Transcript AIDS Education and Training Center National Coordinating Resource Center Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions.

AIDS Education and Training Center
National Coordinating Resource Center
Recommendations for Use of Antiretroviral Drugs in
Pregnant HIV-1-Infected Women for Maternal Health and
Interventions to Reduce Perinatal HIV Transmission
in the United States
HHS Panel on the Treatment of HIV-infected Pregnant Women and
Prevention of Perinatal Transmission
A Working Group of the Office of AIDS Research Advisory Council
AETC NCRC Slide Set
About This Presentation
 These slides were developed from the August 6, 2015
revisions to the guidelines.
 The goal of the guidelines is to provide guidance to HIV
care practitioners. Because the field of HIV care is
changing rapidly, users of this slide set are advised to
check http://aidsinfo.nih.gov/guidelines/html/3/perinatalguidelines/0 for updates.
 It is intended that these slides be used as prepared,
without changes in either content or attribution. Users are
asked to honor this intent.
 AETC National Coordinating Resource Center
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August 2015
Table of Contents
Topic







3
Introduction
Preconception Counseling
Antepartum Care
Intrapartum Care
Postpartum Care
Care of the Neonate
Appendices
Slide Number
6
9
27
112
122
128
151
August 2015
Abbreviations

Antibody (Ab)

Antigen (Ag)

Antiretroviral (ARV)

Antiretroviral therapy (ART) Centers for Disease Control and Prevention (CDC)

Combination antiretroviral therapy (cART)

Enzyme immunoassay (EIA)

Fixed dose combination (FDC)

Immune reconstitution inflammatory syndrome (IRIS)

Integrase strand transfer inhibitor (INSTI)

Intrauterine device (IUD)

Nucleoside/Nucleotide analogue reverse transcriptase inhibitor (NRTI/NtRTI)

Non-Nucleoside analogue reverse transcriptase inhibitor (NNRTI)

Pharmacokinetic (PK)

Polymerase chain reaction (PCR)

Proton pump inhibitor (PPI)

Pre-exposure prophylaxis (PrEP)

Protease inhibitor (PI)

Viral load (VL)
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August 2015
Drug Abbreviations
NRTI
Abacavir (ABC)
Didanosine (ddI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Tenofovir DF (TDF)
Zidovudine (AZT, ZDV)
PI
Atazanavir (ATV)
Darunavir (DRV)
Fosamprenavir (FPV)
Indinavir (IDV)
Lopinavir (LPV)
Nelfinavir (NFV)
Saquinavir (SQV)
Tipranavir (TPV)
Entry Inhibitor
Enfuvirtide (ENF, T-20)
Maraviroc (MVC)
INSTI
Raltegravir (RAL)
Elvitegravir (EVG)
Dolutegravir (DTG)
NNRTI
Efavirenz (EFV)
Etravirine (ETR)
Nevirapine (NVP)
Rilpivirine (RPV)
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Pharmacokinetic
Enhancers
Ritonavir (RTV, /r)
Cobicistat (COBI)
August 2015
Introduction (1)
 With universal prenatal HIV counseling and testing,
preconception care, ARV prophylaxis, scheduled Csection delivery (if indicated), and avoidance of breastfeeding, the rate of perinatal transmission of HIV infection
has diminished to <2% in the United States.
 The CDC goal for elimination of perinatal HIV transmission
in the U.S. is defined as a rate of <1%.
 A focus on appropriate overall medical care for HIVinfected women is the best way to prevent HIV infection
of infants.
 Every HIV-infected infant is a sentinel event representing
missed opportunities for prevention.
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August 2015
Introduction (2)
 A critical component of prevention of perinatal HIV
transmission is ensuring the use of ART to maximally
suppress viral replication as early as possible during
pregnancy.
 Combined antepartum, intrapartum, and infant ARV
prophylaxis is recommended to prevent perinatal
transmission of HIV.
 ARV drugs reduce perinatal transmission by several
mechanisms, including:
 Lowering maternal antepartum HIV RNA (viral load).
 Providing infant pre- and post-exposure prophylaxis.
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August 2015
Introduction (3)
Recommendations in these guidelines are based on
scientific evidence and expert opinion and are rated using
the system below:
Strength of
Recommendation
A: Strong
B: Moderate
C: Optional
Quality of Evidence
I: One or more randomized trials with
clinical outcomes and/or validated
laboratory end points
II: One or more well-designed,
nonrandomized trials or observational
studies with long-term clinical outcomes
III: Expert opinion
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August 2015
AIDS Education and Training Center
National Coordinating Resource Center
PRECONCEPTION
COUNSELING AND CARE FOR
HIV-INFECTED WOMEN OF
CHILDBEARING AGE
Preconception Counseling and Care (1)
 Comprehensive family planning and
preconception care is part of routine primary
care and is recommended by CDC, ACOG,
and other national organizations.
 Purpose:
 Prevention of unintended pregnancies.
 Optimization of maternal health prior to
pregnancy.
 Prevention of perinatal transmission.
 Prevention of HIV transmission to an
uninfected partner while trying to conceive.
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August 2015
Preconception Counseling and Care (2)
Recommendations
 Discuss childbearing intentions with all women of
childbearing age on an ongoing basis throughout
the course of their care (AIII).
 Provide information about effective and appropriate
contraceptive methods to reduce the likelihood of
unintended pregnancy (AI).
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August 2015
Preconception Counseling and Care (3)
 During preconception counseling, include information
on safer sexual practices and elimination of alcohol,
illicit drugs, and smoking (AII).
 All HIV-infected women contemplating pregnancy
should be receiving combination antiretroviral therapy
(cART) and have a plasma viral load below the limit
of detection prior to conception (AII).
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August 2015
Preconception Counseling and Care (4)
 When selecting or evaluating cART for HIVinfected women of childbearing age, consider the
following (AII):
 A regimen’s effectiveness.
 A woman’s hepatitis B status.
 Teratogenic potential of the drugs in the cART
regimen.
 Possible adverse outcomes for the mother and
fetus.
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August 2015
Preconception Counseling and Care (5)
 Women who do not desire pregnancy should be offered
contraception, including hormonal contraception and
intrauterine devices.
 HIV infection does not preclude the use of any
contraceptive method (AII). However, drug-drug
interactions between hormonal contraceptives and
cART should be taken into account.
 Interactions between some ARVs and hormonal
contraceptives may lower contraceptive efficacy.
 Emergency contraception can be used as appropriate ̶
either pills or copper IUD.
 Again, be aware of potential interactions with ARVs that could
lower contraceptive efficacy.
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August 2015
Drug Interactions between ARVs and Hormonal
Contraceptives (CIII (1)
NNRTIs: See Guidelines Table 3
ARV
Drug
Recommendation for
Combined Hormonal
Methods and
Progestin-Only Pills
Recommendation
for DMPA
Recommendation for
Etonogestrel Implants
EFV
Use alternative or
additional contraception
No additional
contraceptive needed
Use alternative or
additional contraception
ETR
No additional
contraceptive needed
No additional
contraceptive needed
No additional
contraceptive needed
NVP
Consider alternative
contraceptive, or barrier
+ oral hormonal methods
No additional
contraceptive needed
Consider alternative
contraceptive, or
barrier + implant
RPV
No additional
contraceptive needed
No additional
contraceptive needed
No additional
contraceptive needed
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August 2015
Drug Interactions between ARVs and Hormonal
Contraceptives (CIII) (2)
RTV-Boosted PIs: See Guidelines Table 3
ARV
Drug
Recommendation for
Combined Hormonal
Methods and
Progestin-Only Pills
Recommendation for
DMPA
Recommendation
for Etonogestrel
Implants
ATV/r
Use alternative or
additional contraception
No additional
contraceptive needed
Consider alternative
contraceptive, or
barrier + implant
DRV/r
Use alternative or
additional contraception
No additional
contraceptive needed
No additional
contraceptive needed
FPV/r
Use alternative or
additional contraception
No additional
contraceptive needed
Consider alternative
contraceptive, or
barrier + implant
LPV/r
Use alternative or
additional contraception
No additional
contraceptive needed
Consider alternative
contraceptive, or
barrier + implant
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August 2015
Drug Interactions between ARVs and Hormonal
Contraceptives (CIII) (3)
RTV-Boosted PIs: See Guidelines Table 3
ARV
Drug
Recommendation for
Combined Hormonal
Methods and ProgestinOnly Pills
Recommendation for
DMPA
Recommendation for
Etonogestrel Implants
SQV/r
Use alternative or
additional contraception
No additional
contraceptive needed
Consider alternative
contraceptive, or barrier +
implant
TPV/r
Use alternative or
additional contraception
No additional
contraceptive needed
Consider alternative
contraceptive, or barrier +
implant
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August 2015
Drug Interactions between ARVs and Hormonal
Contraceptives (CIII) (4)
PIs without RTV: See Guidelines Table 3
ARV
Drug
ATV
Recommendation for Combined
Hormonal Methods and ProgestinOnly Pills
Recommendation
for DMPA
Recommendation
for Etonogestrel
Implants
No additional contraceptive needed
No additional
contraceptive
needed
No additional
contraceptive
needed
No additional
contraceptive
needed
Use alternative or
additional
contraception
•OC should contain ≤30 μg ethinyl
estradiol (EE), or use alternative method
•No data on OCs with <25 μg EE or
progestins other than norethindrone or
norgestimate
FPV
Use alternative contraception
(use with estradiol/norethindrone may
cause virologic failure)
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August 2015
Drug Interactions between ARVs and Hormonal
Contraceptives (CIII) (5)
PIs without RTV: See Guidelines Table 3
ARV
Drug
Recommendation for
Combined Hormonal
Methods and Progestin-Only
Pills
Recommendation
for DMPA
Recommendation
for Etonogestrel
Implants
IDV
No additional contraceptive
needed
No additional
No additional
contraceptive needed contraceptive needed
NFV
Use alternative or additional
contraception
No additional
Use alternative or
contraceptive needed additional
contraception
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August 2015
Drug Interactions between ARVs and Hormonal
Contraceptives (CIII) (6)
Integrase Inhibitors: See Guidelines Table 3
ARV Drug
Recommendation for
Combined Hormonal
Methods and
Progestin-Only Pills
Recommendation for
DMPA
Recommendation for
Etonogestrel Implants
RAL
DTG
No additional
contraceptive needed
No additional
contraceptive needed
No additional
contraceptive needed
EVG/COBI
CCR5 Antagonist: See Guidelines Table 3
ARV
Drug
MVC
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Recommendation for
Combined Hormonal
Methods and
Progestin-Only Pills
Recommendation for
DMPA
Recommendation for
Etonogestrel Implants
No additional contraceptive needed
August 2015
Reproductive Options for HIV-Concordant and
Serodiscordant Couples (1)
For concordant (both partners are HIV infected)
and discordant couples:
 Expert consultation is recommended so that approaches
can be tailored to specific needs (AIII).
 Partners should be screened and treated for genital tract
infections before attempting to conceive (AII).
 The HIV-infected partner should attain maximum viral
suppression before attempting conception (AIII).
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August 2015
Reproductive Options for HIV-Concordant
and Serodiscordant Couples (2)
For discordant couples:
The HIV-infected partner should be receiving combination
antiretroviral therapy and demonstrate sustained suppression
of plasma viral load below the limits of detection (AI).
 cART for the infected partner may not be fully protective
against sexual transmission of HIV.
Periconception administration of antiretroviral preexposure
prophylaxis (PrEP) for HIV-uninfected partners may offer an
additional tool to reduce the risk of sexual transmission. (CIII)
The utility of PrEP for the uninfected partner when the infected
partner is receiving cART and has a suppressed viral load has
not been studied.
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August 2015
Reproductive Options for HIV-Concordant
and Serodiscordant Couples (3)
Discordant couples with HIV-infected women:
The safest conception option is artificial insemination,
including the option of self-insemination with a
partner’s sperm during the periovulatory period (AIII).
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August 2015
Reproductive Options for HIV-Concordant
and Serodiscordant Couples (4)
Discordant couples with HIV-infected men:
 The use of donor sperm from an HIV-uninfected male with
artificial insemination is the safest option (AIII).
 When the use of donor sperm is unacceptable, the use of
sperm preparation techniques coupled with either
intrauterine insemination or in vitro fertilization should be
considered (AII).
 Semen analysis is recommended for HIV-infected males
before conception is attempted to prevent unnecessary
exposure to infectious genital fluid when the likelihood of
getting pregnant is low because of semen abnormalities
(AIII).
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August 2015
Reproductive Options for HIV-Concordant
and Serodiscordant Couples (5)
 Periconception PrEP
 Very few data to date on periconception PrEP; studies
under way.
 Infected partner should be on ART with fully suppressed
HIV viral load.
 Once daily tenofovir/emtricitabine is currently FDA
approved for PrEP; CDC recommends 1 month before and
1 month after conception attempted.
 Couples should use condoms at all times except during
periovulatory intercourse.
 No reported increase in congenital anomalies for children
whose mothers were exposed to tenofovir or emtricitabine
during first trimester.
Review Table 4 “Clinical Trials of PrEP” for more information
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August 2015
Reproductive Options for HIV-Concordant
and Serodiscordant Couples (6)
 Baseline laboratory testing for HIV infection,
renal function, pregnancy, and chronic HBV
infection should be done before initiating PrEP.
 HBV-uninfected individuals should be vaccinated.
 Monitor for potential side effects such as renal
dysfunction and clinical toxicities.
 Conduct pregnancy test every 3 months.
 Test HIV-uninfected partner for HIV every 3 months; if
result is HIV positive, discontinue PrEP to minimize
drug resistance and refer for treatment.
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August 2015
AIDS Education and Training Center
National Coordinating Resource Center
ANTEPARTUM CARE
Principles of ARV Use during Pregnancy (1)
 Initial evaluation of HIV-infected pregnant women should
include assessment of HIV disease status and
recommendations regarding initiation or modification of
cART (AIII).
 All pregnant women should receive ART to prevent perinatal
transmission regardless of HIV RNA and CD4 levels (AI).
The goal of cART is to maintain a viral load below the limit of
detection throughout pregnancy.
 Combined antepartum, intrapartum, and infant ARV
prophylaxis is recommended because ARV drugs reduce
perinatal transmission by several mechanisms, including
lowering maternal antepartum viral load and providing infant
pre- and postexposure prophylaxis (AI).
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August 2015
Principles of ARV Use during Pregnancy (2)
 The known benefits and potential risks of all medication use,
including ARV use, during pregnancy should be discussed
with all HIV-infected women (AIII).
 The importance of adherence to ARV regimens should be
emphasized in patient counseling (AII).
 ARV drug-resistance studies should be performed before
starting or modifying ARV drug regimens in women whose
HIV RNA is above the threshold for resistance testing (AIII).
 In pregnant women not already receiving cART, consideration
should be given to initiating cART before results of drugresistance testing are available because earlier viral
suppression has been associated with lower risk of
transmission. If cART is initiated before results are available,
the regimen should be modified, if necessary, based on
resistance assay results (BIII).
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August 2015
Principles of ARV Use during Pregnancy (3)
 Coordination of services among prenatal care
providers, primary care and HIV specialty
care providers, and when appropriate, mental
health and drug abuse treatment services,
and public assistance programs, is essential
to ensure that infected women adhere to their
ARV drug regimens (AIII).
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August 2015
Clinician Consultation Center
(formerly the National Perinatal HIV Hotline)
(1-888-448-8765)
http://nccc.ucsf.edu/clinician-consultation/perinatal-hiv-aids/
For free clinical consultation about all aspects of
perinatal HIV care
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August 2015
General Principles of Drug Selection
 Guidelines for use of cART for maternal health during pregnancy
generally are the same as for women who are not pregnant.
 Some modifications based on concerns about specific ARVs during
pregnancy and limited experience during pregnancy with newer ARVs.
 Consider and discuss the benefits vs. risks of ARV drug use during
pregnancy.
 Ensure that at least 1 NRTI with high placental transfer is included in
cART regimen for sufficient infant preexposure prophylaxis.
 Counsel women on the importance of close adherence to ARV
regimen.
 Offer support services, mental health services, smoking cessation,
and drug abuse treatment plans as indicated.
 Coordinate between HIV and OB specialists.
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August 2015
Teratogenicity (1)
 All cases of ARV drug exposure during pregnancy should
be reported to the Antiretroviral Pregnancy Registry at:
http://www.APRegistry.com (AIII).
 Efavirenz (EFV):
 Nonpregnant women of childbearing potential should
undergo pregnancy testing before initiation of EFV and
receive counseling about the potential risk to the fetus and
desirability of avoiding pregnancy while on EFV-containing
regimens (AIII).
 Alternative ARV regimens that do not include EFV should be
strongly considered in women who are planning to become pregnant
or are sexually active and not using effective contraception,
assuming these alternative regimens are not thought to compromise
the woman’s health (BIII).
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August 2015
Teratogenicity (2)
 EFV can be continued in women receiving an EFV-based
regimen who present for antenatal care in the first trimester
because the risk of neural tube defects is restricted to the
first 5-6 weeks of pregnancy. Pregnancy is rarely
recognized before 5-6 weeks of pregnancy, and
unnecessary changes in ARV drugs during pregnancy may
be associated with loss of viral control and increased risk of
perinatal transmission. In such situations, fetal ultrasound
is recommended at 18 to 20 weeks to assess anatomy
(CIII).
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August 2015
Teratogenicity (3)
 Data from recently-reported cohort studies and updated
APR data reaffirm the lack of association between first
trimester exposure to any ARV’s and increased risk of
birth defects.
 A recent study found small but statistically significant
decreases in bone mineral content in newborns exposed
to tenofovir in utero. Clinical significance and long term
outcome not clear.
 Refer to Table 7 and Appendix B for information about
individual drugs.
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August 2015
Combination ARV Drug Regimens and
Pregnancy Outcome
 Clinicians should be aware of a possible
small increased risk of preterm birth in
pregnant women receiving protease inhibitor
(PI)-based ART. However, given the clear
benefits of such regimens for both a
women’s health and prevention of perinatal
transmission, PIs should not be withheld for
fear of altering pregnancy outcome (AII).
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August 2015
Recommendations for Use of ARVs during
Pregnancy (1)
 In general, the same regimens as recommended for treatment of
nonpregnant adults should be used in pregnant women unless there are
known adverse effects for women, fetuses, or infants that outweigh
benefits (AIII).
 Multiple factors must be considered when choosing a regimen for a
pregnant woman including comorbidities, convenience, adverse effects,
drug interactions, resistance testing results, pharmacokinetics (PK), and
experience with use in pregnancy (AII).
 PK changes may lead to lower plasma drug levels of drugs and
necessitate increased dosages, more frequent dosing, or boosting,
especially of protease inhibitors (AII).
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August 2015
Recommendations for Use of ARVs during
Pregnancy (2)
 Individualize ARVs based on factors such as:






38
Potential adverse effects on woman and on fetus
Experience in pregnancy
Genotypic resistance testing and prior ARV exposure
PK changes in pregnancy, placental ARV transfer
Comorbidities
Ability to adhere and convenience
August 2015
ART for Pregnant Women Who Are ARV Naive (1)
 All HIV-infected pregnant women should receive
cART to reduce the risk of perinatal transmission of
HIV (AI).
 The choice of regimen should take into account current
adult treatment guidelines, what is known about the use
of specific drugs in pregnancy, and the risk of
teratogenicity (see Tables 6 and 7 for drug information).
 Reducing HIV RNA to undetectable levels lowers the risk
of perinatal transmission, lessens the need for elective Csection to reduce risk of HIV transmission, and reduces
risk of ARV drug resistance in the mother.
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August 2015
ART for Pregnant Women Who Are ARV Naive (2)
 Consideration should be given to initiating cART as
soon as HIV is diagnosed during pregnancy; earlier
viral suppression is associated with lower risk of
transmission. This decision may be influenced by
CD4 count, HIV RNA levels, and maternal conditions
(e.g., nausea and vomiting) (AIII). The benefits of
cART must be weighed against potential fetal effects
of drug exposure.
 Fetuses are most susceptible to potential teratogenic effects in
the first trimester. However, evidence from observational
studies has been reassuring showing no differences in rates of
birth defects between first trimester and later gestational
exposures or rates in the general population.
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August 2015
ART for Pregnant Women Who Are ARV Naive (3)
 ARV drug-resistance studies should be
performed to guide selection of ARV regimen in
women whose HIV RNA is above the threshold
for resistance testing unless drug-resistance
studies have already been performed (AI).
 If cART is initiated before the results of the drugresistance assays are available, the antiretroviral
regimen should be modified, if necessary, based
on the resistance assay results (BIII).
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August 2015
ART for Pregnant Women Who Are ARV Naive (4)
 cART regimens for ARV naïve pregnant women should
include at least 3 ARVs, as in nonpregnant adults:
 2 NRTIs + 1 ritonavir-boosted PI OR 2 NRTIs + 1 NNRTI, OR 2
NRTIs + 1 integrase inhibitor.
 If there is no evidence of resistance, preferred cART
regimens for the treatment of antiretroviral-naive HIVinfected pregnant women include:
 a dual NRTI combination (ABC/3TC, TDF/FTC or 3TC, or
ZDV/3TC) AND either a ritonavir-boosted PI (ATV/r or DRV/r),
OR a NNRTI (EFV initiated after 8 weeks of pregnancy), OR an
integrase inhibitor (RAL) (AIII).
See Table 6 for information about ARV regimens for ARV naïve pregnant
women: Preferred, Alternative, Insufficient data and Not recommended
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August 2015
ART for Pregnant Women Who Are ARV Naive (5)
 Preferred Drugs or Drug Combinations
 Clinical trial data in adults have demonstrated
optimal efficacy and durability with
acceptable toxicity and ease of use.
 Pregnancy-specific PK data are available to
guide dosing.
 No established association with teratogenic
effects or clinically significant adverse
outcomes for mothers, fetuses, or newborns.
 Some recommended ARVs may have toxicity in
animal studies that has not been verified in
humans.
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August 2015
Initial ART for ARV-Naive Pregnant Women (1)
Preferred 2-NRTI Backbone Regimens
Comments
ABC/3TC
• Available as FDC, can be given once daily
• Potential HSR: ABC should not be used in
patients who test positive for HLA-B*5701
because of risk of hypersensitivity reaction
• Not recommended with ATV/r or with EFV if
pretreatment HIV RNA >100,000 copies/mL
TDF/FTC or TDF +
3TC
• Available as FDC, can be given once daily
• TDF has potential renal toxicity, use with caution
in patients with renal insufficiency
ZDV/3TC
• Most experience for use during pregnancy
• Available as FDC. Twice-daily administration
• Higher risk of hematologic toxicity
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August 2015
Initial ART for ARV-Naive Pregnant Women (2)
Preferred PI Regimens
Comments
ATV/r + preferred 2-NRTI • Once daily administration
• Extensive experience in pregnancy
backbone
• Maternal hyperbilirubinemia
DRV/r + preferred 2-NRTI • Better tolerated than LPV/r.
• PK data available. Increasing
backbone
experience in pregnancy
• Must be used twice-daily in
pregnancy.
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August 2015
Initial ART for ARV-Naive Pregnant Women (3)
Preferred NNRTI Regimen
Comments
EFV + preferred 2-NRTI
backbone
Note:
May be initiated after the first 8 weeks
of pregnancy
46
• Birth defects in primates; risk in
humans is unclear.
• Postpartum contraception must
be ensured.
• Preferred regimen in women
requiring coadministration of
drugs with significant
interactions with PIs or the
convenience of co-formulated,
single-tablet, once-daily
regimen.
August 2015
Initial ART for ARV-Naive Pregnant Women (3)
Preferred Integrase Inhibitor Regimen
Comments
RAL + preferred 2-NRTI
backbone
47
• PK data available and
increasing experience in
pregnancy.
• Rapid viral load reduction.
• Useful when drug interactions
with PI regimens are a concern.
• Twice-daily dosing required.
August 2015
Initial ART for ARV-Naive Pregnant Women (4)
Alternative Regimens:
Clinical trial data demonstrate efficacy in adults
but experience in pregnancy is limited, data are
lacking or incomplete on teratogenicity, or the
drug or regimen is associated with dosing,
tolerability, formulation, toxicity, or interaction
issues.
48
August 2015
Initial ART for ARV-Naive Pregnant Women (5)
Alternative PI Regimens
Comments
LPV/r + preferred 2NRTI backbone
49
• Abundant experience and established
PK in pregnancy.
• More nausea than preferred agents.
• Twice-daily administration. Once-daily
LPV/r is not recommended for use in
pregnant women.
August 2015
Initial ART for ARV-Naive Pregnant Women (6)
Alternative NNRTI Regimen
Comments
RPV + preferred 2NRTI backbone
50
• RPV not recommended with pretreatment HIV RNA >100,000 copies/mL or
CD4 cell count <200 cells/mm3.
• Do not use with PPIs.
• PK data available in pregnancy but
relatively little experience with use in
pregnancy.
• Available in co-formulated single-pill
once daily regimen.
August 2015
Initial ART for ARV-Naive Pregnant Women (7)
Insufficient Data to Recommend:
Drugs and drug combinations are approved for use
but lack sufficient pregnancy-specific PK or safety
data.
Not Recommended:
Inferior virologic response, potentially serious
maternal or fetal safety concerns, or
pharmacologic antagonism, or not recommended
for ARV-naive non-pregnant populations.
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August 2015
Initial ART for ARV-Naive Pregnant Women (8)
Insufficient Data to Recommend Routine Use
DTG
EVG/COBI/TDF/FTC FDC
FPV
MVC
RPV
Not Recommended
ABC/3TC/ZDV
SQV
d4T
ETR
ddI
NVP
IDV/r
T-20
NFV
TPV/r
RTV as single PI
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August 2015
Table 7. Antiretroviral Drug Use in Pregnant HIVInfected Women
 Summary table of information about individual
ARVs with pharmacokinetic and toxicity data and
recommendations for use in pregnancy. Includes:
 Formulations, including fixed dose combinations
(FDCs)
 Dosing recommendations
 Pharmacokinetics
 Dosing in pregnancy
 Use in pregnancy




53
Placental transfer
Teratogenicity
Toxicity
Considerations about use
August 2015
Individual ARVs: Nucleoside and Nucleotide
Reverse Transcriptase Inhibitors (1)
Comments on Use during Pregnancy
Abacavir
(ABC)
PK not significantly altered. High placental transfer. No evidence
of teratogenicity.
Hypersensitivity reactions occur in 5-8% of nonpregnant
women; much smaller percentage are fatal and usually
associated with rechallenge. Testing for HLA-B*5701 identifies
patients at risk; conduct before starting ABC, do not give if
positive.
Didanosine PK not significantly altered. Low-moderate placental transfer.
(ddl)
Do not use with d4T; may cause lactic acidosis and death if
used together.
Increased rate of birth defects compared with general population
noted after 1st trimester and later exposure, relevance uncertain.
54
August 2015
Nucleoside and Nucleotide Reverse
Transcriptase Inhibitors (2)
Comments on Use during Pregnancy
Emtricitabine PK not significantly altered. High placental transfer. No
evidence of teratogenicity.
(FTC)
Active against HBV; if hepatitis B (HBV)-coinfected, flare
may occur if drug stopped.
Lamivudine
(3TC)
PK not significantly altered. High placental transfer. No
evidence of teratogenicity.
Active against HBV; if HBV-coinfected, flare may occur if
drug stopped.
Stavudine
(d4T)
PK not significantly altered. High placental transfer. No
evidence of teratogenicity.
Do not use with ddl or ZDV. May cause lactic acidosis
or death if ddI and d4T used together.
August 2015
55
Nucleoside and Nucleotide Reverse
Transcriptase Inhibitors (3)
Comments on Use during Pregnancy
Tenofovir
Disoproxil
Fumarate
(TDF)
AUC lower in 3rd trimester; trough levels adequate—no
dosing change needed. High placental transfer. No
evidence of human teratogenicity.
In monkeys, decreased fetal growth and fetal bone
porosity. Human studies demonstrate no effect on
intrauterine growth, but data are conflicting about potential
effects on growth outcomes later in infancy.
Risk of renal toxicity; monitor renal function.
Active against HBV; if HBV-coinfected, hepatitis flare may
occur if drug stopped.
Zidovudine
(AZT, ZDV)
56
PK not significantly altered. High placental transfer. No
evidence of teratogenicity.
August 2015
Table 7. Nonnucleoside Reverse
Transcriptase Inhibitors (NNRTIs) (1)
Comments on Use during Pregnancy
Efavirenz
(EFV)
AUC decreased in 3rd trimester but no change in dose
indicated. Moderate placental transfer.
Potential fetal safety concern. CNS or other malformations
observed in 3 of 20 monkeys; 6 human reports + 1 case report
of CNS defects and 1 report of anophthalmia.
• Counsel nonpregnant women on risks and conduct
pregnancy test prior to initiation of EFV.
• Consider alternative regimen in women planning to become
pregnant and those who are sexually active and not using
effective contraception, assuming alternatives are
acceptable to provider and will not compromise health of the
woman.
• Continue EFV in pregnant women receiving and EFV-based
regimen who present for care in 1st trimester if there is
virologic suppression on the regimen.
57
August 2015
Nonnucleoside Reverse Transcriptase
Inhibitors (NNRTIs) (2)
Comments on Use during Pregnancy
Etravirine
(ETR)
PK data suggest increased exposure, no dosing change
needed. Variable placental transfer—usually moderate to
high. Teratogenicity data insufficient in humans; no evidence
of teratogenicity in rats or rabbits.
Nevirapine PK not significantly altered. High placental transfer. No
evidence of teratogenicity.
(NVP)
Increased risk of potentially life-threatening hepatotoxicity
(often rash-associated) in women with high CD4 count at the
time of NVP initiation. If CD4 is >250 cells/µL, start NVP only
if benefit outweighs risk. Elevated transaminase levels at
baseline may also increase risk. Women who become
pregnant while on NVP and are tolerating it well can continue,
regardless of CD4 count.
58
August 2015
Non-nucleoside Reverse Transcriptase
Inhibitors (NNRTIs) (3)
Comments on Use during Pregnancy
Rilpivirine
(RPV)
59
Reduced PK but exceeded target exposure, no dosing
change needed. Moderate to high placental transfer.
Insufficient data to assess for teratogenicity in
humans. No evidence of teratogenicity in rats or
rabbits.
August 2015
Protease Inhibitors (1)
Class concerns for PIs: hyperglycemia, diabetes mellitus, diabetic
ketoacidosis, question of increased risk of preterm delivery
Recommendations for Use during Pregnancy
Atazanavir
(ATV)
Decreased ATV plasma concentrations during pregnancy; further
reduced further when given concomitantly with TDF or H2receptor antagonist. Low placental transfer. No evidence of
human teratogenicity.
Must be given with RTV boosting during pregnancy, unboosted
ATV not recommended. Use of ATV/r with TDF AND H2
antagonist in pregnancy not recommended.
Unknown effect of in utero ATV exposure on infant indirect
bilirubin levels; nonpathologic elevations of hyperbilirubinemia
observed in some neonates.
60
August 2015
Protease Inhibitors (2)
Comments on Use during Pregnancy
Darunavir
(DRV)
Decreased exposure in pregnancy. Once daily dosing not
recommended, give twice daily. Increased twice daily
DRV dose being investigated. Low placental transfer. No
evidence of human teratogenicity.
Must be combined with low-dose RTV.
Fosamprenavir AUC reduced during 3rd trimester. Low placental transfer.
Insufficient data to assess teratogenicity risk in humans;
(FPV)
increased fetal loss in rabbits; no increase in defects in
rats and rabbits.
Give twice daily standard dose with RTV boosting during
pregnancy. Unboosted FPV or once daily FOS with RTV
boosting not recommended.
61
August 2015
Protease Inhibitors (3)
Comments on Use during Pregnancy
Indinavir
(IDV)
Minimal placental transfer. No evidence of human teratogenicity
in cases reported to APR.
Must be given with RTV boosting during pregnancy. Unboosted
IDV not recommended.
Theoretical concern regarding increased bilirubin in neonates.
Lopinavir/
ritonavir
(LPV/r)
PK indicated reduced exposure during pregnancy. Low placental
transfer. No evidence of human teratogenicity.
Must be given twice daily during pregnancy. Some experts
recommend dosage increase in 2nd and 3rd trimesters. Monitor
virologic response and LPV drug levels with standard dose.
Oral solution contains 42% alcohol and 15% propylene glycol
and is not recommended for use during pregnancy.
62
August 2015
Protease Inhibitors (4)
Comments on Use during Pregnancy
Nelfinavir Lower NFV exposure in 3rd trimester. Twice daily dosing.
Minimal to low placental transfer. No evidence of human
(NFV)
teratogenicity.
Contains aspartame, should not be used in individuals with
phenylketonuria.
Ritonavir Recommended only as low dose PK booster for other PIs. See
pharmacokinetic enhancers.
(RTV)
63
August 2015
Protease Inhibitors (5)
Comments on Use during Pregnancy
Saquinavir
(SQV)
SQV exposure may be reduced in pregnancy but not
significantly. No dose change needed. Low placental transfer.
Insufficient data to assess for teratogenicity in humans; no
evidence of teratogenicity in rats or rabbits.
Must be combined with low-dose RTV boosting.
PR and/or QT interval prolongations have been observed;
baseline ECG recommended before starting. Contraindicated if
cardiac conduction system disease. SQV contraindicated in
patients with preexisting cardiac conduction system disease.
Tipranavir
(TPV)
64
No PK data in human pregnancy. Moderate placental transfer
reported in 1 patient.
Insufficient data to assess for teratogenicity in humans; no
evidence of teratogenicity in rats or rabbits.
August 2015
Entry Inhibitors
Comments on Use during Pregnancy
Enfurvirtide
(T-20)
No PK data in pregnancy. Minimal/low placental
transfer. No data on human teratogenicity.
Insufficient data to recommend use
Maraviroc
(MVC)
No PK studies in pregnancy. No evidence of
teratogenicity in rats or rabbits..
Insufficient data to recommend use
65
August 2015
Integrase Inhibitors
Comments on Use during Pregnancy
Dolutegravir
(DTG)
No PK data in pregnancy; insufficient data to make dosing
recommendation. Unknown placental transfer.
Insufficient data to assess for teratogenicity in humans; no
evidence of teratogenicity in mice, rats or rabbits.
Elvitegravir
(EVG)
No PK data in pregnancy; insufficient data to make dosing
recommendation. No data on placental transfer.
Insufficient data to assess for teratogenicity in humans; no
evidence of teratogenicity in rats or rabbits
Raltegravir
(RAL)
66
Decreased levels 3rd trimester but no dosing change
needed. High placental transfer. Insufficient data to assess
teratogenicity in humans. Increased skeletal variants in rats,
no increase in defects in rabbits. Case report of severe
increase in transaminases. Chewable tablets contain
phenylalanine.
August 2015
Pharmacokinetic Enhancers
Comments on Use during Pregnancy
Cobicistat
(COBI)
No PK data in pregnancy. No data on placental transfer.
Insufficient data to assess for teratogenicity in humans. No
evidence of teratogenicity in rats or rabbits.
Ritonavir
(RTV)
Recommended only as low dose PK booster for other PIs. No
dosage adjustment needed when used as booster.
Minimal to low placental transfer. No evidence of human
teratogenicity.
Oral solution not optimal during pregnancy owing to alcohol
content.
67
August 2015
HIV-Infected Pregnant Women Who Are
Currently Receiving Antiretroviral Therapy (1)
 In general, HIV-infected pregnant women receiving cART who
present for care in the 1st trimester should continue treatment
during pregnancy, assuming the regimen is tolerated and
effective in suppressing viral replication (HIV-1 viral load less
than lower limits of detection of the assay) (AII).
 It is recommended that efavirenz be continued in pregnant
women receiving efavirenz-based cART who present for
antenatal care in the first trimester provided the regimen is
achieving virologic suppression (CIII).
68
August 2015
HIV-Infected Pregnant Women Who Are
Currently Receiving Antiretroviral Therapy (2)
 Rationale for continuing EFV in pregnancy:
 1st-trimester exposure is not definitely
associated with increased risk of neural tube
defects.
 The risk of neural tube defects is limited to the
first 5-6 weeks of pregnancy, before most
pregnancies are recognized.
 Unnecessary ARV changes during pregnancy
may increase the risk of loss of virologic control
and transmission to infant.
69
August 2015
HIV-Infected Pregnant Women Who Are
Currently Receiving Antiretroviral Therapy (3)
 HIV antiretroviral drug-resistance testing should be
performed to assist in the selection of active drugs when
changing antiretroviral regimens in pregnant women on
therapy with virologic failure and HIV RNA levels >1,000
copies/mL (AI). In individuals with HIV RNA levels >500
but <1,000 copies/mL, testing may be unsuccessful but
should still be considered (BII).
* See Lack of Viral Suppression
70
August 2015
Pregnant Women Who Are ARV-Experienced
but Not Currently on ARVs (1)
 Obtain an accurate history of all prior ARV regimens used for
treatment of HIV disease or prevention of transmission, including
virologic efficacy, tolerance, results of prior resistance testing, and
any adherence issues (AIII).
 If HIV RNA is above the threshold for resistance testing (i.e., >500
to 1,000 copies/mL), do ARV drug-resistance studies before
starting ART (see Antiretroviral Drug Resistance and Resistance
Testing in Pregnancy) (AIII).
 Consideration should be given to initiating cART prior to receiving
results of antiretroviral drug resistance studies in light of data
demonstrating an association between earlier viral suppression
and lower risk of HIV transmission. The antiretroviral regimen
should be modified based on the results of the resistance assay, if
necessary (BIII).
71
August 2015
Pregnant Women Who Are ARV-Experienced
but Not Currently on ARVs (2)
 Choose and initiate a cART regimen based on results of
resistance testing and prior history of cART while avoiding
drugs with teratogenic potential or with known adverse
potential for the mother or fetus/infant (AII).
 Consider obtaining a consultation with specialists in
treatment of HIV infection about the choice of a cART
regimen for women who previously received ARV (AIII).
 Perform repeat ARV resistance testing (AI), assess
adherence, and consult with an HIV treatment specialist to
guide changes in ARV drugs in women who do not achieve
virologic suppression on their ARV regimens.
72
August 2015
Pregnant Women Who Are ARV-Experienced but
Not Currently on ARVs (3)
 Pregnant women with HIV infection who have
received ARVs previously for prevention of
perinatal transmission:
 Concern that time-limited use may lead to genotypic
resistance and reduced efficacy in subsequent
pregnancies.
 Rates of resistance appear to be low after prophylaxis
with cART.
 NVP prophylaxis may cause resistance and failure of
subsequent NVP-based cART.
 Longer, more complex ARV tails after stopping pregnancylimited NVP appear to reduce risk of resistance.
73
August 2015
Pregnant Women Who Are ARVExperienced but Not Currently on ARVs (4)
 Treatment failure has not been demonstrated
with reinitiation of cART following prophylactic
use of cART in pregnancy.
 Pregnant women with HIV infection who have
received ARVs previously for their own health:
 Choice of ARV regimen may be challenging and will
vary by:





74
History of ART and adherence problems
Indication for stopping treatment
Efficacy of previous ART
Results of past and current resistance testing
Lab testing, including HLA-B*5701 prior to abacavir use
August 2015
Maternal and Fetal Monitoring during
Pregnancy (1)
 More frequent HIV RNA (viral load)
monitoring in pregnancy is recommended
because of the importance of rapid and
persistent viral suppression in preventing
perinatal HIV transmission.
 Viral suppression generally achieved in 12-24
weeks in ARV-naive adherent individuals. May
take longer in some patients and may be
dependent on starting viral load.
75
August 2015
Maternal and Fetal Monitoring during
Pregnancy (2)
 Monitor HIV RNA:
 At the initial visit (AI)
 2-4 weeks after initiating or changing ARV drug
regimens (BI)
 Monthly until HIV RNA is undetectable (BIII)
 At least every 3 months during pregnancy (BIII)
 HIV RNA should also be assessed at
approximately 34-36 weeks’ gestation to
inform decisions about mode of delivery and
about infant ARV prophylaxis (AIII).
76
August 2015
Maternal and Fetal Monitoring during
Pregnancy (3)
 Monitor CD4 count:
 At initial antenatal visit (AI).
 At least every 3 months during pregnancy (BIII).
 Can monitor CD4 count every 6 months in
patients on cART with consistently suppressed
viral load who have CD4 counts well above the
threshold for opportunistic infection risk (CIII).
77
August 2015
Maternal and Fetal Monitoring during
Pregnancy (4)
 Genotypic resistance testing should be performed
at baseline in all HIV-infected pregnant women
with HIV RNA levels >1,000 copies/mL (A1).
 In individuals with HIV RNA levels >500 but <1,000
copies/mL, testing may be unsuccessful but should
still be considered (BII).
 Tests should be performed whether the women are
antiretroviral-naive or currently on therapy (AIII).
78
August 2015
Maternal and Fetal Monitoring during
Pregnancy (4)
 HIV drug-resistance studies should be performed
before modifying antiretroviral regimens for those
entering pregnancy with detectable HIV RNA levels
that are above the threshold for resistance testing
(i.e., >500 to 1,000 copies/mL) while receiving
antiretroviral drugs.
 They should also be performed on women who
have suboptimal viral suppression after starting
ARV drugs during pregnancy (AII).
79
August 2015
Maternal and Fetal Monitoring during
Pregnancy (5)
 Monitoring for complications of ARV drugs should be based on what is
known about the adverse effects of the drugs a woman is receiving (AIII).
 Women taking cART during pregnancy should undergo standard glucose
screening at 24-28 weeks’ gestation (AIII).
 Some experts would perform earlier glucose screening in women
receiving PI-based regimens initiated before pregnancy, similar to
recommendations for women with high risk factors for glucose intolerance
(BIII).
 Early ultrasound is recommended to confirm gestational age and, if
scheduled cesarean delivery is necessary, to guide its timing (AII).
80
August 2015
Maternal and Fetal Monitoring during
Pregnancy (6)
 In women on effective cART, no perinatal transmissions
have been reported after amniocentesis, but a small risk
of transmission cannot be ruled out.
 If amniocentesis is indicated, it should be performed only
after initiation of an effective cART regimen and, ideally,
when HIV RNA levels are undetectable (BIII).
 In women with detectable HIV RNA levels in whom
amniocentesis is deemed necessary, consultation with an
expert should be considered (BIII).
 Consider using cell-free, fetal DNA as a noninvasive
alternative to decrease need for amniocentesis.
81
August 2015
ARV Resistance during Pregnancy (1)
 Drug resistance:
 Is one of the major factors leading to treatment failure.
 May limit future maternal treatment options and
decrease effectiveness of ARV prophylaxis during
current and future pregnancies.
 Increased risk of resistance during pregnancy with:
 Nausea and vomiting (poor ARV adherence or
absorption).
 PK changes.
 Postpartum:
 If taking ARVs with low genetic barrier to resistance
and simultaneous discontinuation of drugs with
different half-lives.
82
August 2015
ARV Resistance during Pregnancy (2)
 HIV drug-resistance studies should be performed before starting ARV
regimens in all ARV-naïve pregnant women whose HIV RNA levels (>
500 to 1,000 copies/mL) are above the threshold for resistance testing
unless they have already been tested for ARV resistance (AIII).
 HIV drug-resistance studies should be performed before modifying ARV
regimens for those entering pregnancy with a detectable HIV RNA levels
that are above the threshold for resistance testing while receiving ARV
drugs and those who have suboptimal viral suppression after starting
ARV drugs during pregnancy (AII).
 cART should be initiated in pregnant women prior to receiving results of
ARV-resistance studies. The ARV regimen should be modified, if
necessary, based on the results of the resistance assay (BIII).
83
August 2015
ARV Resistance during Pregnancy (3)
 Documented ZDV resistance does not affect the indications for use of
intrapartum ZDV (BIII).
 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 (AIII).
 HIV-infected pregnant women should be given cART to maximally
suppress viral replication, which is the most effective strategy for
preventing development of resistance and minimizing risk of perinatal
transmission (AII).
84
August 2015
ARV Resistance during Pregnancy (4)
 All pregnant and postpartum women should be
counseled about the importance of adherence to
prescribed ARV medications to reduce the potential
for development of resistance (AII).
 Several studies demonstrated that women’s adherence to
cART may worsen in the postpartum period.
 Clinicians should specifically address adherence including
evaluating specific factors that facilitate or impede
adherence.
85
August 2015
ARV Resistance during Pregnancy (5)
 To minimize development of resistance, pregnant women
who receive an NNRTI-based combination ARV regimen
that is discontinued after delivery should receive either
dual NRTI agents alone (AI) or with a PI (BII) for 7-30 days
(AII) after stopping the NNRTI drug.
 NNRTIs have longer half-lives than other ARVs.
 The optimal interval between stopping an NNRTI and the
other ARV drugs is unknown.
86
August 2015
Lack of Viral Suppression (1)
 Because maternal antenatal viral load correlates
with risk of perinatal transmission of HIV,
suppression of HIV RNA to undetectable levels
should be achieved as rapidly as possible (AII).
 High baseline viral load and later start of ART
reduce the likelihood of HIV RNA suppression at
delivery.
87
August 2015
Lack of Viral Suppression (2)
 If an ultrasensitive HIV RNA assay indicates failure of
viral suppression (persistent HIV RNA >20-75 copies/mL,
depending on the assay used) after an adequate period
of treatment:
 Assess adherence and resistance (if HIV RNA high enough
for resistance testing) (AII).
 Consult an HIV treatment expert and consider possible
cART modification (AIII).
 Scheduled C-section is recommended for HIV-infected
pregnant women who have HIV RNA >1,000 copies/mL
near the time of delivery (AII).
88
August 2015
Lack of Viral Suppression (3)
 Addition of RAL in late pregnancy if the HIV RNA
is high or if incomplete virologic suppression:
 RAL can rapidly suppress HIV RNA.
 Efficacy and safety of this approach have not been
evaluated and it is not routinely recommended.
 In setting of drug resistance, addition of RAL may lead
to RAL resistance.
89
August 2015
Stopping ARVs during Pregnancy (1)
 HIV-infected women on cART who present for care during
the 1st trimester should continue treatment during pregnancy
(AII).
 ART should not be interrupted in women taking EFV who present in
the 1st trimester, if the HIV RNA is suppressed.
 If an ARV drug regimen is stopped acutely for severe or lifethreatening toxicity, severe pregnancy-induced hyperemesis
unresponsive to antiemetics, or other acute illnesses that
preclude oral intake, all ARV drugs should be stopped
simultaneously and ARV therapy should be reinitiated as
soon as possible (AIII).
 Restart all ARV drugs simultaneously with same or new
regimen depending on situation/toxicity.
90
August 2015
Stopping ARVs during Pregnancy (2)
 EFV can be detected in the blood for longer than 3
weeks after discontinuation. Consider assessing
rebound viremia and potential drug resistance if
stopped if EFV containing regimen is stopped for
more than a few days.
 If a NVP containing regimen has been stopped for
more than 7 days, a 2 week dose escalation is
recommended when restarting NVP.
91
August 2015
HIV/Hepatitis B Virus Coinfection (1)
 All HIV-infected pregnant women should be screened during
pregnancy for hepatitis B virus (HBV) and hepatitis C virus (HCV)
unless they are known to be coinfected or have already been
screened during the current pregnancy (AIII).
 All HIV-infected pregnant women who screen negative for HBV
(surface antigen, core antibody and surface antibody) should receive
the HBV vaccine series (AII).
 Women with chronic HBV who have not already received the hepatitis
A virus (HAV) vaccine series should be screened for immunity to HAV
because they are at increased risk of complications from coinfection
with other viral hepatitis infections (AIII).
 HAV vaccine series if negative for HAV IgG.
92
August 2015
HIV/Hepatitis B Virus Coinfection (2)
 The management of HIV/HBV coinfection in pregnancy is
complex; consultation with an expert in HIV and HBV is
strongly recommended (AIII).
 Interferon-alfa and pegylated interferon-alfa are not
recommended during pregnancy (AIII).
 All pregnant women with HIV/HBV coinfection should
receive cART. Antepartum cART should include TDF plus
3TC or FTC (AI).
 These drugs are active against HIV and HBV.
 Initiation of an ARV regimen that does not include anti-HBV drugs
may be associated with reactivation of HBV and development of
IRIS.
93
August 2015
HIV/Hepatitis B Virus Coinfection (3)
 Pregnant women with HIV/HBV coinfection receiving
ARVs should be counseled about signs and symptoms of
liver toxicity, and liver transaminases should be assessed
1 month following initiation of ARV drugs and at least
every 3 months thereafter during pregnancy (BIII).
 If ARVs are discontinued postpartum in women with
HIV/HBV coinfection, frequent monitoring of liver function
tests for potential exacerbation of HBV infection is
recommended, with prompt reinitiation of treatment for
both HIV and HBV if a flare is suspected (BIII).
94
August 2015
HIV/Hepatitis B Virus Coinfection (4)
 Decisions concerning mode of delivery in HIV/HBVcoinfected pregnant women should be based on
standard obstetric and HIV-related indications alone.
HBV coinfection does not necessitate cesarean delivery,
if not otherwise indicated (BIII).
 Within 12 hours of birth, infants born to women with HBV
infection should receive hepatitis B immune globulin and
should initiate the HBV vaccine series (A1).
 Timing of later doses in series differs between infants > 2,000 g
and < 2,000 g. The regimen is 95% effective in preventing HBV.
 Post-vaccination testing for anti-HBs and HBsAg should be
performed after completion of the vaccine series, at age 9
months to 18 months.
95
August 2015
HIV/Hepatitis C Virus Coinfection (1)
 All HIV-infected pregnant women should be screened during the
current pregnancy for HBV and HCV unless they are known to
be coinfected (AIII).
 Use the most sensitive immunoassays to detect HCV antibody
(anti-HCV) (AIII).
 All HIV-infected pregnant women who screen negative for HBV
should receive the HBV vaccination series (AII).
 Women with chronic HCV infection should also be screened for
hepatitis A virus (HAV) because they are at increased risk of
complications from coinfection with other viral hepatitis
infections (AIII).
96
August 2015
HIV/Hepatitis C Virus Coinfection (2)
 The management of HIV/HCV coinfection in pregnancy is
complex because currently approved medications for HCVare
not recommended during pregnancy, and no safety data
exist for use of the recently approved HCV oral
medications in pregnant women (AIII).
 If considering treatment of HCV in a coinfected pregnant woman,
consultation with an expert in HIV and HCV is strongly
recommended (AIII).
 Interferon-alfa and pegylated interferon-alfa are not
recommended and ribavirin is contraindicated during pregnancy
(AII).
 No pregnancy data on newer oral agents.
97
August 2015
HIV/Hepatitis C Virus Coinfection (3)
 Recommendations for ARV drug use during pregnancy are the same
for HIV-infected women whether or not they have chronic HCV (BIII).
 Pregnant women with HIV/HCV coinfection receiving ARV drugs
should be counseled about signs and symptoms of liver toxicity, and
liver transaminases should be assessed 1 month following initiation
of ARV drugs and at least every 3 months thereafter during
pregnancy (BIII).
 Decisions concerning mode of delivery in HIV/HCV-coinfected
pregnant women should be based on standard obstetric and HIVrelated indications alone; HCV coinfection does not necessitate
cesarean delivery, if not otherwise indicated (AIII).
98
August 2015
HIV/Hepatitis C Virus Coinfection (4)
 Infants born to women with HIV/HCV coinfection should
be evaluated for HCV infection with anti-HCV antibody
testing after age 18 months (AII).
 Infants who screen positive should undergo confirmatory HCV
RNA testing. HCV RNA virologic testing can be done after age 2
months, if earlier diagnosis is indicated (AIII).
 Because HCV viremia can be intermittent, 2 negative HCV RNA
test results at or after age 2 months, including 1 test at or after
age 12 months, are needed to definitively exclude HCV infection
(BIII).
 Children are considered to be HCV infected if they have 2 or
more positive HCV RNA result results at any age or are HCV
antibody positive beyond age 18 months (AII).
99
August 2015
HIV-2 Infection and Pregnancy (1)
 HIV-2 is endemic in West African countries and
in parts of India. It also occurs in France and
Portugal with large numbers of immigrants from
these regions. It remains rare in the United
States.
 In the United States, 166 cases met CDC criteria
for HIV-2 diagnosis between 1998 and 2010.
100
August 2015
HIV-2 Infection and Pregnancy (2)
 HIV-2 infection should be considered in pregnant women
who are from ̶ or have partners from ̶ countries in which
the disease is endemic, who have positive results on an
HIV-1/HIV-2 antibody or HIV-1/HIV-2 antigen/antibody
immunoassay. They should be tested with a supplemental
HIV-1/HIV-2 antibody differentiation assay. If they are
indeed HIV-2 infected it would show negative HIV-1
antibodies and positive HIV-2 antibodies (AII).
101
August 2015
HIV-2 Infection and Pregnancy (3)
 2014 CDC new HIV testing algorithm may
enhance the diagnosis of HIV-2.
 1st test with HIV-1/HIV-2 antigen antibody combination
assay (Abbott Architect HIV Ag/Ab combo assay,
BioRad GS Combo Ag/Ab EIA, Alere Determine).
 If positive, use a FDA approved 2nd generation
antibody assay Multispot HIV-1/HIV-2 Rapid Test (BioRad Laboratories) and GeeniuS (Bio-Rad
Laboratories).
102
August 2015
HIV-2 Infection and Pregnancy (4)
 Viral load assays for HIV-2 are not commercially available.
 University of Washington and NY State Department of
Health offer HIV-2 viral load assays. See Guidelines.
 No validated HIV-2 genotype or phenotype resistance
assays are available in the United States but internet tool
by European experts available (http://www.hiv-grade.de).
 All HIV-2 cases should be reported to the state or local
health department; they can arrange confirmative HIV-2
testing by CDC.
103
August 2015
HIV-2 Infection and Pregnancy (5)
 A regimen with 2 NRTIs and a boosted PI is
recommended for HIV-2-infected pregnant
women who require treatment for their own
health because they have significant clinical
disease or CD4 count of <500 cells/µL (AIII).
 Preferred ART regimen for HIV-2-infected
pregnant women who require treatment:
 Lopinavir/ritonavir + ZDV/3TC or ABC/3TC or
TDF/FTC (AIII).
104
August 2015
HIV-2 Infection and Pregnancy (6)
 Optimal prophylactic regimens have not been
defined for HIV-2-infected pregnant women who do
not require treatment for their own health (i.e., CD4
counts >500 cells/µL and no significant clinical
disease). Experts have recommended:
 2 NRTIs plus lopinavir/ritonavir for prophylaxis, with the
drugs stopped postpartum (BIII); or
 Zidovudine prophylaxis alone during pregnancy and
intrapartum (BIII).
105
August 2015
HIV-2 Infection and Pregnancy (7)
 NNRTIs and enfuvirtide are not active against HIV-2 and
should not be used for treatment or prophylaxis (AIII).
 All infants born to HIV-2-infected mothers should receive
the standard 6-week zidovudine prophylactic regimen
(BIII).
 In the United States, where safe infant formula is readily
available, breast-feeding is not recommended for infants of
HIV-2-infected mothers (AIII).
106
August 2015
Pregnancy in Women with
Perinatal HIV Infection (1)
 Increasing number of individuals with perinatally acquired
HIV now reaching childbearing age and becoming pregnant
or fathering children.
 The components of prenatal care and general principles of
cART and HIV management do not differ between pregnant
women who were perinatally infected and those who
acquired HIV infection in other ways.
 There are unique challenges related to adherence and risk
of ARV resistance due to extensive cART exposure.
 Consultation with experts in HIV and pregnancy
recommended.
107
August 2015
Pregnancy in Women with
Perinatal HIV Infection (2)
 Some studies suggest women with perinatal may have
elevated rates of preterm and small-for gestational-age
infants compared to women with horizontal HIV infection,
but this was not seen in all studies. Data are limited.
 When appropriate ART and prenatal management occurs
and optimal viral load suppression is attained, the risk of
perinatal transmission does not appear to be increased.
 Pregnancy may create additional burdens in the transition
from pediatric/adolescent to adult care.
 Developmentally appropriate adherence counseling and counseling
for reproductive health and pregnancy prevention are important.
108
August 2015
Acute HIV Infection (1)
 When acute retroviral syndrome is suspected in pregnancy
or during breast-feeding, a plasma HIV RNA test should be
obtained in conjunction with a routine HIV antibody test or
an antigen/antibody immunoassay test (AII).
 Repeat HIV antibody testing during the 3rd trimester is
recommended for pregnant women with initial negative HIV
antibody test results who are (AII):
 known to be at risk of acquiring HIV.
 receiving care in facilities that have an HIV incidence among
pregnant women of at least 1 per 1,000 per year.
 are incarcerated.
 reside in jurisdictions with elevated HIV incidence.
109
August 2015
Acute HIV Infection (2)
 All pregnant women with acute or recent HIV infection should start
a combination ARV regimen as soon as possible to prevent
perinatal transmission, with the goal of suppressing plasma viral
load to below detectable levels (AI).
 In women with acute HIV infection, baseline genotypic resistance
testing should be performed simultaneously with initiation of the
combination ARV regimen, and the ARV regimen should be
adjusted, if necessary, to optimize virologic response (AIII).
 Because clinically significant resistance to PIs is less common
than resistance to NNRTIs in ARV-naive individuals, an RTVboosted PI-based regimen should be initiated (AIII).
110
August 2015
Acute HIV Infection (3)
 Primary or acute HIV infection during pregnancy or
breast-feeding is associated with increased risk of
transmission.
 Counsel all pregnant or breast-feeding women about
prevention of HIV. Reinforce importance of using
condoms.
 Consider the use of pre- or postexposure ARV
prophylaxis for those whose partners are HIV infected.
 Maintain a high level of suspicion for acute HIV in women
who have a compatible clinical syndrome, even if highrisk behaviors are not reported.
111
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AIDS Education and Training Center
National Coordinating Resource Center
INTRAPARTUM CARE
Intrapartum ARV Therapy/Prophylaxis (1)
 Women should continue their antepartum combination
ARV drug regimen on schedule as much as possible
during labor and before scheduled cesarean delivery (AIII).
 Intravenous (IV) ZDV should be administered to HIVinfected women with VL >1,000 copies/mL (or unknown
VL) near delivery (AI), but is not required for HIV-infected
women receiving cART regimens who have VL ≤1,000
copies/ mL consistently during late pregnancy and near
delivery and no concerns regarding adherence to the
regimen (BII).
113
August 2015
Intrapartum ARV Therapy/Prophylaxis (2)
 Scheduled cesarean delivery at 38 weeks’ gestation
(compared to 39 weeks for most indications) is
recommended for women who have HIV RNA >1,000
copies/mL near delivery (AI).
 Women who present in labor with unknown HIV status
should undergo expedited HIV testing (AII). If positive result:
 Do a confirmatory HIV test ASAP and initiate maternal (IV ZDV) and
infant (combination ARV prophylaxis) ARV drugs pending results of
the confirmatory test (AII).
 If the maternal confirmatory HIV test result is positive, infant ARV
drugs should be managed as discussed under Infant ARV
Prophylaxis (AI); if the maternal confirmatory result is negative,
maternal and infant ARV drugs should be stopped.
114
August 2015
Intrapartum ARV Therapy/Prophylaxis (3)
 The additional benefit of IV ZDV in women on
cART regimens has not been evaluated in
randomized studies.
 In nonrandomized studies of women on cART,
addition of intrapartum ZDV appears to reduce
risk of perinatal transmission if HIV RNA is not
consistently suppressed to <1,000 copies/mL
near time of delivery.
115
August 2015
Transmission and Mode of Delivery (1)
 Scheduled cesarean delivery at 38 weeks’
gestation to minimize perinatal transmission of
HIV is recommended for women with HIV RNA
levels >1000 copies/mL or unknown HIV levels
near the time of delivery, irrespective of
administration of antepartum antiretroviral drugs
(AII).
116
August 2015
Transmission and Mode of Delivery (2)
 For pregnant women receiving cART with HIV
RNA levels <1,000 copies/mL :
 Scheduled cesarean delivery is not routinely
recommended due to the low rate of perinatal
transmission in this group and the potential for
increased complications following cesarean
delivery in HIV-infected women (AII).
 C-sections performed for standard obstetrical
indications should be scheduled for 39 weeks’
gestation (AII).
117
August 2015
Transmission and Mode of Delivery (3)
 Because there is insufficient evidence to
determine whether cesarean delivery after rupture
of membranes or onset of labor reduces the risk
of perinatal HIV transmission, management of
women originally scheduled for cesarean delivery
who present with ruptured membranes or in labor
must be individualized at the time of presentation
(BII).
 Consultation with an expert in perinatal HIV (e.g.,
telephone consultation with the National HIV/AIDS
Clinician Consultation Center at (888)448-8765) may be
helpful in rapidly developing an individualized plan.
118
August 2015
Transmission and Mode of Delivery (4)
 Women with HIV infection should be counseled
that HIV infection may put them at higher risk of
surgical complications of cesarean delivery (AII).
 If unscheduled cesarean delivery is performed
and IV ZDV administration is indicated (HIV RNA
> 1,000 copies/mL), consider shortening the
interval between initiation of IV ZDV and
delivery.
 Some experts recommend proceeding with
delivery after giving the loading dose of IV ZDV.
119
August 2015
Other Intrapartum Management Considerations (1)
 The following should generally be avoided
because of a potential increased risk of
transmission, unless there are clear obstetric
indications:
 Artificial rupture of membranes (BIII).
 Routine use of fetal scalp electrodes (BIII).
 Operative delivery with forceps or vacuum
extractor and/or episiotomy (BIII).
120
August 2015
Other Intrapartum Management Considerations (2)
 Consider the ARVs a woman is receiving when treating
excessive postpartum bleeding resulting from uterine
atony:
 If receiving a cytochrome (CYP) 3A4 enzyme inhibitor (e.g.,
a PI), use methergine only if no alternative treatments are
available and the need for pharmacologic treatment
outweighs the risks. If methergine is used, it should be
administered in the lowest effective dose for the shortest
possible duration (BIII).
 If receiving a CYP3A4 enzyme inducer such as NVP, EFV,
or etravirine, additional uterotonic agents may be needed
because of the potential for decreased methergine levels
and inadequate treatment effect (BIII).
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AIDS Education and Training Center
National Coordinating Resource Center
POSTPARTUM CARE
Postpartum Care (1)
 Decisions about continuing cART should be
made in consultation with the woman and her
HIV provider, ideally before delivery. cART is
recommended for all HIV-infected individuals to
reduce the risk of disease progression and to
prevent sexual HIV transmission (AIII).
 Take into account current recommendations for the
initiation of cART in adults, HIV RNA levels, adherence
issues, whether a woman has an HIV-uninfected sex
partner, and patient preferences.
123
August 2015
Postpartum Care (2)
 Because the immediate postpartum period poses
unique challenges to antiretroviral adherence,
arrangements for new or continued supportive
services should be made before hospital discharge
for women continuing cART (AII).
 Counsel women about the challenge of
adherence in the postpartum period.
 Remain vigilant for signs of depression, intimate
partner violence, and drug or alcohol use.
 Consider simplifying cART regimens to improve
adherence.
124
August 2015
Postpartum Care (3)
 Contraceptive counseling should be a critical
aspect of postpartum care (AIII).
 Ideally contraception will also have been addressed in the
prenatal period.
 Lack of breastfeeding is associated with earlier return of
fertility. Women may be at risk of pregnancy shortly after
delivery. Ovulation occurs as early as 6 weeks postpartum,
even before return of menses.
 Encourage dual-protection strategy of condom use plus a
second highly effective contraceptive
 Review possible drug interactions of specific ARV drugs with
hormonal contraceptives before prescribing
 Encourage safer sex practices and secondary transmission
prevention.
125
August 2015
Postpartum Care (4)
 Women with a positive rapid HIV antibody test
result during labor require immediate linkage to
HIV care and comprehensive follow-up including
confirmation of HIV infection. If infection
confirmed, the following are indicated (AII):




126
Full health assessment,
Evaluation for associated medical conditions,
Counseling related to HIV diagnosis,
Assessment of need for cART and
opportunistic infection prophylaxis.
August 2015
Postpartum Care (5)
 Breast-feeding is not recommended for HIVinfected women in the United States (AII).
 cART dramatically reduces but does not eliminate
breast milk transmission.
 Safer infant feeding options are available.
 Other potential risks include toxicity to the neonate or
ARV resistance should transmission occur due to
variable passage of ARV drugs into breast milk.
 Health care providers should routinely inquire
about premastication, instruct HIV-infected
caregivers against this feeding practice, and
advise on safer feeding options.
127
August 2015
AIDS Education and Training Center
National Coordinating Resource Center
CARE OF THE NEONATE
Infant Antiretroviral Prophylaxis (1)
 A 6 week neonatal ZDV prophylaxis regimen is
generally recommended for all HIV-exposed
neonates to reduce perinatal transmission of HIV
(AI). However, a 4-week neonatal zidovudine
prophylaxis regimen can be considered for full-term
infants when:
 The mother has received standard cART during
pregnancy with consistent viral suppression, and
 There are no concerns related to maternal adherence
(BII).
129
August 2015
Infant Antiretroviral Prophylaxis (2)
 ZDV, at gestational age-appropriate doses, should be
initiated as close to the time of birth as possible, preferably
within 6 to 12 hours of delivery (AII).
 Infants at higher risk of HIV acquisition should receive
prophylaxis with ZDV and NVP. This includes infants born
to women who:
 received only intrapartum ARV drugs (AI), or
 have not received antepartum or intrapartum antiretroviral
drugs (AI), or
 have received antepartum ARV drugs but have had
suboptimal viral suppression (>1000 copies/mL) near delivery
(BIII).
130
August 2015
Infant Antiretroviral Prophylaxis (3)
 The prophylaxis regimen for infants at higher risk
of HIV acquisition:
 ZDV for 6 weeks combined with
 3 doses of NVP in the first week of life
 1st dose at birth
 2nd dose 48 hours later
 3rd dose 96 hours after the second dose.
 Begin regimen as soon as possible after birth.
131
August 2015
Infant Antiretroviral Prophylaxis (4)
 Some experts recommend triple-ARV prophylaxis
for infants at higher risk of HIV acquisition
although there are no data demonstrating
improved efficacy for a three-drug regimen over a
two-drug regimen in prevention of transmission.
 A decision to administer triple-ARV prophylaxis should
be made only in consultation with a pediatric HIV
specialist, preferably before delivery, and should be
accompanied by parental counseling on the potential
risks (e.g., neonatal toxicity), and benefits (e.g.,
prevention of perinatal transmission) of this approach
(BIII).
132
August 2015
Infant Antiretroviral Prophylaxis (5)
 In the United States, the use of antiretroviral drugs
other than zidovudine and nevirapine cannot be
recommended in premature infants as prophylaxis
to prevent transmission because of lack of dosing
and safety data (BIII).
 For additional information refer to the Pediatric
Antiretroviral Guidelines, Specific Issues in Antiretroviral
Therapy in Neonates.
 The Clinician Consultation Center (1-888-4488765) provides free clinical consultation on all
aspects of perinatal HIV, including infant care.
133
August 2015
Infant Antiretroviral Prophylaxis (6)
 For infants born to mothers with unknown HIV
status:
 Conduct expedited HIV testing of mothers and/or
infants as soon as possible, either during labor or
after birth, with immediate initiation of infant
antiretroviral prophylaxis if the initial expedited
test is positive (AII).
 If supplemental testing is negative, antiretroviral
prophylaxis can be discontinued.
See Diagnosing HIV Infection in Infants
134
August 2015
Infant Antiretroviral Prophylaxis (7)
 Infants born to mothers with known or suspected
ARV-resistant virus:
 Optimal ARV prophylaxis regimen for
newborns is unknown.
 Consult with a pediatric HIV specialist or with
the Clinician Consultation Center before
delivery.
 Even with maternal ZDV resistance, a 6-week
course of infant ZDV is recommended.
 Thee is no evidence that prophylactic regimens
customized based on maternal drug resistance
are more effective than standard regimens.
135
August 2015
Short-Term ARV Safety in Neonatal
Prophylaxis (1)
 ZDV: transient hematologic toxicity (mainly anemia).
 3TC: in combination with ZDV may cause more severe
anemia and neutropenia.
 TDF and FTC: limited data on dosing and safety not well
defined; not recommended for infant prophylaxis.
 NVP: no cases of severe rash or hepatotoxicity with
neonatal prophylaxis.
 Resistance may occur in infants who become infected despite
prophylaxis.
136
August 2015
Short-Term ARV Safety in Neonatal
Prophylaxis (2)
 PIs: not recommended for infant prophylaxis during the
first few weeks of life due to lack of dosing and safety
data – see also Pediatric ARV guidelines.
 In addition, LPV/r solution contains 42.4% alcohol and 15.3% propylene
glycol. It should not be administered 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.
 RAL: Only integrase inhibitor with a pediatric formulation
but not FDA-approved for use in infants aged <4 weeks
or weight <3 kg. Not recommended until adequate PK
and safety data are available.
137
August 2015
Initial Postnatal Management of the HIVExposed Neonate (1)
 Obtain a CBC with differential as a baseline
evaluation before initiation of ARV prophylaxis
(BIII).
 Decisions about the timing of subsequent
hematologic monitoring is based on (CIII):






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Baseline values,
Gestational age and clinical condition of infant,
ZDV dosage administered,
Receipt of other ARV drugs,
Concomitant medications,
Maternal ARV regimen.
August 2015
Initial Postnatal Management of the HIVExposed Neonate (2)
 Consider more frequent monitoring for infants
exposed to combination ARV regimes in utero
or neonatally:




139
CBC,
Serum chemistry,
Liver function,
Bilirubin levels (ATV exposure).
August 2015
Initial Postnatal Management of the HIVExposed Neonate (3)
 For infants receiving combination
ZDV/3TC-containing ARV prophylaxis
regimens:
 Hemoglobin and neutrophil counts
should be remeasured 4 weeks after
initiation of prophylaxis (A1).
140
August 2015
Initial Postnatal Management of the HIVExposed Neonate (4)
 If hematologic abnormalities are identified, decisions on
whether to continue infant ARV prophylaxis need to be
individualized. Consultation with an expert in pediatric
HIV infection is advised if early discontinuation of
prophylaxis is considered (CIII). Considerations about
whether to continue ARV prophylaxis include:




Extent of abnormality,
Related symptoms,
Duration of infant ARV prophylaxis,
Risk of HIV infection.
 May consider reducing ARV prophylaxis to 4 weeks
when mother has received cART with consistent viral
suppression and there are no adherence concerns.
141
August 2015
Initial Postnatal Management of the HIVExposed Neonate (5)
 Routine measurement of serum lactate is not
recommended unless infant develops severe
clinical symptoms of unknown etiology. (CIII)
 Particularly neurologic symptoms.
 In symptomatic infants with significantly
abnormal serum lactate levels (>5 mmol/L):
 Discontinue ARV prophylaxis.
 Consult a pediatric HIV specialist for alternative
prophylaxis.
142
August 2015
Diagnosing HIV Infection in Infants (1)
 Diagnostic HIV tests for infants:
 Use HIV nucleic acid amplification virologic
assays (e.g., HIV DNA and RNA PCR) (AII).
 Maternal HIV antibodies cross placenta and
are detectable in HIV-exposed infants for up
to 18 months.
 Standard antibody tests cannot be used to
diagnose HIV infection in infants.
143
August 2015
Diagnosing HIV Infection in Infants (2)
 Virologic tests should be performed at (AII):
 14-21 days,
 1-2 months, and
 4-6 months.
 Virologic test may be performed at birth:
 If mother did not have good virologic control during
pregnancy, or
 If adequate follow-up cannot be assured.
 Confirm a positive HIV virologic test with a
second virologic test on a different specimen.
144
August 2015
Diagnosing HIV Infection in Infants (3)
 HIV infection in an infant is diagnosed by 2
positive virologic tests on separate
specimens.
 Some experts prefer to use HIV DNA assays
(rather than HIV RNA) for infant HIV
diagnosis, although the effects of maternal or
infant ARV exposure on the sensitivity of
virologic testing—particularly HIV RNA
assays—are unknown.
145
August 2015
Diagnosing HIV Infection in Infants (4)
 HIV infection is excluded:
 Presumptively by 2 negative virologic tests, 1 at age
≥14 days and 1 at age ≥1 month.
 Definitively (in non-breast-fed infants) by 2 negative
virologic tests, 1 at age ≥1 month or older and 1 at age
≥4 months.
 Many experts confirm negative status by
antibody testing at 12-18 months (HIV
antibodies can sometimes occur at or beyond
18 months).
 Diagnosis of non-subtype-B HIV may be difficult:
see Pediatric ARV Guidelines.
146
August 2015
Postnatal Management of the HIV-Exposed
Neonate: Prophylaxis and Immunizations
 To prevent Pneumocystis jirovecii pneumonia
(PCP), prophylaxis should begin at age 4-6
weeks, after completion of ARV prophylaxis (AII).
 Unless HIV infection can be presumptively excluded
 Evaluate and treat infants as indicated for
transmittable maternal coinfections identified
through history or physical evaluation.
 HIV-exposed infants should follow the routine
immunization schedule.
147
August 2015
Infant Feeding Practices and Risk of HIV
Transmission
 To prevent HIV transmission, HIV-infected women
in the U.S. should not breast-feed.
 Safe infant feeding alternatives are available.
 ART may decrease free HIV virus in breast milk, but cellassociated virus remains and may pose transmission risk.
 Feeding with premasticated foods may transmit
HIV. Health care providers should routinely inquire
about premastication and
 Instruct HIV-infected caregivers to avoid this
practice, and
 Advise on safer feeding options (AII).
148
August 2015
Long-Term Follow-Up of Infants Exposed to
ARVs (1)
 Data on the long term risks of in utero and neonatal
ARV exposure are insufficient, but the balance of
evidence is reassuring. However, there are
concerns that exposure may have long-term
effects.
 Children with in utero or neonatal exposure to
ARVs who develop significant organ system
abnormalities of unknown etiology, particularly of
the nervous system or heart, should be evaluated
for mitochondrial dysfunction (CIII).
149
August 2015
Long-Term Follow-Up of Infants Exposed to
ARVs (2)
 It is important that the long-term medical record of
an uninfected child includes information about ARV
exposure, should unusual symptoms develop later
in life, or if adverse late effects of HIV or ARV
exposure in uninfected children are identified in the
future.
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AIDS Education and Training Center
National Coordinating Resource Center
APPENDICES
Appendices
 Appendix A. Review of Clinical Trials of
Antiretroviral Interventions to Prevent
Perinatal HIV Transmission
 Includes a table of major studies and results.
 Appendix B. Safety and Toxicity of Individual
Antiretroviral Agents in Pregnancy
 Summarizes and presents available data from
human and animal studies.
 Pharmacokinetics, placental and breast milk
passage, teratogenicity, safety.
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August 2015
ARV Pregnancy Registry (APR)
(1)
 The APR collects observational, nonexperimental
data on ARV drug exposure during pregnancy for
the purpose of assessing the potential
teratogenicity of these drugs.
 It is strongly recommended that health care
providers treating HIV-infected pregnant women
and their infants report cases of prenatal
exposure to ARV drugs to the APR.
 The registry does not use patient names and birth
outcome follow-up is obtained from the reporting
physician by registry staff.
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August 2015
ARV Pregnancy Registry (APR) (2)
 Report cases of prenatal exposure to ARV drugs
(either alone or in combination) to:
ARV Pregnancy Registry
Research Park
1011 Ashes Drive
Wilmington, NC 28405
(T) 1-800-258-4263
(F) 1-800-800-1052
http://www.APRegistry.com
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August 2015
Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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August 2015