adolescent hiv & pregnancy advanced management & cases

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

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WITS

PACTG2222

111

PACTG1111

222

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WITS

PACTG1111

111

PACTG1111

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%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

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