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8/4/2019 Adolescent HIV & Pregnancy Advanced Management & Cases
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Disclosure of Financial Relationships
This speaker has no significant financial relationships withcommercial entities to disclose.
This slide set has been peer-reviewed to ensure that there are
no conflicts of interest represented in the presentation.
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Objectives
Discuss similarities & differences between pregnancycourse & outcomes in vertically & horizontally infected
adolescents
Consider effective implementation of strategies to
prevent perinatal HIV transmission in pregnantadolescents
Compare the risks of & benefits of vaginal delivery &
CS in HIV infected pregnant adolescents
Provide advanced discussion of management ofspecific aspects of care in HIV infected pregnant
adolescent
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Adolescent Pregnancies
400,000 deliveries/yr in USA
PTL
Anemia Hypertensive disorders
LBW
NND
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HIV Infected Adolescents
Adolescents aged 13-19 years with HIV/AIDSin USA n=5678
STIs 12% and abnormal cervical cytology
47.5% PACTG 219C
Case report 1998
Case series MMWR 2002
Case series AJOG 2009
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Reproductive Health of
Adolescent Girls Perinatally
Infected with HIV 47.5% had abnormal cervical cytology
Sexually active girls less likely to be on ART
than non sexually active girls
Condyloma & trichomonas most frequent genital
infections
Brogly 2007
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Reproductive Health of
Adolescent Girls Perinatally
Infected with HIV 17% experienced a first pregnancy by age 19
years
7 had additional pregnancies
32 live births
All received ART in pregnancy
PNT rate 3.3%
Brogly 2007
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HIV Infected Women Delivering at
UM/JMH Medical Center
2005 2006 2007 2008 2009 2010
Womendelivered
139 146 153 148 122 90
VL
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Adolescent Pregnancies 2010:
The Miami Experience
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Perinatal Infection & Pregnancy
Outcomes: The Miami Experience
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Preconceptional Counseling:
Recommendations
Discuss reproductive options
Assess pregnancy intentions on ongoing
basis
Refer to experts
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Preconception Counseling Impact of HIV on pregnancy, pregnancy on HIV
progression, ARV treatment on pregnancy
Maternal risk factors: drug/alcohol use, comorbid
conditions
General pregnancy issues Guardianship issues
Risk, prevention of perinatal transmission
Discussion of assisted reproductive technologieswith the HIV-treating provider and the OB/GYN
Adapted from: Anderson J. A Guide to the Clinical Care of Women With HIV/AIDS. 2005.Chapter VII
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Offer effective and appropriatecontraceptive options to reduce likelihood
of unintended pregnancy
Be aware of potential interactions with
ART which could lower efficacy
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NNRTI and Hormonal Contraceptives
ART Effect on Drug
Levels
Clinical
commentEfavirenz EE 37% Clinical significance
unknown
Etravirine EE 22%NE no significanteffect
No dosageadjustmentnecessary
Nevirapine EE 20%NE 19%Depo no change
Use alternative oradditional methods
No dosageadjustment needed
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Ritonavir Boosted PI & Hormonal
Contraceptives
Atazanavir EE Norgestimate
Minimum dose 35 mcg
EE
Darunavir EE 44%
NE 14%
Use alternative or
additional method
Fosamprenavir EE 37%NE 34%
Use alternative oradditional method
Lopinavir EE 42%
NE 17%
Use alternative or
additional method
Saquinavir EE Use alternative oradditional method
Tipranavir EE 48%
NE no change
Use alternative or
additional method
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PI Without Ritonavir & Hormonal
Contraceptives
Atazanavir EE 48%
NE 110%
Max 30mcg EE
Fosamprenavir EE
NE
Amprenavir 20%
Use alternative
Indinavir EE 25%
NE 26%
No dose adjustment
Nelfinavir EE 47%
NE 18%
Use alternative or
additional method
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CCR-5 Antagonist & Hormonal
Contraceptives
Maraviroc No significant effecton EE or
levonorgestrel
Safe to use in
combination
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Educate and counsel about risk factors forPNT
Strategies to reduce those risks
Potential effects of HIV or treatment onpregnancy course and outcomes
Advise re breastfeeding
Mother to Child HIV Transmission
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Mother to Child HIV Transmission
in the U.S.
. %11
. %11. %11. %11
. %11
. %222
1
11
11
11
11
1111
WITS
PACTG2222
111
PACTG1111
222
1111
WITS
PACTG1111
111
PACTG1111
111
%Transm
ission
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Possible Routes of
Transmission
In-utero At Birth During Breastfeeding
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Risk Factors for Transmission
in Era of Antiretroviral Therapy:
Viral Load
Type of Antiretroviral Therapy
Mode of Delivery
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Delivery VL & Perinatal Transmission
%1%1
%11
%11
%11
1
11
11
11
11
%Trans
mission
111111
Delivery Plasma HIV RNA
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Perinatal HIV Transmission andMaternal HIV RNA Viral Load
Correlation between maternal VL and risk oftransmission even in pregnant women treatedwith ARV agents
Risk of transmission with VL ND is extremelylow but transmission has occurred at all VLlevels
ZDV decreases transmission regardless of VLlevel
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Consider when prescribing ART effectivenessfor treatment of HIV
Hepatitis B status
Potential for teratogenicity should pregnancyoccur
Possible adverse outcomes for mother and
fetus
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Use preconception time period for adjustmentof ART regimens to exclude efavirenz or
other drugs with teratogenic potential for
women contemplating pregnancy
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For adolescents who are on ART for their ownhealth and who want to get pregnant, set
attaining a stable maximally suppressed
maternal viral load prior to conception as a
primary treatment goal for her own wellbeingand to decrease risk of MTCT
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Evaluate and appropriately manage therapyassociated side effects that may adversely
impact maternal fetal health outcomes eg
hyperglycemia, anemia, hepatotoxicity
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Evaluate need for appropriate prophylaxis ortreatment for OIs including safety, tolerability
and potential toxicity of specific agents when
used in pregnancy
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Antepartum Care
Review of prior HIV related illnesses, CD4counts, VL & resistance studies
Current CD4 count & VL
Assess need for OI prophylaxis
Baseline CBC, renal & liver profiles
Hx prior ART
Immmunizations
PPD
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Effects of ARV in Pregnancy
Pregnant woman
Fetus
Newborn
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FDA Pregnancy CategoriesA Adequate well-controlled studies of pregnant women fail to
demonstrate a risk to the fetus during first trimester (no evidence
exists of risk during later trimesters).B Animal reproduction studies fail to demonstrate a risk to the fetus,
and adequate but well-controlled studies of pregnant women have
not been conducted.C Safety in human pregnancy has not been determined; animal
studies are either positive for fetal risk or have not been conducted,and the drug should not be used unless the potential benefit
outweighs the potential risk to the fetus.D Positive for human fetal risk that is based on adverse reaction data
from investigational or marketing experiences, but the potential
benefits from the use of the drug among pregnant women might beacceptable despite its potential risks.
X Studies among animals or reports of adverse reactions haveindicated that the risk associated with the use of the drug for
pregnant women clearly outweighs any possible benefit.
ART S f t D i P
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ART Safety During Pregnancy
B C D
NRTIs Didanosine
Emtricitabine
Tenofovir
Abacavir
Lamivudine
Stavudine
ZidovudineNNRTIs Etravirine
Nevirapine
Delavirdine Efavirenz
Protease inhibitors Atazanavir
Darunavir
Nelfinavir
RitonavirSaquinavir
Amprenavir
Fosamprenavir
Indinavir
Lopinavir/rTipranavir
Entry inhibitors Enfuvirtide
Maraviroc
Integrase inhibitor Raltegravir
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Antiretroviral Agents in Pregnancy
NRTI NNRTI ProteaseInhibitor EntryInhibitor IntegraseInhibitor
Recommended Zidovudine
Lamivudine
Nevirapine Lopinavir/r
Alternate Didanosine
EmtricitabineStavudine
Abacavir
Atazanavir
IndinavirNelfinavir
Saquinavir HGC
Insufficient data Tenofovir Efavirenz
Etravirine Darunavir
Fosamprenavir
Tipranavir
Enfuvirtide
Maraviroc
Raltegravir
Not
recommended
Delavirdine
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Prevalence of Birth Defects After
First-Trimester Exposure to ART
.11 .22
.11
.22.11
.22
.11
.
11
.11
.
11
.
11
1
1
1
1
1
1
1
Incidence(%livebirths)
Registry Coordinating Center. The Antiretroviral Pregnancy Registry Interim Report,December 2007. http://www.apregistry.com/forms/interim_report.pdf. Accessed April 9, 2008.
I f t T i iti & ARV
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Infant Toxicities & ARV
Exposure
Potential for mutagenic and carcinogenic effects mitochondrial dysfunction
Zidovudine-related infant toxicity: anemia HIV-negative infants exposed in utero &
neonatally have lower hematologic
measurements than unexposed infants
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Special Considerations for ARV Useby Pregnant Women and Infants
Pregnancy may alter ARV absorption,distribution and metabolism
ARV dosing and toxicity risk may be affected
Some PIs may require altered dosing
Limited data to guide treatment in pregnant
women
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Pregnancy Post Partum1
11
11
11
11
111
111
LPVAUC
(mcg*hr/mL)
Lopinavir Exposure
th percentile11
th percentile11
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Special Considerations for ARV Useby Pregnant Women and Infants
Potential adverse effects in pregnancy includingteratogenicity
Avoid during pregnancy:
Efavirenz possible risk of NTDsNelfinavir potential teratogenicity of ethyl methanesulfonate
Tenofovir bone abnormalities in animal studies
Combination of d4T + ddI increased risk of lacticacidosis and hepatic steatosis
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Special Considerations
Use with caution during pregnancy:
Nevirapine increased risk of hepatotoxicity; do notinitiate in women with CD4 cell count >250 cells/mm3
NRTIs: risk of lactic acidosis/hepatic steatosis; monitor
LFTs, electrolytes monthly in 3rd trimester; assess oftenfor new symptoms
Screen for hyperglycemia:
Standard glucose loading test at 24 -28 weeks
Consider earlier screening if on chronic PI-basedtherapy
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ART and Pregnancy Outcome
Conflicting data: are ARVs associated with adverse
outcomes, especially PTD? Most U.S. data do not demonstrate increasedrisk
Conflicting data: does in utero ARV exposurecause mitochondrial dysfunction in neonates?
If true, appears to be very rare
HIV-infected women should receive combinationARV therapy according to current guidelines
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Adverse Pregnancy Outcome
Combination therapy was
associated with a 33% risk of
premature delivery
Lorenzi et al, AIDS 1998
Ad P O t
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Adverse Pregnancy Outcome
No increase in preterm delivery,
low birth weight or stillbirth
5% on PI versus 2% had VLBW
Tuomala et al, NEJM 2002
Pregnancy Outcomes by ARV
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Pregnancy Outcomes by ARV
RegimenCombination vs monotherapy
Combination: PI vs no PI
Any ART vs none
Adjusted Odds Ratio (95% CI)
Preterm birth
(37 weeks)
Low birth
weight
(
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ART & Risk of PTD
Combination therapy with a PI isassociated with an increased rate of
preterm delivery (p=0.0001)
OR 2.4, 95% CI 1.3 - 4.4
Cotter et al. JID 2006; 193: 1195
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Intrapartum Carefor HIV-Infected
Women
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Intrapartum ART/Prophylaxis
IV ZDV recommended for all HIV+ womenduring labor
Continue other ARVs orally on schedule as possible
When administering ZDV, discontinue d4T
If suboptimal VL suppression on ARV,single-dose intrapartum maternal + infantNVP not recommended
Cesarean delivery if VL >1,000 copies/mL
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Women with ZDV resistance should receiveIV ZDV during labor, along with their ARVregimen
Their infants should receive oral ZDV for 6 weeks
Often, only wild-type virus is transmitted
ZDV crosses placenta readily, with high levels infetus
Reduces genital HIV VL
Consult pediatric HIV specialist
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C D li t R d
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Cesarean Delivery to Reduce
Perinatal HIV Transmission
Unclear whether scheduled C/S offers anybenefit to women on ART with VL
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Maternal Risks by Mode of Delivery
Counsel women about potential risks and benefitsof cesarean vs vaginal delivery
C/S associated with greater risk of complications
Complications do not outweigh benefits of reducedHIV transmission for those at increased risk
Prophylactic narrow spectrum antibiotic generallyrecommended at time of C/S
HIV-Infected Newborns 2005-2010HIV-Infected Newborns 2005-2010SANTA ROSA
OKALOOSAHOLMES
JACKSON
ESCAMBIA
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MADISON
TAYLOR
JEFFER
SONWALTON
WASHINGTON
CALHOUNBAY
GULF
GADSDEN
LIBERTY
FRANKLIN
LEON
WAKULLA
HAMILTON
SUWANNEE
LAFAYETTE
DIXIE
COLUM
BIA
GILC
HRIST
LEVY
ALACHUA
PUTNAM
MARION
LAKECITRUS
SUMTER
HERNANDO
BAKER
NASSAU
DUVAL
CLAYST JOHNS
FLAGLER
VOLUSIA
SEMINOLE
ORANGEBREVARD
OSCEOLA
PASCO
HILLSBOROUGHPOLK
MANATEE
HARDEE
HIGHLANDS
PINELLAS
UNION
INDIAN RIVER
OKEECHOBEE
ST LUCIE
MARTIN
PALM BEACH
BROWARD
DADEMONROE
COLLIER
HENDRYLEE
CHARLOTTEGLADES
DESOTOSARASOTA
2007 Births
(15)
(17)
(10) 2008 Births
(17)
2009 Births
(8)
(6) 2010 Births
2005 Births
2006 Births