in the United RNA levels of 1000 copies/mL, along with consideration of elective cesarean
1
delivery. For women with HIV RNA levels of 1000 copies/mL, a 3-part zidovudine
States over the last 25 years, reflecting prophylaxis regimen (prenatal, intrapartum, and neonatal) should be used alone or in
combination with other antiretroviral drugs.
changes in the epidemic and the sci-
ence of prevention. Not long after ac- Key words: HIV testing and treatment, pregnancy

quired immunodeficiency syndrome

2

(AIDS) was first described in 1981, the

3
possibility of mother-to-child trans-
mission of the new syndrome was
proposed. Scientific consensus that
gathered to support this theory in- 3

cluded reports of infants with AIDS

who had not had significant contact
with their mothers after delivery,
which suggested that infection had oc-
4
curred before or during birth. Even

though significant gaps still exist in our nation antiretroviral prophylaxis, cesar- phylaxis, and treatment of HIV-in-
knowledge of the exact timing and ean delivery, and avoidance of breast- fected women that have contributed to
mechanisms of mother-to-child trans- feeding. In addition, the treatment of this remarkable public health success
mission of HIV, substantial evidence HIV disease during pregnancy has in the arena of mother-to-child HIV
has accumulated to document the risk changed considerably, with an increas- transmission.
of mother-to-child transmission, and ing proportion of women receiving
concerted research efforts have brought highly active antiretroviral therapy
about a dramatic decrease in such trans-
mission, at least in the industrialized throughout pregnancy. This article
describes the evolution of US recom-
T HE E VOLUTION OF THE
world, with interventions such as combi-
mendations for HIV screening, pro- C ENTERS FOR D ISEASE
C ONTROL AND P REVENTION
(CDC) HIV S CREENING
G UIDELINES FOR P REGNANT
From the Division of Reproductive Health, National Center for Chronic Disease Prevention W OMEN
and Health Promotion (Drs Jamieson and Kourtis) and the Division of HIV/AIDS
Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention (Drs The CDC released its first set of recom-
Taylor and Ms Lampe), Centers for Disease Control and Prevention, Atlanta, GA; Northrop mendations for HIV testing of pregnant
Grumman Information Technology, CDC Information Technology Support, Atlanta, GA women in 1985. These recommenda-
(Ms Clark); Johns Hopkins Medical School, Department of Pathology, Makerere tions acknowledged that the only avail-
University-Johns Hopkins University Research Collaboration, Kampala, Uganda (Dr able strategy for reducing the risk of peri-
Fowler); Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child
natal transmission was pregnancy
Health and Human Development, National Institutes of Health, Bethesda, MD (Dr
Mofenson).
prevention and that the benefits of
knowing one’s HIV status were few,
Received Dec. 14, 2008; accepted Mar. 31, 2009. given the lack of treatment options. The
1985 recommendations identified cer-
Reprints: Denise J. Jamieson, MD MPH, Centers for Disease Control and Prevention, 4770
Buford Highway, Mailstop K34, Atlanta, GA 30341. djj0@cdc.gov.
tain groups of women who were at high
risk for HIV infection who should be
0002-9378/$32.00 counseled regarding HIV and offered
© 2007 Mosby, Inc. All rights reserved. testing. These groups included women
with signs and symptoms of infection,
doi: 10.1016/j.ajog.2007.03.087

S26 American Journal of Obstetrics & Gynecology Supplement to SEPTEMBER2009

www.AJOG.org
Supplement

The announcement of an intervention

social effects that result from HIV
intravenous drug users, women who
were born in countries with a higher bur- that offered significant protection infection. 9

den of heterosexual transmission of short-term side effects of zidovudine against HIV infection for infants was a
HIV, sex workers, and sex partners of therapy detected for women or their in- turning point for perinatal HIV preven-
men at increased risk. Nonpregnant tion strategies. Although stigma and dis-
women with positive test results could be crimination against persons with HIV
encouraged to delay pregnancy. How- and AIDS were still present, there were
ever, women who were already pregnant now real benefits to learning one’s10 HIV
could be offered only additional medical status. Treatments for the protection of
and support services to manage oppor- an individual’s health had been available
tunistic infections and psychologic con- for several years, and now prophylaxis
cerns and be advised not to breastfeed could be provided to pregnant women to
their infant because of the potential for lower the risk that they would pass the
transmission of HIV through breastfeed- virus to their children.
ing. These guidelines did not endorse
routine testing of all women or counsel- In response to this development, the
9
ing and testing among women who were CDC developed new recommendations
considered not at high risk. This recom- for HIV testing among pregnant women
mendation was motivated by concern in 1995. For the first time, the US Public
about the interpretation of test results in Health Service recommended routine
low prevalence populations (ie, the re- HIV counseling and voluntary testing
percussions of false positive results in an for all pregnant women. Increasing sci-
environment in which considerable entific data on the safety and effective-
stigma and fear surrounded a diagnosis 5,6 ness of zidovudine for prevention of
of HIV infection). mother-to-child HIV transmission and
some advances in advocacy and protec-
Only a few years passed, however, be-
tions for persons who were infected with
fore it became apparent that risk-based
HIV had shifted the balance of benefits
screening was failing to identify substan-
and risks. However, these guidelines
tial numbers of infected women.
maintained a strong emphasis on the
Many physicians and public health offi-
provision of counseling before and after
cials believed that being able to notify a
testing, specific informed consent, and
woman of her HIV status was important
enough to justify expanded screening be- the voluntary nature of testing. The rec-
yond defined risk groups, despite the few ommendations stated that pretest coun-
options for treatment of a woman’s own seling should include information on
disease or prevention of perinatal HIV risk behaviors, the risk of mother-
transmission. to-child transmission if the woman were
infected, and the availability of therapy
In 1994, 1 of the most significant to reduce this risk. Provisions were also
breakthroughs in the history of the HIV/ included to ensure that women who de-
AIDS epidemic was announced. On Feb- clined testing, or declined treatment if
ruary 21, 1994, the Pediatric AIDS Clin- positive, were not denied care or sub-
ical Trials Group (PACTG) announced jected to discrimination. After the re-
results of a randomized, double-blinded ceipt of positive HIV test results, the
clinical trial, PACTG 076, that had dem- guidelines stated that women should re-
onstrated that a 3-part regimen of ceive posttest counseling that included
zidovudine (starting in the second tri- an explanation of the clinical implica-
mester of gestation and continuing in la- tions of a positive test result, information
bor and to the infant for 6 weeks after about HIV-related medical and other in-
11
birth) was effective in lowering the risk tervention services, the risk for mother-
of perinatal HIV transmission by ap- to-child HIV transmission and ways to
proximately two-thirds. In addition to reduce this risk, the prognosis for infants
being effective, zidovudine was found to who become infected, reproductive op-
be safe in this setting, with no serious or tions, recommendations to abstain from
breastfeeding, and an assessment of the In 1996, Congress passed the Ryan
White CARE Act, which provided fund-
ing for testing and treatment and addi-
tional strategies to combat the HIV/
AIDS epidemic. A provision of this
legislation called on the Institute of Med-
icine to conduct an evaluation of state
efforts to reduce mother-to-child HIV
transmission and an analysis of the exist-
ing barriers to further reductions in
transmission in the United States. The
committee found that, despite consider-
able efforts to implement the US Public
Health Service recommendations, the
number of children who were born with
HIV remained too high, often because of
lack of timely diagnosis of maternal HIV
infection. Their central recommenda-
tion was to implement universal HIV
testing with patient notification as a rou-
tine component of prenatal care, a strat-
egy referred to as “opt-out”testing. They
stressed that extensive pretest counseling
had proved to be a barrier to providing
testing for many providers. Incorporat-
ing HIV testing into the standard panel
of prenatal tests could increase the num-
ber of women who were offered testing,
while still ensuring notification to the
patient that testing would be done and
preserving her option to decline. Associ-
ated recommendations that were de-
signed to increase the proportion of
pregnant women who were tested for
HIV included educating prenatal pro-
viders on the value of HIV testing, adop-
tion of professional recommendations
and performance measures to encourage
testing, improvement of care for HIV-
infected persons, maintenance of federal
funding for perinatal prevention of HIV,
and collection of appropriate surveil-
lance data.

As a result of the Institute of Medicine

report, several professional groups, in-
cluding the American College of Obste-
tricians and Gynecologists and Ameri-
can Academy of Pediatrics, issued new
guidelines that supported the recom-
mendations of the Institute of Medicine
and endorsed universal HIV testing with
patient notification as a routine compo-
nent of prenatal care. The CDC con-

fants when compared with placebo. 7,8 potential for negative psychologic and vened consultations to discuss these rec-

Supplement to SEPTEMBER2009 American Journal of Obstetrics & Gynecology S27

 peated in the 2001 guidelines, which
Supplement again recommended retesting in the
third trimester (before 36 weeks of ges-

tation) for women who had tested nega-

tive but remained at high risk for acquir-
ommendations and published revised ing HIV. This recommendation was also
recommendations for HIV screening of strengthened by adding a caveat that
pregnant women in 2001 that replaced routine universal retesting could be con-
the 1995 recommendations. The revised 12 sidered in healthcare facilities with high
recommendations emphasized that HIV
HIV prevalence among women of child-
testing should be a routine part of prena-
bearing age. After the publication of
tal care and recommended
12 simplifica-
these recommendations, new analyses
tion of the testing process to reduce bar-
demonstrated that a second HIV test
riers to testing but maintained a strong 20
during the third trimester is as cost-ef-
commitment to the voluntary approach
to HIV testing. These guidelines also fective as other commonly accepted
recommended the provision of pretest
16 health interventions, even in popula-
counseling, with a preference for face-to- tions with relatively low HIV preva-
face counseling, but allowed for the pos- lence. In addition, emerging research
sibility of written or electronic formats. from New York has suggested an increas-
ing proportion of infants with perinatal
In 2002, a CDC assessment of prenatal 17 HIV infection are born to women who
HIV screening rates was published that acquire HIV infection during preg-
found that testing rates were generally nancy. These findings support ex-
18
lower in jurisdictions with laws that panded recommendations for a second
13
mandated pretest counseling and spe- HIV test in the third trimester. Although
cific written consent before an HIV test the latest recommendations continue to
21
(the “opt-in”approach) and were gener- note that a second screen may be consid-
ally higher in areas with opt-out test- ered in all areas, a second test is recom-
ing. After the publication of this study, mended specifically for all women in 22
14
the CDC issued a “Dear Colleague”letter states with elevated HIV incidence, for
that endorsed the practice of routinely women who are served in facilities in
incorporating HIV testing in the stan- which prenatal screening reveals a prev-
dard panel of tests for all pregnant 18 alence of at least 1 per 1000, and for
women with the option to decline. In women who are at high risk of acquiring
2006, the most recent CDC recommen- HIV infection.
dations for HIV testing were published.
Recommendations regarding HIV Before the release of the 2001 recom-
screening for pregnant women were in- mendations, new research demon-
22
corporated into general recommenda- strated reductions in the risk of
tions for all adults and adolescents, and mother-to-child HIV transmission,
opt-out HIV screening was recom- 19
even if antiretroviral prophylaxis was
mended for all adults aged 13-64 years not given during pregnancy and could
15
who seek care in healthcare settings, in- only be given during labor and/or to
cluding pregnant women. The 2006 the newborn infant. Therefore, the
guidelines codified and strengthened the 2001 guidelines also recommended
recommendation for opt-out screening that women with unknown status at la-
12
bor and delivery should be tested
in pregnant women. promptly to allow for intrapartum and
The 2006 recommendations also neonatal antiretroviral prophylaxis, if
strengthened the CDC’s recommenda- positive. Testing could be accom-
tion for rescreening during pregnancy. A plished either by expedited standard
second 9HIV test during pregnancy was testing (with return of results within 12
first mentioned in the 1995 guidelines, hours) or preferably with rapid testing,
which recommended that women who which could be done at the bedside, to
test negative early in pregnancy and con- allow the prompt 7initiation of antiret-
tinue to practice high-risk behavior roviral prophylaxis in women with a
should be retested during the third tri- positive HIV test while still in labor.
mester. The recommendations for a However, at the time the guidelines
second test during pregnancy were re- were published, only 1 rapid test was
 www.AJOG.org known or undocumented HIV status zidovudine as described in the PACTG
and reiterate recommendations to ini- 076 protocol. On June 6-7, 1994, the
tiate antiretroviral prophylaxis to pre- US Public Health Service convened a
vent mother-to-child HIV transmis- workshop of invited guests that included
sion based on the rapid test result, representatives from the medical, scien-
available commercially in the United without waiting for confirmatory re- tific, public health, and legal communi-
States. sults. These recommendations are ties to develop recommendations for the
Since 2001, several additional rapid also reflected in the most recent guid- use of zidovudine to reduce perinatal
ance from the American College of Ob- HIV transmission and to provide guid-
tests have been approved by the Food
stetricians and Gynecologists. ance for clinicians and public health pro-
and Drug Administration (FDA) for
fessionals in interpreting the results of
use in the United States, and additional
the PACTG 076 trial. Based on feedback
research has described the acceptabil-
from this workshop, the US Public
ity and accuracy of rapid testing during
Health Service Task Force, which was
labor and delivery. The Mother-Infant US P UBLIC H EALTH SERVICE G composed of obstetric and pediatric HIV
Rapid Intervention at Delivery study UIDELINES FOR P ROPHYLAXIS experts and federal agency representa-
found that rapid testing is feasible and AND T REATMENT OF HIV- tives, issued more extensive guidance for
accurate and delivers timely results for I NFECTED P REGNANT W OMEN the use of zidovudine to reduce perinatal
women in labor. The 2006 recom- Within 2 months of the release of the re- HIV transmission. These guidelines,
mendations specifically recommend sults from the PACTG 076 trial, interim which are now more than a decade old,
the use of a rapid HIV test for screening guidance was issued by the US Public
women who arrive in labor with un- Health Service that supported the use of

S28 American Journal of Obstetrics & Gynecology Supplement to SEPTEMBER2009

 other parts of the guidelines and sup-
www.AJOG.org plemental information.

23 The current Public Health Service

were notable for several features that are guidelines have evolved considerably
still reflected in the current 2006 guide- over time. They now contain informa-
lines such as (1) the inclusion of clini- tion on 20 antiretroviral drugs, the
cal situations, later termed clinical sce- FDA pregnancy category and informa-
narios, that present hypothetic clinical tion on placental passage, dosing and
scenarios with discussion and recom- pharmacokinetics during pregnancy,
and animal carcinogenicity and terato-
mendations to help clinicians with deci-
genicity studies. Most of the approved
sion-making and (2) the clear distinction
antiretroviral drugs are FDA pregnancy
between prophylaxis to prevent perina-
category B or C. However, efavirenz is
tal transmission as opposed to treatment
category D, which indicates that there is
for the benefit of the woman’s own
evidence of human fetal risk. Severe cen-
health. The guidelines emphasize that
tral nervous system defects, which were
pregnancy should not be a reason to de-
consistent with abnormalities that have
fer antiretroviral therapy when it is
been seen in animal studies, have been
needed. Although there is a need for an-
reported in 4 infants after first trimester
tiretroviral prophylaxis for the preven-
exposure of efavirenz-containing regi-
tion of transmission to the infant and al- mens. Therefore, efavirenz should be
though issues that are related to potential avoided during the first trimester. Be-
drug toxicity to mother and fetus affect cause efavirenz is a relatively popular
the choice of antiretroviral drugs that are choice for combination regimens and
used for treatment, these concerns because more than one-half of pregnan-
should be dealt with in the context of as- cies in the United States are unintended,
suring optimal treatment to preserve the it is critical that women who take efa-
mother’s health. virenz be counseled regarding the risks.
Women who are planning to become
In January 1998, updated guidelines pregnant should strongly consider the
were issued that included more general use of regimens that do not contain efa-
recommendations for the use of antiret- virenz or other drugs with teratogenic
roviral drugs in pregnancy, expanding potential.
the previous guidelines’focus on zidovu-
dine. By this time, there were 11 FDA- Current recommendations for treat-
approved antiretroviral drugs, and these ment of HIV infection in pregnant
powerful new drugs were being used in women are the same as those for the ini-
highly active drug combinations. The ti- 3 tiation of treatment in nonpregnant in-
tle of the document now included “ma- dividuals; in the United States, treatment
ternal health”,
24 which reflected further is recommended for all individuals with
emphasis on considerations beyond 3 25 a CD4 cell count of 200/mm or an
AIDS-defining illness and should be
mother-to-child HIV transmission to considered for individuals with a CD4
address issues for the pregnant woman’s 23 cell count of 350/mm . Standard
own health. After publication of these treatment for nonpregnant and preg-
guidelines, the Public Health Service nant women is highly active antiretrovi-
Task Force
23 began meeting by monthly ral therapy with 3 drugs. For HIV-
conference calls to review new evidence infected pregnant women who do not
and regularly update the recommenda- require therapy for their own health, an-
tions. The guidelines, which are now up- tiretroviral drugs are recommended for
dated several times a year, are posted on a the prevention of mother-to-child trans-
website so that revised guidelines can mission. In the United States, combina-
be disseminated more rapidly. Each tion therapy with highly active antiretro-
time the guidelines are posted, the viral therapy is also recommended for all
changes that are new since the last re- pregnant women with HIV RNA levels of
vision are highlighted so that the
reader can quickly review the most re- 1000 copies/mL. For women with HIV
cent changes. The guidelines also con- RNA levels of 1000 copies/mL, the
tain hyperlinks that link the reader to 3-part PACTG 076 zidovudine prophy-
laxis regimen can be used alone or in
 Supplement combination with drugs with consider-
ably shorter half-lives (such as nucleo-
in their care. The guidelines now also in-
clude a table that summarizes the phar-
side analogue drugs [eg, zidovudine or macokinetic data and general concerns
lamivudine]). In the case of a nevirap- in pregnancy and makes recommenda-
ine-containing regimen, consideration tions about the suitability of each anti-
combination with other antiretroviral should be given to continuing the dual retroviral drug in pregnancy by catego-
drugs. Table 1 provides a summary of nucleoside analogue drug component of rizing each agent as (1) a recommended
recommendations for the treatment and the regimen for a period of time (ie, 3-7 agent, (2) an alternate agent, (3) insuffi-
prevention of mother-to-child HIV days) after discontinuation of nevirapine cient data to recommend use, and (4)
to reduce the risk of the development of not recommended. Although antiretro-
transmission for pregnant HIV-infected nevirapine resistance, although the opti- viral prophylaxis and treatment regi-
women in different clinical scenarios. mal duration of time to continue the mens have evolved rapidly and have be-
dual nucleosides is not known. come increasingly complicated, it is
After pregnancy, it is recommended interesting to note that zidovudine is still
that, if the woman does not meet criteria As noted earlier, highly active combi- the mainstay of perinatal prevention ef-
for treatment in nonpregnant women, nation therapy is now the norm for both forts, 10 years after the results of
consideration should be given to discon- nonpregnant and pregnant women, and PACTG protocol 076 were released. It is
tinuing therapy after delivery. In most because of the complex nature of the still recommended that zidovudine be
cases, all drugs should be stopped simul- management of HIV infection, it is rec- included in antiretroviral regimens for
taneously. One exception is when drugs ommended that a specialist with experi- pregnant women whenever possible.
with long half-lives (such as nonnucleo- ence in the treatment of pregnant
side drugs like nevirapine) are used in women with HIV infection be involved

Supplement to SEPTEMBER2009 American Journal of Obstetrics & Gynecology S29

 www.AJOG.org
Supplement
TABLE

Recommendations
HIV-infected womenforinantiretroviral drug use and prevention of mother to child HIV transmission in pregnant
the United States

Variable Recommendations

Clinical scenario
..................................................................................................................................................................................................................................................................................................................................................
..............................

HIV-1–infected woman of childbearing potential HAARTas per US treatment guidelines

but not pregnant who has indications for
the initiation of antiretroviral therapy Avoid drugs with teratogenic potential (eg, efavirenz) in women of child-
bearing age, unless adequate contraception ensured; exclude pregnancy

before starting treatment with efavirenz

..................................................................................................................................................................................................................................................................................................................................................
..............................

HIV-1–infected woman who receives HAART

and becomes pregnant

..........................................................................................................................................................................................................................................................................................................................................
.............................

Woman Continue current HAARTregimen; discontinue drugs with teratogenic potential

(eg, efavirenz) or with known adverse potential for the pregnant mother
(eg, combination stavudine [d4T] didanosine [ddI])

In general, if woman requires treatment, antiretroviral drugs should not be

stopped during the first trimester

If it is decided to discontinue antiretroviral drugs during the first trimester,

stop all drugs3 (if regimen includes drug with long half-life such as NNRTI,
consider stopping NRTIs 3-7 days after stopping NNRTIalthough limited
data exist)

Continue HAARTregimen during intrapartum (zidovudine given as continuous

infusion* during labor) and postpartum period

Elective cesarean delivery if plasma HIV-1 RNAremains 1000 copies/mL at

34-36 weeks of gestation
..........................................................................................................................................................................................................................................................................................................................................
.............................

Infant Zidovudine for 6 weeks

..................................................................................................................................................................................................................................................................................................................................................
..............................

HIV-1–infected pregnant woman with antenatal

plasma HIV-1 RNAof 1000 copies/mL

who does not currently receive

antiretroviral therapy
..........................................................................................................................................................................................................................................................................................................................................
.............................

Woman HAART(ideally contains zidovudine) consider delaying initiation until after the

first trimester

Because of risk of severe hepatic toxicity with nevirapine in women with CD4
of 250/mm , use nevirapine in this situation only if benefit clearly
outweighs risk and alternatives are not available

Continue HAARTregimen during intrapartum period (zidovudine given as

 continuous infusion* during labor)

Evaluate need for continued therapy after delivery; discontinue HAART,unless

there are indications for continued therapy (if regimen includes drug with
long half-life such as NNRTI,consider stopping NRTIs 3-7 days after
stopping NNRTI, although limited data exist)

Elective cesarean delivery if plasma HIV-1 RNAremains 1000 copies/mL at

34-36 weeks of gestation
..........................................................................................................................................................................................................................................................................................................................................
.............................

Infant Zidovudine for 6 weeks

..................................................................................................................................................................................................................................................................................................................................................
..............................

Clinical situation
..................................................................................................................................................................................................................................................................................................................................................
..............................

HIV-1–infected pregnant woman with antenatal

maternal plasma HIV-1 RNAof 1000

copies/mL who does not currently receive

antiretroviral therapy
..........................................................................................................................................................................................................................................................................................................................................
.............................

Woman Zidovudine given antepartum after the first trimester and as continuous

infusion* during labor

OR

HAART(ideally contains zidovudine) consider delaying initiation until after the

first trimester plus zidovudine given as continuous infusion* intrapartum;
discontinue HAARTafter delivery (if regimen includes drug with long half-
life such as NNRTI,consider stopping NRTIs 3-7 days after stopping
NNRTI,although limited data exists)
..........................................................................................................................................................................................................................................................................................................................................
.............................

Infant Zidovudine for 6 weeks

Continued on page S31.

S30 American Journal of Obstetrics & Gynecology Supplement to SEPTEMBER2009

www.AJOG.org
Supplement
TABLE

Recommendations
HIV-infected womenforinantiretroviral drug use and prevention of mother to child HIV transmission in pregnant
the United States

Continued from page S30.

Variable Recommendations

HIV-1–infected woman who has received no Several effective regimens are available to choose from:

antiretroviral therapy before labor (1) Woman: zidovudine given as continuous infusion* during labor; infant:
zidovudine for 6 weeks

OR

(2) Woman: zidovudine lamivudine every 12 hours during labor; infant:

zidovudine lamivudine for 1 week

OR

(3) Woman: single-dose nevirapine (Note: If delivery is imminent ( 1 hour), do

not give the maternal intrapartum nevirapine because of insufficient time
to reach adequate level in the infant; infant: single-dose nevirapine at 48-
72 hours of age (Note: If mother did not receive intrapartum nevirapine,
then give infant nevirapine at birth and 48-72 hours)

OR

(4) Combination zidovudine nevirapine: woman: zidovudine given as

continuous infusion* during labor, plus single-dose nevirapine at onset

labor; infant: single-dose nevirapine plus zidovudine for 6 weeks.

..................................................................................................................................................................................................................................................................................................................................................
..............................

Infant born to HIV-1–infected woman who has Zidovudine given for 6 weeks to the infant (started within 6-12 hours of birth)
received no antiretroviral therapy before OR
or during labor
Some clinicians may choose to use zidovudine in combination with additional
drugs, but appropriate dosing for neonates is defined incompletely and the
additional efficacy of this approach in reducing transmission is not known
..................................................................................................................................................................................................................................................................................................................................................
..............................
26
(Adaptedfrom Public Health Service TaskForce recommendationsfor use of antiretroviral drugs in pregnant HIV-1-infected womenfor maternal health and interventions to reduceperinatal HIV-1
transmission in the United States. Last accessed:October 23, 2006. Available at: http://AIDSInfo.nih.gov.)

HAART,highly active antiretroviral therapy; NRTI, nucleoside analogue reverse transcriptase inhibitor; NNRTI,nonnucleoside analogue reverse transcriptase inhibitor.

* Zidovudine continuous infusion: 2 mg/kg zidovudine intravenously over 1 hour followed by continuous infusion of 1 mg/kg/hr until delivery.
27
prophylaxis and for those women with ciated with resistance (eg, nonnucleoside
persistent viral replication while receiv-
ing antiretroviral treatment to optimize
Antiretroviral drug resistance is an- antiretroviral drug choice and to provide
other topic that has received consider- the most effective and durable regimen
able attention in the pregnancy guide- in women who need treatment and
lines in recent years, with sections greater preservation of future treatment
specifically addressing incidence, preva- options in women receive antiretroviral
lence, impact, management, and preven- prophylaxis. The development of resis-
tion of drug resistance in pregnancy and tance during pregnancy may have clini-
indications for and the significance of re- cal importance for both the pregnant
sistance testing. Resistance testing is rec- woman and her infant. The development
ommended for all pregnant women who of drug resistance is a problem for drugs
are not currently receiving antiretroviral for which a single mutation may be asso-
drugs before the initiation of therapy or
drugs such as nevirapine and efavirenz fetus to multiple drugs. However, the use
and lamivudine or emtricitabine), when of antiretroviral regimens that do not
the drug is used in the context of a non- fully suppress viral replication can be as-
suppressive antiretroviral regimen. In sociated with the development of resis-
contrast, for drugs in which multiple tance. Thus, current recommendations
mutations are required before resistance in the United States are for the use of
occurs (such as zidovudine), prolonged highly active combination therapy with
use as single-drug prophylaxis is gener-
ally required before resistance occurs; 3 drugs for pregnant women with on-
the development of zidovudine resis- going viral replication (HIV RNA,
tance was rare in PACTG 076. Because
1000 copies/mL) who do not require
the development of drug resistance is 1 of
therapy for their own health.
the major factors that leads to HIV ther-
apy failure, resistance that develops dur- In addition to summarizing informa-
ing pregnancy may have life-long impli- tion about antiretroviral drugs, the
cations for the woman. In addition, if the guidelines also include extensive discus-
woman transmits resistant virus to her sion of the preferred mode of delivery for
infant, future treatment options for the HIV-infected women. This expanded
infant may be limited. Because there are scope of the recommendations is re-
few drugs with adequate safety data in
flected in the current phrase, interven-
pregnancy, a general principle in obstet-
tions to reduce perinatal HIV-1 transmis-
rics is to minimize fetal exposure to
sion, which replaced the phrase
drugs. Therefore, early on, monotherapy
antiretroviral drugs in pregnant women in
and dual therapy were used extensively
the older title of the guidelines. In addi-
for prophylaxis in pregnant women with
tion to the 4 clinical scenarios that sum-
the aim of reducing the mother-to-child
marize the recommendations for use of
transmission risk without exposing the
antiretroviral drugs, the guidelines also
include 4 scenarios regarding the mode
of delivery. Other recent revisions to the

Supplement to SEPTEMBER2009 American Journal of Obstetrics & Gynecology S31

 13. Centers for Disease Control and Prevention.

Supplement HIV testing among pregnant women: United

States and Canada, 1998-2001. MMWR Morb

sey, California. MMWR Morb Mortal Wkly Rep

1982;31:665-7.
guidelines include an expanded section
2. Cowan MJ, Hellmann D, Chudwin D, Wara
on preconception counseling, which re- DW, Chang RS, Ammann AJ. Maternal trans-
fers to the CDC guidance on preconcep- mission of acquired immune deficiency syn-
tion counseling for all women and then drome. Pediatrics 1984;73:382-6.
addresses issues that are specific to HIV-
infected women. In addition, the new 3. Centers for Disease Control and Prevention.
Achievements in public health: reduction in peri-
guidelines summarize whatever preg-
natal transmission of HIV infection: United
nancy information is available for re- States, 1985-2005. MMWR Morb Mortal Wkly
cently approved antiretrovirals, such as Rep 2006;55:592-7.
tipranavir and darunavir.
4. Centers for Disease Control and Prevention.
Recommendations for assisting in the preven-
tion of perinatal transmission of human T-lym-
photropic virus type III/lymphadenopathy-asso-
C OMMENT ciated virus and acquired immunodeficiency
syndrome. MMWR Morb Mortal Wkly Rep
Throughout the HIV epidemic in the 1985;34:721-2.
United States, the Public Health Service
and its agencies such as the CDC and the 5. Barbacci MB, Dalabetta GA, Repke JT, et al.
National Institutes of Health have Human immunodeficiency virus infection in
women attending an inner-city prenatal clinic:
worked to translate rapidly the latest sci- ineffectiveness of targeted screening. Sex
entific findings into usable guidance for Transm Dis 1990;17:122-6.
clinicians on the frontline who take care
of HIV-infected patients. In the case of 6. Minkoff HL, Landesman SH. The case for
HIV screening of pregnant women, the routinely offering prenatal testing for human im-
munodeficiency virus. Am J Obstet Gynecol
autonomy of the woman must be bal- 1988;159:793-6.
anced against the benefits of identifying
HIV-infected pregnant women so that 7. Centers for Disease Control and Prevention.
preventive measures may be offered. In Recommendations of the US Public Health Ser-
addition, when prophylaxis and treat- vice Task Force on the use of zidovudine to
reduce perinatal transmission of human immu-
ment are administered to HIV-infected nodeficiency virus. MMWR Recomm Rep
pregnant women, the risks and benefits 1994;43:1-20.
to the woman must be balanced with
those of the infant. Although a great deal 8. Connor EM, Sperling RS, Gelber R, et al. Re-
of research in this area has resulted in duction of maternal-infant transmission of hu-
man immunodeficiency virus type 1 with zidovu-
dramatic progress, the prophylactic
18 and
dine treatment: Pediatric AIDS Clinical Trials
treatment regimens for HIV-infected Group Protocol 076 Study Group. N Engl J Med
pregnant women and their infants have 1994;331:1173-80.
become increasingly complex. Current
Public Health Service guidance regard- 9. Centers for Disease Control and Prevention.
US Public Health Service recommendations for
ing HIV screening of pregnant women
human immunodeficiency virus counseling and
has been published recently and up-to- voluntary testing for pregnant women. MMWR
date recommendations regarding pro- Recomm Rep 1995;44:1-15.
phylaxis and treatment are posted on the
internet (www.AIDSinfo.nih.gov) and 10. Institute of Medicine. Reducing the odds:
preventing perinatal transmission of HIV in the
are updated regularly. A major revision
United States. Washington, DC: National Acad-
to the prophylaxis and treatment guide- emy Press; 1999.
lines is anticipated in 2008. These HIV
screening and treatment guidelines are 11. Human immunodeficiency virus screening:
designed as a resource for clinicians and joint statement of the American Academy of Pe-
diatrics and the American College of Obstetri-
are recommendations only. Clinicians
cians and Gynecologists. Pediatrics 1999;
should be aware that they are subject to 104:128.
the laws and statutes in their states,
which may differ somewhat from these 12. Centers for Disease Control and Preven-
tion. Revised recommendations for HIV screen-
ing of pregnant women. MMWR Recomm Rep
2001;50:63-85.
 www.AJOG.org 19. Guay LA, Musoke P, Fleming T, et al. Intra- HIV-1 transmission in the United States: 7-6-
partum and neonatal single-dose nevirapine 2006 update. Last accessed: August 22, 2006.
compared with zidovudine for prevention of Available at: http://AIDSinfo.nih.gov.
mother-to-child transmission of HIV-1 in Kam-
pala, Uganda: HIVNET 012 randomised trial. 24. Centers for Disease Control and Preven-
Lancet 1999; 354:795-802. tion. Public Health Service Task Force recom-
of adults, adolescents, and pregnant women in mendations for the use of antiretroviral drugs in
health-care settings. MMWR Recomm Rep
20. Bulterys M, Jamieson DJ, O’Sullivan MJ, et pregnant women infected with HIV-1 for mater-
2006;55:1-17.
al. Rapid HIV-1 testing during labor: a multi- nal health and for reducing perinatal HIV-1
center study. JAMA 2004;292:219-23. transmission in the United States. MMWR
16. Sansom SL, Jamieson DJ, Farnham PG,
Recomm Rep 1998;47:1-30.
Bulterys M, Fowler MG. Human immunodefi-
21. American College of Obstetricians and Gy-
ciency virus retesting during pregnancy: costs
necologists. Prenatal and perinatal human im- 25. Department of Health and Human Services
and effectiveness in preventing perinatal trans-
munodeficiency virus testing: expanded recom- Panel on Antiretroviral Guidelines for Adults and
mission. Obstet Gynecol 2003;102:782-90.
mendations: ACOG committee opinion number Adolescents. Guidelines for the use of antiret-
17. Warren B, Glaros RHS. Residual perinatal
304. Obstet Gynecol 2004;104:1119-24. roviral agents in HIV-1-infected adults and ad-
HIV transmissions in 25 births occurring in New
olescents. Last accessed: October 23, 2006.
York state. Presentation at the 2005 National
22. Centers for Disease Control and Preven- Available at: http://AIDSinfo.nih.gov.
HIV Prevention Conference, Atlanta, GA; 2005.
tion. Zidovudine for the prevention of HIV trans-
18. Branson BM, Handsfield HH, Lampe MA, et
mission from mother to infant. MMWR Morb 26. Eastman PS, Shapiro DE, Coombs RW, et
al for the Centers for Disease Control and Pre-
Mortal Wkly Rep 1994;43:285-7. al. Maternal viral genotypic zidovudine resis-
vention. Revised recommendations for HIV
tance and infrequent failure of zidovudine ther-
testing of adults, adolescents, and pregnant
23. Public Health Service Task Force. Recom- apy to prevent perinatal transmission of human
women in health care settings. MMWR Morb
mendations for use of antiretroviral drugs in
Mortal Wkly Rep 2006;55:1-17.
pregnant HIV-1 infected women for maternal
health and interventions to reduce perinatal
federal guidelines. f Mortal Wkly Rep 2002;51:1013-6. immunodeficiency virus type 1 in pediatric AIDS
Clinical Trials Group protocol 076. J Infect Dis
14. Gerberding JL, Jaffe HW. ”Dear Colleague” 1998;177:557-64.
letter, April 22, 2003. Last accessed: July 29,

REFERENCES 2006. Available at: http://www.cdc.gov/hiv/ 27. Jamieson DJ, Read J, Kourtis AP, Durant
TM, Lampe M, Dominguez K. Cesarean delivery
1. Centers for Disease Control and Prevention. projects/perinatal/2003/letter.htm .
for HIV-infected women: Recommendations
Unexplained immunodeficiency and opportu- and controversies. Am J Obstet Gynecol 2006.
nistic infections in infants: New York, New Jer- 15. Centers for Disease Control and Preven-
tion. Revised recommendations for HIV testing

S32 American Journal of Obstetrics & Gynecology Supplement to SEPTEMBER2009