Associate Chief
Maternal-Fetal Medicine
Dept. of Obstetrics and Gynecology
Santa Clara Valley Medical Center

 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.

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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.

 Historical Perspective
 Epidemiology
 HIV Testing
 Standards for Treatment in Pregnancy
– Cornerstones and Goals
– HAART
– Maternal Evaluation

 Prevention of Perinatal Transmission
– Pharmaceutical Interventions
– Surgical Interventions
 Modification of Obstetric Practices

 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.

 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.

 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

 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.

 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%.

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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.

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

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Universal screening via opt-out approach.
Repeat testing in the 3 rd 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 3 rd 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).

 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.

 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.

 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.

 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)*

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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.

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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.

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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.

 CD4 count <200/mm ³ : P. carinni prophylaxis with sulfamethoxazole/trimethoprim (Bactrim).
 CD4 count <50/mm ³ : 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.

 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

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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

 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 infant’s GI tract

 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

 Pharmacological Interventions
 HAART
 ZDV regimen as per PACTG 076 regimen

Timing of ZDV
Antepartum
Labor & Delivery
Neonatal
ZDV Regimen
100mg ZDV PO, 5 times/day, start 14 wks
IV load dose 2mg/kg, then continuous
1mg/kg/hr until delivery
Syrup at 2mg/kg q 6hrs for 6 weeks, start 8-12 hrs after birth.

 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

 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 .

 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.

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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.

 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.
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Patient’s autonomy in deciding the route of delivery must be respected.

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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.

 June, July and August:
Viral load <75 copies/ml, CD4 count 120
 August
Vaginal delivery at term

 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.

 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).

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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.

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

 aidsinfo.nih.gov
 hivatis.org
 cdc.gov

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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

 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.

 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.

 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

 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.

 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.