Motherto Child HIV Transmission: A Thing of the Past

1
Mother-to Child HIV Transmission A Thing of the
Past?

• Jess Fogler, MD
• Assistant Director, Perinatal Hotline
• National HIV/AIDS Clinicians Consultation Center

2
Mother-to-Child TransmissionGlobal Perspective
2005

• 17.5 million women living with HIV
• 6,000 women infected daily
• gt2 million HIV-infected women gave birth
• 2,000 children infected daily
• 2.3 million children living with HIV

Source UNAIDS 2005
3
Mother-to-Child TransmissionGlobal Perspective
2005
Source WHO 2005
4
Incidence of Perinatally-Acquired AIDS United
States, 1985-2000
Reported through December 2000
Slide credit L. Mofenson
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Mother-to-Child TransmissionWhat is the risk?
Risk per episode from known HIV source
6
Mother-to-Child TransmissionUnited States

• Public Health Success Story
• 6,000-7,000 HIV-infected women give birth/yr
• Before 1994 25 transmission
• Today lt2 transmission in U.S.
• Number of infected infants born in U.S./yr
• 2,000 before 1994
• lt300-400 currently

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Mother-to-Child TransmissionUnited States

• Factors leading to reduced transmission
• Enhanced prenatal HIV counseling and testing
• Use of HAART by pregnant women
• Increase in elective cesarean delivery

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How Do AntiretroviralsLower Perinatal
Transmission?

• Effect on viral load
• in mother
• Pre-exposure prophylaxis (PREP)
• of infant (through transplacental AZT passage).
• Post-exposure prophylaxis (PEP)
• of infant (through continued AZT administration
  to the infant after birth).

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Antiretrovirals Should be Given to ALL Pregnant
Women

• AZT lowers transmission even in HIV-infected
  women with very low viral load
• Meta-analysis of 7 prospective cohorts/trials.
• 44 cases transmission among 1,202 HIV women with
  delivery HIV RNA lt1,000.
• Transmission differed by receipt of AZT
• Mothers receiving AZT 8/834, 1.0
• Mothers not receiving AZT 36/368, 9.8

Ioannidis JPA et al. J Infect Dis 2001183
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USPHS Guidelines for Prevention of
Mother-to-Child Transmission

• Women with HIV RNA gt1,000
• HAART during pregnancy
• Elective C/S if gt1,000 near delivery
• PREP and PEP
• Women with HIV RNA lt1,000
• HAART (or use of PACTG 076 AZT alone)
• Vaginal delivery ok if lt1000 near delivery
• PREP and PEP

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Antiretrovirals for Prevention of Mother-to-Child
Transmission

• Antepartum
• Triple therapy preferred
• Including AZT
• NRTIs AZT, 3TC best studied
• PIs SQV, NFV, Kaletra
• Avoid
• EFV (teratogenic)
• NVP (especially if CD4 gt250)
• ddi/d4T combination

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Antiretrovirals for Prevention of Mother-to-Child
Transmission

• Intrapartum
• IV AZT
• Continue other HAART meds

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Antiretrovirals for Prevention of Mother-to-Child
Transmission

• Newborn
• PO AZT for 6 weeks
• Septra PCP prophylaxis
• 6 weeks 4 months

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USPHS Guidelines for Prevention of
Mother-to-Child Transmission

• Women without treatment prior to labor
• Intrapartum-postpartum
• AZT (6 weeks)
• AZT/3TC (one week)
• Single dose NVP
• AZT/NVP
• Infants whose mothers had no treatment prior to
  or during labor
• Infant prophylaxis for 6 weeks with combination
  regimen or AZT alone

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Timing of Mother-to-Child HIV Transmission
(breastfeeding)
Late Postpartum (6-24 months)
Early Postpartum (0-6 months)
Early Antenatal (lt36 wks)
Labor and Delivery
Late Antenatal (36 wks to labor)
0
20
40
60
80
100
Proportion of infections
Slide credit L. Mofenson
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Timing of Mother-to-Child HIV Transmission
(formula)
Early Antenatal (lt36 wks)
Labor and Delivery
Late Antenatal (36 wks to labor)
0
20
40
60
80
100
Proportion of infections
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Importance of the Infant Pre- and Post-Exposure
Prophylaxis
30
27
18
Transmission
15
10
9
6
0
APIPPP IPPP PPlt24 hr PPgt48 hr No AZT
Even When No Maternal AZT Received, Infant AZT
Started Within 24 Hours Reduces Transmission
Wade N et al. N Engl J Med 19993391409
Slide credit L. Mofenson
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HIV Testing for Infants

• HIV antibody tests reflect maternal antibody!!!
• Stays positive for 12-18 months
• Negative antibody test at 18 months definitively
  rules out MTCT
• Dont use cord blood may be contaminated with
  maternal blood

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HIV Testing for Infants

• Current recommendation
• HIV proviral DNA PCR test
• Sens/spec are excellent
• Specificity close to 100 at all time points
• Testing recommended at
• 48 hours (sens 38)
• 14 days (optional for high risk patients sens
  90)
• 1-2 months (sen 96)
• 3-6 months (99.9 sens)

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HIV Testing for Infants

• To rule OUT HIV
• Need two negative viral tests
• One at 1 month or older
• One at 4 months or older
• Confirm with negative ab test at 18 months

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HIV Testing for Infants

• To rule IN HIV
• Confirm a positive virologic test on a second
  specimen ASAP
• HIV infection diagnosed by
• two positive virologic tests on separate samples
  drawn at any age or
• HIVab after 18 months

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Feeding

• Breastfeeding contraindicated in developed world
• Doubles risk of transmission in African studies
• Only recommended if lack of formula or clean water

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Why Hasnt Perinatal Transmission Been Eliminated?

• Continued HIV transmission to women
• especially adolescents
• Lack of prenatal care
• Especially in illicit drug users
• 15 of HIV-infected women lack prenatal care
• Lack of HIV testing
• Antiretroviral drug resistance

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Perinatal HIV TransmissionSan Francisco 1994-2006
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Case from San Francisco

• 30yo health care worker with no HIV risk
  factors
• declined routine HIV screening
• Got plenty of prenatal care
• Delivered healthy-appearing baby
• baby died of PCP a few months later

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What could have been done?

• 2000 40 women who transmitted were not
  diagnosed before delivery

Source CDC
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Opt InOpt Out

• Opt-in, in which each pregnant woman is provided
  with pre-HIV test counseling and must
  specifically consent to an HIV test, usually in
  writing.
• Opt-out, in which each pregnant woman is notified
  that an HIV test will be included in the standard
  battery of prenatal tests (e.g., tests performed
  on all pregnant women), and that she may refuse
  the HIV test.

Source CDC http//www.cdc.gov/hiv/projects/perin
atal/materials/OptOutNew3-2.htm
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Opt InOpt Out

• CDC data from medical records 1998- 1999
• Opt-in approach
• 25-69 consented to HIV testing
• Opt-out approach
• 71-98 consented to HIV testing

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State Laws 2005

• Texas
• Mandatory offering of HIV testing to pregnant
  women OPT OUT
• Oklahoma
• No law

Compendium of State HIV Testing
Laws http//www.ucsf.edu/hivcntr/PDFs/State_HIV_Te
sting_Laws.pdf
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Rapid Testing in Labor

• CDC recommends routine rapid HIV testing for
  women in labor without documented HIV test
• EIA screening test
• Results in lt 1hr
• 99-100 sensitive and specific
• Needs confirmatory Western blot
• Its not too late to intervene!

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Rapid Testing in Labor

• Positive Tests
• Positive predictive value 50 (depending on
  local prevalence)
• Act on all positive rapid tests as true positives
  (until confirmatory test)
• Initiate meds in mom ASAP
• Consider using expanded regimen for mom and
  infant
• Consult local perinatal HIV experts or call the
  Perinatal Hotline [phone]

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Rapid Testing in Labor

• Sounds great but implementation can be difficult
• Requires coordination of health care providers,
  LD, laboratory, hospital administration, risk
  management etc..

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Rapid Testing Resources

• CDC Rapid HIV-1 Antibody Testing during Labor
  and Delivery for Women of Unknown HIV Status A
  Practical Guide and Model Protocol
• http//www.cdc.gov/hiv/rapid_testing/rtlabordeliv
  ery.htmintro2
• http//www.cdc.gov/hiv/projects/perinatal/labor_de
  livery.htm
• Local Trainings (CDC)
• http//www.cdc.gov/hiv/rapid_testing/training.htm
  CalSF

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National Clinicians Consultation Center

• Warmline 800 / 933 - 3413
• National HIV Telephone Consultation Service
• Consultation for clinicians with HIV management
  questions
• PEPline 888 / 448 - 4911
• National Clinicians Post-Exposure Prophylaxis
  Hotline Recommendations on managing occupational
  exposures to bloodborne pathogens
• Perinatal Hotline 888 / 448 - 8765
• National Perinatal HIV Consultation and Referral
  Service
• Advice on managing HIV-infected pregnant women
  and
• HIV testing in pregnancy
• University of California San Francisco
• San Francisco General Hospital
• Supported by
• Health Resources and Services Administration
  (HRSA)
• AIDS Education and Training Centers (AETCs)
• and Centers for Disease Control and Prevention
  (CDC)