HIV Infection and Pregnancy Managing Mother and Baby (PowerPoint by Alexa Chase


									       HIV Infection and Pregnancy
               Managing Mother and Baby

The National Pediatric & Family
HIV Resource Center
University of Medicine & Dentistry
of New Jersey
     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
    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
   300 – 400 babies continue to be born with HIV
    infection each year in the U.S.
    Perinatal Transmission of HIV
   Without antiretroviral drugs during pregnancy,
    mother-to-child transmission has ranged from 16%–25%
    in North America and Europe
   21% transmission rate in the U.S. in 1994 before the
    standard recommendations of zidovudine (ZDV) in
   In 1995, transmission rate was 11% after the change in
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
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)                        1993     1996
       Women diagnosed before giving birth       68 %  81%
       Women offered prenatal ZDV                27 %  85 %
       Women offered intrapartum ZDV              5 %  75 %
       Infants offered neonatal ZDV               5 %  76 %
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 Odds”–1998
     American Academy   of Pediatrics & the American College of
      Obstetricians & Gynecologists–Joint Statement–1999
   USPHS recommendations are under revision
    (coming soon)
   Important: Regulations, laws, & policies about HIV
    screening of pregnant women vary state to state
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   woman’s age, culture, education, and
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
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
    woman’s health and to protect the fetus from acquiring
   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
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 woman’s life
    and prevent HIV transmission to her infant during
   Most women who get the HIV test do not have the virus
   If a woman is HIV+ during pregnancy, she can get
    treatment immediately
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
   Experts recommend that all pregnant women receive an
    HIV test regardless of whether a woman thinks
    she is at risk
 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
 Importance of social support

 Referral for social services
 Collaboration between OB, HIV specialist, and the
  pregnant woman
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
Acceptance of HIV Testing among
Pregnant Women

   IOM reported 75–86% 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
Barriers and Supports to Universal
Prenatal HIV Testing
   Provider’s 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
 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
Timing of Perinatal HIV Transmission
 Casesdocumented intrauterine, intrapartum, and
 postpartum by breastfeeding
     In utero          25%–40% of cases
     Intrapartum       60%–75% 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
Breastfeeding and HIV Infection

 Women  with HIV infection in the U.S. should
 not breastfeed

 Women  considering breastfeeding should know
 their HIV status
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
Maternal Viral Load and Risk of Transmission
Women & Infants Transmission Study (WITS)

HIV-1 RNA          Transmission %            N
  <1000                   0                  0/57
  1000 - 10,000          16.6               32/193
  10,001- 50,000         21.3               39/183
  50,001-100,000         30.9               17/54
  >100,000               40.6               26/64
 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
                Initiate maternal ZDV regardless of
 Recommendation:
 plasma HIV RNA or CD4 counts
What have we learned?
  Interrupting Perinatal HIV Transmission:

  Study Results
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
       Intrapartum
        During labor, 1- hour initial dose 2 mg/kg IV followed by
        continuous infusion of 1 mg/kg until delivery
       Postpartum/Infant Regimen
        2 mg/kg po q 6 hr for 6 weeks, to start 8 – 12 hours after birth
Results of ACTG 076

                       This represents a 66% reduction in risk
                       for transmission (P = <0.001)
        22.6%          Efficacy was observed in all subgroups



        Placebo   ZDV Group
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
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
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
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
Treating Women with HIV
Infection in Pregnancy
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
 When Should an Adult be Treated?
Clinical Category    CD4+ count & HIV RNA          Recommendations
Symptomatic         Any value                      Treat

Asymptomatic        CD4+ T cells <200/mm3          Treat
                    HIV RNA any value
                    CD4+ T cells >200/mm3 but      Offer treatment if pt
                    <350 /mm3, HIV RNA any value   willing to accept
Asymptomatic        CD4+ T cells >350/mm3, HIV     Some experts would
                    RNA >30,000 (bDNA) or          treat
                    >55,000 (RT-PCR)
                    CD4+ T cells >350/mm3, HIV     Many experts
                    RNA <30,000(bDNA) or <55,000   would delay therapy
                    (RT-PCR)                       & observe
Guidelines for Care of All Pregnant
Women with HIV Infection
   Provide standard clinical evaluation – HIV disease stage
   Provide standard immunologic evaluation – absolute 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
    Guidelines for Antiretroviral Drugs in
    Pregnancy: Concepts
   Use optimal ARV for the woman’s 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
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 >1000 (based on most recent VL results)
    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 (<14 weeks)
 If therapy is stopped, stop and restart all ARV simultaneously
 Resistance testing for suboptimal viral suppression or failure
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 48–72 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
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
Assessment of the Pregnant Woman with
HIV Infection
Initial Assessment:
        Desires Antiretroviral Therapy
                 Yes                      No

 Treat according to clinical      Monitor for HIV disease
 & immunologic status             progression

                                               Recommend ZDV
      Wants to  perinatal transmission        Recommend combination
                                               therapy if VL >1000
                                               Discuss C/S
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
Changing HIV Therapy During Pregnancy
   Poor CD4 response
   Drugs with potential teratogenicity
   Poor viral load response
   Poor adherence to regimen
   Evidence of viral resistance
Cesarean Section to Reduce
Perinatal HIV Transmission
   Pregnant women with VL >1000 should be counseled
    re: potential benefit of scheduled C/S to reduce perinatal
   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
   Patient’s decision should be respected and honored
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
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
   Telephone: (800) 258-4263 Fax: (800) 800-1052
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
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
Case Studies
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
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?
 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 a
  C-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?
 Case Study 4
 Heather, 14 weeks gestation, HIV+ for 5 years, stage B2
  (mild dysplasia), CD4+ 220; HIV-1 RNA is 5,000. She’s
  on ZDV, ddI and nelfinavir. She’s 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?
 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
      What should follow-up care include?
 Case Study 6
 Twelve hours after the birth of her infant, Angela G’s
  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?

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