Transcript Management of HIV in Pregnancy: A Brighter

Management of HIV in Pregnancy
Iris C. Colón, MD
Associate Chief
Maternal-Fetal Medicine
Dept. of Obstetrics and Gynecology
Santa Clara Valley Medical Center
Case Presentation
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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
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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
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Historical Perspective
Epidemiology
HIV Testing
Standards for Treatment in Pregnancy
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Cornerstones and Goals
HAART
Maternal Evaluation
Outline
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Prevention of Perinatal Transmission
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Pharmaceutical Interventions
Surgical Interventions
Modification of Obstetric Practices
Historical Perspective
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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
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1.2 million living with HIV in the USA in 2009.
– 20% are undiagnosed
– 25% are women
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40,000 new cases in 2009: 10,000 in women
and 166 in children <13 y/o.
Epidemiology
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200,000 women with HIV in the US.
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Majority of infected women are at the peak of
reproduction (14-45 years).
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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
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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
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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
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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
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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
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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
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Pregnancy should not be a barrier to the
most potent HIV therapies.
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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
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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
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Original regimens described in 1996.
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Regimens include 2 nucleoside/nucleotide
RT inhibitors plus a third agent from either
protease inhibitor, non-nucleoside RT
inhibitor, or fusion inhibitor.
HAART
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Nucleoside RT Inhibitors
Zidovudine (ZDV,AZT)*
Lamiduvine (Epivir, 3TC)*
Zalcitabine (ddC, HIVID)
Didanosine (ddi, Videx)
Staduvine (Zerit, d4T)
Abacabir (Ziagen, ABC)
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Nucleotide RT Inhibitors
Tenofovir DF (Viread)
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Fusion Inhibitor
Enfuvirtide (Fuzeon)
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Non-nucleoside RT Inhibitors
Nevirapine (Viramune)
Delavirdine (Rescriptor)
Efavirenz (Sustiva)
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Protease Inhibitors
Indinavir (Crixivan)
Ritonavir (Norvir)
Saquinavir (Fortovase)
Nelfinavir (Viracept)
Amprenavir (Agenerase)
Lopinavir/Ritonavir (Kaletra)*
HAART
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Adherence to therapy is crucial – failure to do
so results in developing resistant virus.
Regimens usually “spare” one class of agent.
HAART: Pregnancy Considerations
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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
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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
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CD4 count <200/mm³ : P. carinni prophylaxis with
sulfamethoxazole/trimethoprim (Bactrim).
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CD4 count <50/mm³ : Mycobacterium avium
complex (MAC) prophylaxis with azithromycin
(Zithromax) and ophthalmology consult.
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Hepatitis C: 33% of HIV patients are coinfected.
Increased risk of liver toxicity from HAART.
Case follow-up
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March:
Viral load 25,823 copies/ml, CD4 count 100
Started on HAART – Lamivudine/Zidovudine (Epivir/AZT) and
Lopinavir/Ritonavir (Kaletra)
Sulfamethoxazole/trimethoprim prophylaxis
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April:
Viral load 103 copies/ml, CD4 count 150
LSIL – Colposcopy multiple condylomatous cervical lesions
Prevention of Perinatal Transmission
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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, 2001–2005, 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
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70-80% at delivery and 20-30% in utero.
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Possible mechanisms:
Microtransfusions during contractions
Ascension through the cervix and vagina during
parturition
Exposure to secretions and blood at delivery
Absorption through infant’s GI tract
Perinatal Transmission
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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
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Pharmacological Interventions
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HAART
ZDV regimen as per PACTG 076 regimen
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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
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Intravenous ZDV is no longer required for
patients receiving combination HAART who
have viral load <400
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Department of Health and Human Services, Panel
on Prevention of Perinatal Transmission 7/31/12
Perinatal Transmission
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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
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Data from these studies was collected prior to
HAART and without data regarding viral load.
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Scheduled cesarean delivery reduces the
likelihood of vertical transmission of HIV
compared with either unscheduled cesarean
section or vaginal delivery.
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Holds true whether or not the patient receives ZDV.
ACOG’s Committee Opinion 2000
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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.
ACOG’s Committee Opinion 2000
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Viral load > 1000 copies/ml – counsel regarding the
potential benefit of scheduled cesarean delivery.
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No reduction in the transmission rate if C/S
performed after onset of labor or rupture of
membranes.
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Patient’s autonomy in deciding the route of delivery
must be respected.
ACOG’s Committee Opinion 2000
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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
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June, July and August:
Viral load <75 copies/ml, CD4 count 120
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August
Vaginal delivery at term
Modification of Obstetric Practices
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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
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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
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Clear infant’s airway with mechanical (not
DeLee) suction.
Remove all maternal body fluids from infant’s
skin immediately.
Clean baby’s skin with soap and water ASAP
and prior to venipuncture, injections and
application of ophthalmic prophylaxis.
Modification of Obstetric Practices
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Breastfeeding is contraindicated in US.
Postpartum care – contraception, pap smear.
Resources for Updated Guidelines
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aidsinfo.nih.gov
hivatis.org
cdc.gov
Summary
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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
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Minkoff H. Human Immunodeficiency Virus Infection in
Pregnancy. Obstet Gynecol 2003;101:797-810.
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Clark W, Lindsay M. Contemporary Management of Human
Immunodeficiency Virus Infection During Pregnancy. The
Female Patient 2002;27:10-16.
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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
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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.
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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
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Minkoff H. Human Immunodeficiency Virus. Creasy/Resnick:
Maternal-Fetal Medicine 1999:725-735.
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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
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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.
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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
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Duff P, Sweet R, Edwards R. Maternal and Fetal Infections.
Creasy/Resnick:Maternal-Fetal Medicine 2009:770-773.