Management of HIV in Pregnancy

Iris C. Coln, MD
Associate Chief
Maternal-Fetal Medicine
Dept. of Obstetrics and Gynecology
Santa Clara Valley Medical Center

Case Presentation
25y/o

Hispanic woman G2P1 at 13+2 weeks

referred for HIV positive result on prenatal
labs.
Prior uncomplicated pregnancy 8 years ago.
New partner with history of drug use.
Pap smear at outside clinic LSIL.

Objectives

Discuss the latest advances in the management of

HIV in pregnancy.
Discuss the risk of mother-to-infant transmission.
Understand current guidelines of antiretroviral
regimens and the modifications during pregnancy.
Promoted obstetric practices that will aid in the
reduction of perinatal transmission.
* I have no conflict of interest disclosures.

Outline
Historical

Perspective
Epidemiology
HIV Testing
Standards for Treatment in Pregnancy

Cornerstones and Goals

HAART
Maternal Evaluation

Outline
Prevention

of Perinatal Transmission

Pharmaceutical Interventions
Surgical Interventions

Modification

of Obstetric Practices

Historical Perspective
June

5, 1981 MMWR
Reports on 5 homosexual men diagnosed
with P. carinii pneumonia.
Subsequently, etiologic agent discovered,
diagnostic tests developed, public health
interventions instituted and pharmaceutical
agents developed.

Epidemiology
1.2

million living with HIV in the USA in 2009.

20% are undiagnosed
25% are women

40,000

new cases in 2009: 10,000 in women

and 166 in children <13 y/o.

Epidemiology
200,000

women with HIV in the US.

Majority

of infected women are at the peak of

reproduction (14-45 years).

African-American

and Hispanic women

account for over 80% of new cases.

Estimates of New HIV Infections, by Race/Ethnicity, Risk

Group, and Gender for the Most Affected US Populations, 2009
Prejean J, et al. Estimated HIV incidence in the United States, 2006-2009. PLoS
One 2001;6(8):1-13. www.cdc.gov

Epidemiology
7,000

pregnancies/yr complicated by HIV in

United States.
Vast majority of pediatric infections are
secondary to vertical transmission.
100-200 infants in the US infected annually.
Many of these infections involve women who
were not tested early enough in pregnancy or
who did not receive prevention services.

Pediatric AIDS (PACTG 076) Trial

Evaluated

safety and efficacy of zidovudine

(ZDV,AZT,Retrovir) vs placebo in HIV
infected pregnant patients.
ZDV during pregnancy and labor, and
neonate for 6 weeks of life.
Reduction of transmission rate from
25% to 8%.

HIV Testing
Serostatus

should be determined as early in

pregnancy as possible.
The Institute of Medicine
Universal HIV testing with patient notification
as a routine component of prenatal care.
ACOG, AAP and the CDC support this
recommendation.

HIV Testing

Why

universal screening?
Attempts to identify those at risk fail to
identify some infected patients.
Avoids stereotyping and stigmatizing.

HIV Testing:
ACOG Committee Opinion 2004

Universal screening via opt-out approach.

Repeat testing in the 3rd trimester to women in areas
of high prevalence, those known to be at high risk for
infection, and those that declined testing earlier.
Use conventional HIV testing in the 3rd trimester.
Use rapid HIV testing in labor for women with
undocumented HIV status.
If rapid HIV test is positive, initiate anti-retrovirals
prophylaxis (with consent).

Standards for Treatment in Pregnancy

Pregnancy

should not be a barrier to the

most potent HIV therapies.

HAART

highly active antiretroviral therapy

Available since 1996 serious side effects
but very effective in reducing viral load and
improving prognosis.

Standards for Treatment in Pregnancy

HAART

is recommended for all pregnant

women to prevent perinatal transmission and
for treatment of maternal HIV disease.
Cornerstones of monitoring : viral loads and
CD4 counts.
The goal in pregnancy is to maintain a viral
load under 1000 copies/ml.

HAART
Original

regimens described in 1996.

Regimens

include 2 nucleoside/nucleotide
RT inhibitors plus a third agent from either
protease inhibitor, non-nucleoside RT
inhibitor, or fusion inhibitor.

HAART

Nucleoside RT Inhibitors
Zidovudine (ZDV,AZT)*
Lamiduvine (Epivir, 3TC)*
Zalcitabine (ddC, HIVID)
Didanosine (ddi, Videx)
Staduvine (Zerit, d4T)
Abacabir (Ziagen, ABC)

Nucleotide RT Inhibitors
Tenofovir DF (Viread)

Fusion Inhibitor
Enfuvirtide (Fuzeon)

Non-nucleoside RT Inhibitors
Nevirapine (Viramune)
Delavirdine (Rescriptor)
Efavirenz (Sustiva)

Protease Inhibitors
Indinavir (Crixivan)
Ritonavir (Norvir)
Saquinavir (Fortovase)
Nelfinavir (Viracept)
Amprenavir (Agenerase)
Lopinavir/Ritonavir (Kaletra)*

HAART
Adherence

to therapy is crucial failure to do

so results in developing resistant virus.
Regimens usually spare one class of agent.

HAART: Pregnancy Considerations

ZDV should be used as component of HAART

regimens.
Overall, nucleoside RT inhibitors well tolerated and
not teratogenic. But avoid staduvine and didanosine
(lactic acidosis).
Efavirenz contraindicated due to teratogenicity in
monkeys and myelomeningoceles in humans.
Indinavir may predispose to nephrolithiasis.
Nevirapine hepatotoxicity.

Maternal Evaluation

Multidisciplinary team approach to care.

Detailed history and physical exam.
Routine prenatal laboratory tests (including STD
screening, Pap smear, PPD).
Hepatitis B and C testing.
Renal and liver function tests.
Viral load
Lymphocyte subset determination (CD4 counts).
Ultrasounds: dating, anatomy, and growth.

Maternal Evaluation

CD4 count <200/mm : P. carinni prophylaxis with

sulfamethoxazole/trimethoprim (Bactrim).

CD4 count <50/mm : Mycobacterium avium

complex (MAC) prophylaxis with azithromycin
(Zithromax) and ophthalmology consult.

Hepatitis C: 33% of HIV patients are coinfected.

Increased risk of liver toxicity from HAART.

Case follow-up

March:
Viral load 25,823 copies/ml, CD4 count 100
Started on HAART Lamivudine/Zidovudine (Epivir/AZT) and
Lopinavir/Ritonavir (Kaletra)
Sulfamethoxazole/trimethoprim prophylaxis

April:
Viral load 103 copies/ml, CD4 count 150
LSIL Colposcopy multiple condylomatous cervical lesions

Prevention of Perinatal Transmission

Vertical transmission is the most common cause of

HIV infection in children - 90% of cases.
Rates vary widely worldwide from 10-60%,
depending on breastfeeding, viral loads and obstetric
practices.
In US 1000 children/yr infected through birth prior
to PACTG 076 regimen.
In the year 2009 down to 131 cases.

AIDS cases due to the perinatal transmission of HIV infection,

by year of diagnosis, 20012005, United States
cdc.gov

Race/ethnicity of children (<13 years) with AIDS diagnosed

during 2005 (includes all children with a diagnosis of AIDS, not
just those who contracted HIV perinatally)
cdc.gov

Perinatal Transmission

70-80% at delivery and 20-30% in utero.

Possible mechanisms:
Microtransfusions during contractions
Ascension through the cervix and vagina during
parturition
Exposure to secretions and blood at delivery
Absorption through infants GI tract

Perinatal Transmission
Supporting

evidence:
Increased infection with increased duration of
ruptured membranes
Reduced rates of transmission with elective
cesarean delivery
Strongest predictor of perinatal transmission:
maternal viral load

Perinatal Transmission
Pharmacological

Interventions

HAART
ZDV

regimen as per PACTG 076 regimen

PACTG 076 Regimen

Timing of ZDV
Antepartum

ZDV Regimen
100mg ZDV PO, 5 times/day,
start 14 wks

Labor & Delivery

IV load dose 2mg/kg, then

continuous 1mg/kg/hr until
delivery

Neonatal

Syrup at 2mg/kg q 6hrs for 6

weeks, start 8-12 hrs after
birth.

Intrapartum ZDV
Intravenous

ZDV is no longer required for

patients receiving combination HAART who
have viral load <400

Department of Health and Human Services, Panel

on Prevention of Perinatal Transmission 7/31/12

Perinatal Transmission
Surgical

Interventions
Data from two prospective studies ( French
and Swiss), an international randomized trial
and a meta-analysis using 15 prospective
cohort studies indicate that there is a
significant relationship between mode of
delivery and vertical transmission.

Perinatal Transmission

Data from these studies was collected prior to

HAART and without data regarding viral load.

Scheduled cesarean delivery reduces the

likelihood of vertical transmission of HIV
compared with either unscheduled cesarean
section or vaginal delivery.

Holds true whether or not the patient receives ZDV.

ACOGs Committee Opinion 2000

Patients should be counseled that in the absence of

antiretroviral therapy, risk of vertical transmission in
25%.
With ZDV, the risk is reduced to 5-8%.
ZDV plus scheduled cesarean delivery, risk reduced
to 2%.
Viral load <1000 copies/ml risk 2% (even without
scheduled cesarean delivery).
No combination of therapies can guarantee a 0%
transmission rate.

ACOGs Committee Opinion 2000

Viral load > 1000 copies/ml counsel regarding the

potential benefit of scheduled cesarean delivery.

No reduction in the transmission rate if C/S

performed after onset of labor or rupture of
membranes.

Patients autonomy in deciding the route of delivery

must be respected.

ACOGs Committee Opinion 2000

Patients should receive IV ZDV, starting 3 hours

preoperatively.
Use prophylactic antibiotics.
Schedule cesarean section at 38 weeks.
Avoid amniocentesis for fetal lung maturity
determination.
Use most recent viral load to direct counseling.

Case follow-up

June, July and August:

Viral load <75 copies/ml, CD4 count 120

August
Vaginal delivery at term

Modification of Obstetric Practices

Determine

HIV serostatus in women who

present in labor with no prenatal care.
Minimize breaks in fetal skin.
Avoid invasive procedures.
Minimize infant exposure to maternal blood
and secretions.

Modification of Obstetric Practices

Forceps

or vacuum extraction: use as

obstetric indications dictate.
Avoid vaginal trauma.
Avoid fetal scalp electrodes and fetal scalp
punctures for pH.
No artificial rupture of membranes (risk of
transmission increases after rupture for 4-12
hours).

Modification of Obstetric Practices

Clear

infants airway with mechanical (not

DeLee) suction.
Remove all maternal body fluids from infants
skin immediately.
Clean babys skin with soap and water ASAP
and prior to venipuncture, injections and
application of ophthalmic prophylaxis.

Modification of Obstetric Practices

Breastfeeding

is contraindicated in US.
Postpartum care contraception, pap smear.

Resources for Updated Guidelines

aidsinfo.nih.gov
hivatis.org
cdc.gov

Summary

HIV screening should be included in the routine panel of

prenatal screening tests for all pregnant women.
Pregnancy should not be a barrier to the most potent HIV
therapies.
The goal in pregnancy is to maintain the viral load at <1,000
copies/ml.
Multidisciplinary team approach to the care of pregnant women
with HIV.
Perinatal transmission rates can be reduced from 25% to 2% if
HIV is detected and treated early in pregnancy.

ONE TEST / TWO LIVES

Questions?

References

Minkoff H. Human Immunodeficiency Virus Infection in

Pregnancy. Obstet Gynecol 2003;101:797-810.

Clark W, Lindsay M. Contemporary Management of Human

Immunodeficiency Virus Infection During Pregnancy. The
Female Patient 2002;27:10-16.

American College of Obstetricians and Gynecologists. Prenatal

and Perinatal Human Immunodeficiency Virus Testing:
Expanded Recommendations. ACOG Committee Opinion No.
304. Washington: American College of Obstetricians and
Gynecologists, 2004.

References

American College of Obstetricians and Gynecologists.

Scheduled Cesarean Delivery and the Prevention of Vertical
Transmission of HIV Infection. ACOG Committee Opinion No.
234. Washington: American College of Obstetricians and
Gynecologists, 2000.

American College of Obstetricians and Gynecologists. Joint

Statement on Human Immunodeficiency Virus Screening.
ACOG Statement of Policy. Washington: American College of
Obstetricians and Gynecologists, 1999, reaffirmed 2006.

References

Minkoff H. Human Immunodeficiency Virus. Creasy/Resnick:

Maternal-Fetal Medicine 1999:725-735.

Connor E, et al. Reduction of Maternal-Infant Transmission of

Human Immunodeficiency Virus Type 1 with Zidovudine
Treatment. Pediatric AIDS Clinical Trials Group Protocol 076
Study Group. N Engl J Med 1994:331:1173-1180

References

American College of Obstetricians and Gynecologists. Human

Immunodeficiency Virus and Acquired Immunodeficiency
Syndrome and Women of Color. ACOG Committee Opinion No.
414. Washington: American College of Obstetricians and
Gynecologists, 2008.

American College of Obstetricians and Gynecologists. Human

Immunodeficiency Virus. ACOG Committee Opinion No. 389.
Washington: American College of Obstetricians and
Gynecologists, 2007.

References

Panel on Treatment of HIV-Infected Pregnant Women and

Prevention of Perinatal Transmission. 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, July 31, 2012.
http://aidsinfo.nih.gov

Duff P, Sweet R, Edwards R. Maternal and Fetal Infections.

Creasy/Resnick:Maternal-Fetal Medicine 2009:770-773.