HIV Infection and Pregnancy Managing Mother and Baby

1

• HIV Infection and Pregnancy Managing
  Mother and Baby

The National Pediatric Family HIV Resource
Center University of Medicine Dentistry of New
Jersey
2

• In collaboration with regional AIDS Education
  Training Centers
• With support from the U.S. Centers for Disease
  Control and Prevention, Cooperative Agreement
  R62/CCR217856-02

3

• Scope of the Epidemic Among Women and Children

• 125,000 AIDS cases in women reported through June
  1999
• AIDS in women has risen from 7 early in the
  epidemic to 24 of adult cases today
• 263 new AIDS cases reported in children in 1999
• 10,000 20,000 estimated children living with
  HIV infection
• 300 400 babies continue to be born with HIV
  infection each year in the U.S.

4

• Perinatal Transmission of HIV

• Without antiretroviral drugs during pregnancy,
  mother-to-child transmission has ranged from
  1625 in North America and Europe
• 21 transmission rate in the U.S. in 1994 before
  the standard recommendations of zidovudine (ZDV)
  in pregnancy
• In 1995, transmission rate was 11 after the
  change in practice

5

• USPHS Guidelines for the Use of Antiretroviral
  Drugs in Pregnant Women for Maternal Health
  Prevention of HIV Transmission

• Developed in 1994 in response to ACTG 076
• Working Group reconvened in December 1999 and
  meets monthly
• Updated recommendations available online at
  HIV/AIDS Treatment Information Service web site
  (www.hivatis.org)

6

• Impact of PHS Guidelines for Reducing Perinatal
  HIV Transmission

• Perinatal HIV transmission has declined sharply
  since the USPHS issued guidelines in 1994,
  resulting in a dramatic decrease in pediatric
  AIDS cases
• 4-State Study Louisiana, Michigan, New Jersey
  and South Carolina (CDC, 1998)
• Women diagnosed before giving birth
• Women offered prenatal ZDV
• Women offered intrapartum ZDV
• Infants offered neonatal ZDV

1993 1996
68 ? 81 27 ? 85 5 ? 75 5 ?
76
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• National Recommendations for HIV Testing of
  Pregnant Women

• Universal testing with patient notification as a
  routine component of prenatal care
• Institute of Medicine (IOM)Reducing the
  Odds1998
• American Academy of Pediatrics the American
  College of Obstetricians GynecologistsJoint
  Statement1999
• USPHS recommendations are under revision (coming
  soon)
• Important Regulations, laws, policies about
  HIV screening of pregnant women vary state to
  state

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• Routine Counseling and Voluntary HIV Testing of
  All Pregnant Women

• Provider Role
• Include HIV prevention education as part of
  routine antenatal care
• Offer HIV testing to all pregnant women
• Provide information on HIV/AIDS
• Consider womans age, culture, education, and
  language

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• Routine Counseling and Voluntary HIV Testing of
  All Pregnant Women

• Provider Role
• Document consent /or decision NOT to test
• Address reasons for not testing and offer again
• Offer the test again for clinical indications
• Provide/refer women with risk behaviors for more
  intensive client-centered prevention counseling

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• Routine Education/Counseling about the HIV Test
  for Pregnant Women

• Content individual counseling, or by brochures,
  videos, group classes
• Cause of HIV/AIDS and how it is spread
• Highly effective treatment is available for the
  womans health and to protect the fetus from
  acquiring HIV
• HIV testing is recommended for all pregnant women
• Services are available to help women from
  becoming infected and to provide medical care and
  other assistance to those who are infected

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• Prenatal Messages for Counseling Pregnant Women
  About the HIV Test

• Anyone can get HIV infection. Women especially
  may not know they are at risk
• HIV is treatable. Treatment can prolong a womans
  life and prevent HIV transmission to her infant
  during pregnancy
• Most women who get the HIV test do not have the
  virus
• If a woman is HIV during pregnancy, she can get
  treatment immediately

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• Prenatal Messages (continued)

• If a woman is HIV negative during pregnancy, she
  can learn ways to prevent getting the infection
  in the future
• All information about HIV testing and the results
  are kept confidential to the extent allowed by
  law. Results may be reportable in your state
• Federal and state laws protect women with HIV
  from discrimination
• Experts recommend that all pregnant women receive
  an HIV test regardless of whether a woman thinks
  she is at risk

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• Counseling the Pregnant Woman with a Positive HIV
  Test Result

• Meaning of the positive test results
• Need for medical management
• Treatment options for her and/or to reduce
  perinatal transmission
• Importance of social support
• Referral for social services
• Collaboration between OB, HIV specialist, and the
  pregnant woman

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• Counseling the Pregnant Woman with a Negative HIV
  Test Result

• Explain the meaning of the negative test results
• Discuss and reinforce risk reduction strategies
• Teach safer sexual practices to help assure she
  continues to be HIV negative

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• Acceptance of HIV Testing among Pregnant Women

• IOM reported 7586 of pregnant women accepted
  voluntary HIV testing
• The IOM reported that evidence demonstrates that
  pregnant women are likely to accept HIV testing
  when it is offered

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• Barriers and Supports to Universal Prenatal HIV
  Testing

• Providers recommendation about testing
• 92.8 were tested if strongly recommended
• 42 if clinician had not recommended
• Private insurance associated with not being
  tested
• Reasons for not being tested
• Not perceiving herself at risk (55.3)
• Having been tested recently (39)
• Test not offered or recommended (11)
• Adverse consequences rarely mentioned

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• Interpreting HIV Test Results

• Standard HIV Serology
• ELISA enzyme immunoassay (EIA)
• Initial screening
• If repeatedly reactive, confirmed by supplemental
  test (Western blot)
• Western Blot confirmatory test
• Optional Testing
• Rapid/Expedited Testing
• Reactive rapid test MUST be confirmed by a
  supplemental test

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• Timing of Perinatal HIV Transmission

• Cases documented intrauterine, intrapartum, and
  postpartum by breastfeeding
• In utero 2540 of cases
• Intrapartum 6075 of cases
• Addition risk with breastfeeding
• 14 ? risk with established infection
• 29 ? risk with primary infection
• Current evidence suggests most transmission
  occurs during the intrapartum period

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• Breastfeeding and HIV Infection

• Women with HIV infection in the U.S. should not
  breastfeed
• Women considering breastfeeding should know their
  HIV status

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• Factors Influencing Perinatal Transmission

• Maternal Factors
• HIV-1 RNA levels (viral load)
• Low CD4 lymphocyte count
• Other infections, Hepatitis C, CMV, Bacterial
  Vaginosis
• Maternal injection drug use
• Lack of ZDV during pregnancy
• Obstetrical Factors
• Length of ruptured membranes/chorioamnionitis
• Vaginal delivery
• Invasive procedures
• Infant Factors
• Prematurity

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• Maternal Viral Load and Risk of Transmission
  Women Infants Transmission Study (WITS)

HIV-1 RNA
Transmission
N
0 16.6 21.3 30.9 40.6
lt1000 1000 - 10,000 10,001- 50,000 50,001-100,00
0 gt100,000
0/57 32/193 39/183 17/54 26/64
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• Maternal Viral Load (VL), ZDV Treatment and the
  Risk of Perinatal HIV Transmission

• Correlation between high maternal VL and
  transmission
• Transmission observed at every VL level,
  including undetectable levels
• No HIV RNA threshold below which there was no
  risk of transmission
• ZDV decreases transmission regardless of HIV RNA
  level
• Recommendation Initiate maternal ZDV regardless
  of plasma HIV RNA or CD4 counts

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What have we learned?

• Interrupting Perinatal HIV Transmission
• Study Results

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• ACTG 076

• A phase III randomized placebo-controlled trial
  of zidovudine (ZDV) for the prevention of
  maternal-fetal HIV transmission
• Treatment Regimen
• Antepartum 100 mg ZDV po 5x day, started at 14
  34 weeks gestation
• IntrapartumDuring labor, 1- hour initial dose 2
  mg/kg IV followed by continuous infusion of 1
  mg/kg until delivery
• Postpartum/Infant Regimen2 mg/kg po q 6 hr for 6
  weeks, to start 8 12 hours after birth

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Results of ACTG 076
30
This represents a 66 reduction in risk for
transmission (P lt0.001) Efficacy was observed
in all subgroups
20
22.6
Transmission Rate ()
10
7.6
ZDV Group
Placebo
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• Follow-up of Uninfected Infants in ACTG 076 ZDV
  versus Placebo

• No significant difference in growth
• No difference in CD4 and CD8 counts between
  groups
• No other safety abnormalities have been
  identified
• No differences in Bayley developmental scores in
  uninfected infants in ACTG 219
• Follow-up of infants with exposure to nucleoside
  analogues is ongoing due to the potential for
  mitochondrial toxicity
• In the U.S. no cases of mitochondrial toxicity
  have been identified

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• Follow-Up of Women in ACTG 076

• Median follow-up 4.2 years
• No substantial differences in CD4 count, time to
  progression to AIDS, or death in women who
  received ZDV compared to those who received
  placebo

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• Reducing Intrapartum HIV Transmission
• Studies of Short Course Therapy

• Oral ZDV in a non-breastfeeding population
  (Thailand) from 36 weeks and during labor
• Transmission rate 9.4 ZDV vs 18.9 placebo
• Petra study intrapartum/postpartum oral ZDV/3TC
  in a breast-feeding population (Uganda, S.
  Africa,Tanzania)
• Transmission rate 10 ZDV/3TC vs 17 placebo
• HIVNet 012 intrapartum/postpartum/neonatal
  nevirapine (NVP) vs short course/neonatal ZDV in
  a breast-feeding population (Uganda)
• Transmission rate 12 NVP vs 21 ZDV

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• Reducing HIV Transmission with
• Suboptimal Regimens

• Partial ZDV regimens (New York cohort)
• Transmission rates
• 6.1 with prenatal, intrapartum, and infant ZDV
• 10 with only intrapartum ZDV
• 9.3 if only infant ZDV started within first 48
  hours
• 26.6 with no ZDV

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Treating Women with HIV Infection in Pregnancy

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• Goals of Antiretroviral Therapy

• To prolong life and improve quality of life
• To suppress HIV to below the limits of detection
  or as low as possible, for as long as possible
• To preserve or restore immune function

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• When Should an Adult be Treated?

Clinical Category CD4 count HIV RNA
Recommendations
Symptomatic Asymptomatic Asymptomatic
Any value CD4 T cells lt200/mm3 HIV RNA any
value CD4 T cells gt200/mm3 but lt350 /mm3, HIV
RNA any value CD4 T cells gt350/mm3, HIV RNA
gt30,000 (bDNA) or gt55,000 (RT-PCR) CD4 T cells
gt350/mm3, HIV RNA lt30,000(bDNA) or lt55,000
(RT-PCR)
Treat Treat Offer treatment if pt willing to
accept Some experts would treat Many experts
would delay therapy observe
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• Guidelines for Care of All Pregnant Women with
  HIV Infection

• Provide standard clinical evaluation HIV
  disease stage
• Provide standard immunologic evaluation
  absolute CD4, CD4
• Provide standard virologic evaluation HIV-RNA
  copy number (viral load)
• Discuss known or unknown risks/benefits of
  therapy during pregnancy
• Develop strategy for long term evaluation and
  management of mother/infant

34

• Guidelines for Antiretroviral Drugs in Pregnancy
  Concepts

• Use optimal ARV for the womans health
• Add ZDV regimen for reducing perinatal HIV
  transmission
• Discuss preventable risk factors for perinatal
  transmission
• Counsel on cesarean delivery
• Support decision-making by woman following
  discussion of known and unknown benefits and
  risks
• Acceptance or refusal of ARV or ZDV should not
  result in denial of care or punitive action

35

• Guidelines for Antiretroviral Drugs in
  Pregnancy Clinical Scenario 1

Women without prior antiretroviral therapy

• Recommend
• Standard combination therapy for women with high
  viral load, low CD4 count
• Combination therapy for women with viral load
  ?1,000 regardless of clinical or immunologic
  status
• 3-part ZDV regimen to reduce perinatal
  transmission for all HIV-infected pregnant
  women, regardless of antenatal viral load
• Consider delaying therapy until completion of
  first trimester
• Offer scheduled cesarean delivery for women with
  viral loads gt1000 (based on most recent VL
  results)

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• Clinical Scenario 2

Women currently on antiretroviral therapy

• Discuss benefits and potential risks of her
  current regimen during pregnancy
• Add or substitute ZDV at ?14 weeks
• Recommend intrapartum and neonatal ZDV
• Discontinue teratogenic drugs
• Consider continuing or stopping current therapy
  based on gestational age (lt14 weeks)
• If therapy is stopped, stop and restart all ARV
  simultaneously
• Resistance testing for suboptimal viral
  suppression or failure

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• Clinical Scenario 3

Women with HIV infection and present in labor
with no previous treatment

• Discuss benefits of treatment during intrapartum
  and neonatal period
• Four treatment options
• Single dose nevirapine for mother at onset of
  labor followed by single dose of nevirapine for
  the newborn at age 4872 hrs
• Oral ZDV/3TC for mother during labor followed by
  one week oral ZDV/3TC to the newborn
• Intrapartum IV ZDV followed by six weeks ZDV for
  the newborn
• The two-dose nevirapine regimen as above combined
  with intrapartum IV ZDV and six week ZDV for the
  newborn

38

• Clinical Scenario 4

Infant whose mother did not receive prenatal or
intrapartum ZDV

• Offer the six-week neonatal ZDV component
• Initiate therapy as soon as possible after
  maternal consent (preferably within 6 12 hours
  of birth)
• Begin diagnostic testing of the infant
• Refer to pediatric HIV specialist for long-term
  care

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• Assessment of the Pregnant Woman with HIV
  Infection

Initial Assessment Desires
Antiretroviral Therapy
Yes
No
Treat according to clinical immunologic status
Monitor for HIV disease progression
Recommend ZDV Recommend combination therapy if VL
gt1000 Discuss C/S
Wants to ? perinatal transmission
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• Follow-Up Assessment of Pregnant Woman with HIV

4 weeks after initiation of treatment, then q 3
months if viral load stable

• Fetal assessment based on gestational age
• CD4 and viral load response
• New onset of symptoms
• Side effects or toxicities
• Adherence to therapy
• Long-range planning for continuity of medical
  care

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• Changing HIV Therapy During Pregnancy

• Poor CD4 response
• Drugs with potential teratogenicity
• Poor viral load response
• Poor adherence to regimen
• Evidence of viral resistance

42

• Cesarean Section to Reduce Perinatal HIV
  Transmission

• Pregnant women with VL gt1000 should be counseled
  re potential benefit of scheduled C/S to reduce
  perinatal transmission
• Unknown whether scheduled C/S offers any benefit
  to women on HAART with low or undetectable VL
  given the low transmission rate
• Complications of C/S similar to HIV uninfected
  women
• Patients decision should be respected and honored

43

• Preterm Labor and the Use of Combination
  Antiretroviral Therapy

• A Swiss study reported a possible association
  between combination ARV therapy and preterm
  births
• Preliminary review of U.S. cohorts has not
  supported the association
• Patients should be educated and cautioned about
  signs of preterm labor

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• Antiretroviral Pregnancy Registry

• A collaborative project managed by PharmaResearch
  Corporation on behalf of an advisory committee
  (specialists in OB/Gyn, ID, teratology,
  epidemiology, and CDC and NIH members) and
  sponsored by
• Abbott Laboratories, Agouron Pharmaceuticals,
  Inc., Boehringer Ingelheim Company, Bristol-Myers
  Squibb, Co., DuPont Pharmaceuticals Company,
  GlaxoSmithKline, F. Hoffmann-LaRoche Ltd., Merck
  Co., Inc.
• Purpose To assess safety of antiretroviral
  drugs during pregnancy
• Telephone [phone] Fax [phone]

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• Comprehensive Care of Women Postpartum

• Primary and HIV specialty care
• Ob/gyn and family planning services
• Mental health and substance abuse treatment as
  needed
• Coordination of care through case management for
  the woman and her family
• Support services for the family

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• Evaluation and Follow up of Infants

• HIV diagnostic testing to establish or rule-out
  HIV infection as early as possible
• Referral to an HIV specialist
• PCP prophylaxis initiated at 6 weeks of age
• Long-term follow-up of HIV- and ARV-exposed
  infants
• Support services for the family

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Case Studies
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Case Study 1

• Angela, 41 y.o., first prenatal visit,
  approximately 19 weeks gestation, tested HIV 2
  months ago. CD4 725, HIV-1 RNA 600 copies/ml.
  This is her 4th pregnancy, she has no children.
• What recommendations for antiretroviral therapy
  apply in this case?
• What questions will you ask what options to
  present?
• What OB condition may complicate this case?
• Follow-up after delivery for the woman and infant

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Case Study 2

• Maria, 27 y.o., at 35 weeks gestation, requested
  HIV test. Former boyfriend died of AIDS. Test is
  positive, CD4 350, HIV-1 RNA 120,000 husband
  and child test negative. Refuses ZDV. It made
  my boyfriend worse. Wants the cocktail that
  Magic Johnson uses.
• What are the recommendations for this woman?
• Psychological issues? Related to community
  beliefs?
• What counseling will you do?

50
Case Study 3

• Ellen, 32 y.o., 9 10 weeks gestation, tested
  positive on voluntary prenatal screening. A
  former heroin user, she is now on methadone. CD4
  198. HIV-1 RNA is 100,000. Under stress. Wants
  HAART therapy and aC-section. Wants to know what
  else she can do to stay well. Heard that
  ritonavir is a good drug.
• What are the recommendations for this woman?
• Screening for other infectious complications?
• Options for reducing perinatal transmission?
• What management issues does this case present?

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Case Study 4

• Heather, 14 weeks gestation, HIV for 5 years,
  stage B2 (mild dysplasia), CD4 220 HIV-1 RNA is
  5,000. Shes on ZDV, ddI and nelfinavir. Shes
  anemic. Husband has AIDS. This is a planned
  pregnancy. Office staff feel this couple is
  irresponsible for having a baby.
• What are the recommendations for this woman?
• What information does this couple need?
• What are other options for this woman? Should she
  be referred?
• How are you going to deal with the office staff?

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Case Study 5

• Joan, G8P3222, HIV for 3 years, admitted with
  ruptured membranes. No prenatal care. Lost 2
  children to HIV. Urine for cocaine, GB strep
  (urine, cervix), other STDs negative. CD4 845.
• What are the recommendations for this mother and
  infant?
• How will you present the 076 regimen to this
  woman?
• What alternative therapies can she choose to
  decrease perinatal transmission?
• What should follow-up care include?

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Case Study 6

• Twelve hours after the birth of her infant,
  Angela Gs HIV test comes back positive. She
  tested negative early in her pregnancy but the
  test was repeated on admission to L D because
  she reported that her husband was back to using
  IV drugs. She did not have any antenatal or
  intrapartum antiretroviral therapy.
• What are the recommendations for this mother and
  infant?
• How will you present the 076 regimen to this
  woman and what are the options ?
• What follow-up care is needed for Angela and her
  baby?