Preventing Mother to Child Transmission of HIV: What works, what will

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Preventing Mother to Child Transmission of HIV
What works, what will?

• Amanda J. Gibbons, PhD MPH
• Technical Advisor, MTCT
• Office of HIV/AIDS
• USAID

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(JAMA. 20002831175-1182)
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Timing of MTCT with Breastfeeding and No ARV
Early Antenatal (lt36 wks)
Late Postpartum (6-24 months)
Early Postpartum (0-6 months)
Labor and Delivery
Late Antenatal (36 wks to labor)
5-10
10-20
10-20
Adapted from N Shaffer, CDC
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What the Researchers Have Found
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Factors Contributing to Prenatal and Intrapartum
MTCT

• Biological Factors
• Maternal viral factors
• Membrane rupture, BV
• Chorioamnionitis
• Preterm birth/ low birth weight
• STDs
• Demographic Factors
• Maternal age
• Parity

• Behavioral Factors
• Number of sexual partners during pregnancy
• Frequency of vaginal intercourse
• Polygamy and partner behaviors

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Risk Factors for Postnatal Transmission

• Mother
• Immune status
• Plasma viral load
• Breast milk virus
• Breast infection (mastitis, abscess, bleeding
  nipples)
• New HIV infection
• Viral Characteristics

• Infant
• Breastfeeding duration
• Non-exclusive BF
• Age (first months)
• Lesions in mouth, intestine
• Prematurity
• Infant immune response

WHO, 1998 Bulterys et al, 2002 Newell et al,
2002
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How Does HIV Transmission During Breastfeeding
Occur?

• Exact mechanisms unknown
• HIV virus in blood passes to breast milk
• cell-free, cell-associated virus observed
• virus shed intermittently (undetectable 25-35)
• levels vary between breasts in samples taken at
  same time (Willumsen, 2001)
• Infant consumes HIV
• enters/infects through permeable mucosal
  surfaces, lymphoid tissues, lesions in mouth,
  intestine
• Although BF infant may consume gt500,000 virons,
  gt25,000 infected cells per day, majority dont
  become infected (Lewis, 2001)
• immune factors in BM may play a role (Sabba et
  al, 2002)

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Elements To Reduce MTCT
ARV Prophylaxis
Early cessation
Interventions
Use of breastfeeding alternatives/ Exclusive
breastfeeding (?)
HIV Testing/ Counseling Prevention of Infection
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Comparison of Five ARV Prophylaxis Trials

• RETRO-CI and DITRAME pooled results (ZDV vs.
  placebo)
• HIVNET012 (NVP vs. AZT)
• Kenya study (formula vs. breastfeeding)
• PETRA (ZDV/3TC regimens)
• SAINT (NVP vs. ZDV/3TC)
• (Nolan, AIDS 2002)

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MTCT at 6 Weeks for 5 Studies
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Post-Exposure Prophylaxis Studies

• In Malawi (n1059)
• NVP single dose (2 mg/kg)
• NVPZDV (4 mg/kg, 2x/day for 7 days)
• all breastfeeding

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Infant Post-Exposure Prophylaxis with NVPZDV (7
d) vs NVP Only - Malawi (Taha et al ThOrD1427))
NVPZDV reduced HIV transmission in first 6 wks
(plt0.01), and improved HIV-free survival at 18 mo
(61 vs 42)
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Implementing Research Findings
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Programming to Reduce MTCT

• Prevention programs
• Safe Obstetric Practices
• Antiretroviral Prophylaxis
• Safer Infant Feeding
• Family Planning
• Partner Involvement

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WHO Strategic Approach to Reducing MTCT

• Preventing HIV infection, especially in young
  women
• Preventing unintended pregnancies in HIV women
• Providing antiretroviral drugs to all pregnant
  HIV women and counseling on feeding options

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WHO Approach
Possible Interventions
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WHO Approach
Possible Interventions
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MTCT Challenges in Implementing Research Findings

• HIV counseling and testing
• ARV prophylaxis
• Infant feeding
• Care and treatment
• Country protocols and policies
• Comprehensive program for mothers, infants, and
  family

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HIV Counseling and Testing The Entry Point for
MTCT Services

• Uptake influenced by
• Level of education
• Partner testing
• (C Vwalika, TuPeD4983 )
• Approaches to HIV counseling and testing in ANC
• Opt-in
• Opt-out
• Mandatory, Universal

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ARV Prophylaxis

• Which regimen to use?
• Packaging of medication is for theraputic Rx
• Home deliveries/TBAs
• Adequate and trained staff
• Confidentiality

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ARV Regimens in the Field

• NVP single dose
• Short-term ZDV prophylaxis
• Resistance issues?
• New regimens?
• Post exposure prophylaxis?
• Future regimens, HAART?

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Infant Feeding Choices

• Exclusive breastfeeding vs. mixed feeding
• Infants exclusively breastfed for 3 months or
  more had no excess risk of HIV infection over 6
  months than those never breastfed (Coutsoudis,
  South Africa)
• Breastfeeding vs. formula feeding
• HIV-1-free survival at 2 years was significantly
  higher in the formula arm than the breastfeeding
  arm. Two-year estimated mortality rates among
  infants were similar in both arms (Nduati, Kenya)
• Results from further studies, HAART, the future?

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WHO Recommendations on Infant Feeding for HIV
Women

• When replacement feeding is acceptable,
  feasible, affordable, sustainable and safe,
  avoidance of all breastfeeding by HIV-infected
  mothers is recommended.
• Otherwise, exclusive breastfeeding is
  recommended during the first months of life.
• To minimize HIV transmission risk, breastfeeding
  should be discontinued as soon as feasible,
  taking into account local circumstances, the
  individual womans situation and the risks of
  replacement feeding (including infections other
  than HIV and malnutrition).
• New Data on the Prevention of Mother-to-Child
  Transmission of HIV and their Policy
  Implications Conclusions and Recommendations
  (WHO 2001)

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UNGASS goals for PMTCT

• by 2005, HIV infants reduced by 20
• by 2010, HIV infants reduced by 50

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Reaching UNGASS Goals (K Reilly/WHO)

• Reaching 2005 goal (20 reduction) requires
• 90 ANC coverage
• 70 VCT acceptance
• 75 ARV acceptance/correct use
• Reaching 2010 goal (50 reduction) requires
• 100 for all the above
• Reality is that total coverage lt 20 (ARV
  prophylaxis)

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Integration of MTCT and other Health Care Services

• Safe motherhood programs
• Family planning
• IMCI/child survival
• Care and Support

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MTCT Plus

• Care and Support for mothers, infants, and family
• HAART, Rx for opportunistic infections
• Infrastructure for postnatal care
• Home-based care
• What pediatric AIDS care is available?

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Need to Scale-Up MTCT Programming Beyond Pilot
Stage
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Implementation Issues

• Political commitment
• Health care infrastructure and human resources
• Partnerships and collaboration
• Large numbers of staff to be trained
• HIV counseling overwhelming MCH providers
• Complex infant feeding guidelines
• Getting women to come back
• Evolving research issues!!

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Provision of Interventions to Prevent MTCT,
Lusaka, Zambia
Mar, 2000 Mar, 2002
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Factors Affecting Uptake of Interventions to
Prevent MTCT

• Fear of positive result
• Stigma
• Confusion over infant feeding choices
• Lack of male involvement
• Community norms and understanding of issues

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President Bushs International Mother and Child
HIV Prevention Initiative

• Increasing Preventive Treatment and Care
• Administering HAART to mother and treating mother
  and infant following birth (where infrastructure
  exists)
• Administering a single dose of nevirapine to the
  mother at time of delivery and at least one dose
  to infant shortly after birth (where
  infrastructure does not exist)
• Supporting safer infant feeding practices

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President Bushs International Mother and Child
HIV Prevention Initiative

• Building Healthcare Delivery Systems
• Hospital/clinics twinning
• Volunteer medical and nursing training corps
• Supporting NGOs and governments to help expand
  existing activities and create new public-private
  partnerships aimed at significantly reducing MTCT
  and helping families

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Outstanding Issues in MTCTNeed for Further
Research

• Infant feeding, including formula feeding, early
  weaning
• NVP resistance
• New ARV prophylactic regimens
• Effect of subtype on transmission
• Operations Research

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The Future

• HAART to prevent MTCT
• President Bushs Emergency Plan for AIDS Relief
• Prevent 7 million new infections (60 percent of
  the projected 12 million new infections in the
  target countries)
• Provide antiretroviral drugs for 2 million
  HIV-infected people and
• Care for 10 million HIV-infected individuals and
  AIDS orphans.
• Vaccine
• Male circumcision (MTCT -)