Perinatal HIV Prevention: Successes and Challenges in the U'S' and Internationally

1
Perinatal HIV Prevention Successes and
Challenges in the U.S. and Internationally

• Mary Glenn Fowler, MD, MPH
• Divisions of HIV/AIDS Prevention
• National Center for HIV, STD, and TB Prevention
• November 9, 2004

2
Overview Perinatal HIV Prevention in U.S. and
Internationally

• U.S. Successes and Remaining Challenges
• International Situation
• Epidemiology
• Current and Planned Research Efforts
• Program Activities
• Next Steps and Conclusions

3
Update on U.S. Perinatal HIV Epidemic and
Prevention

• Major progress since 1994 in decreasing perinatal
  HIV in the U.S.
• Before 1994 in the U.S. perinatal transmission
  rates were 20-25
• Now rates of 2 or less can be achieved
• Current estimates are that 6,000-7,000
  HIV-infected women deliver each year
• Status of most are known by delivery
• 10-12 receive little or no prenatal care
• CDC estimates that 280-370 babies continue to be
  infected each year in the U.S.

4
Perinatal HIV Transmission Ratesin U.S. Studies
from 1993-2002
5
Transmission Rates by Type of ARV and OB
Interventions

• AZT alone given prenatally, intrapartum and to
  newborn about 8
• Dual ARVs
• Prenatal AZT/SD NVP 2 non BF 6 BF
• Prenatal/ Intrapartum/Post AZT/3TC 2
• Triple ARVs 2 or less non BF settings
• Scheduled c-section prior to labor onset
  decreases transmission by about 50

6
Perinatally Acquired AIDS Cases by Year of
Diagnosis, 1981 2002, United States
1000
800
600
400
200
0
7
Current CDC Perinatal HIV Prevention Strategies
in the U.S.

• Increase awareness among pregnant women of the
  importance of HIV screening
• Reduce barriers to universal prenatal HIV
  screening support opt out approach
• Promote rapid HIV testing at LD for women whose
  status is still unknown
• Integrate HIV prenatal screening with other MCH
  programs and services that screen for and prevent
  other congenital infections (syphilis, Group B
  Strep, Hep B)

8
Specific CDC Perinatal HIV Prevention Projects
in U.S.

• Since 1999, 10M in Congressional funding per
  year for Perinatal Prevention goes to
• 16 high-prevalence states to support perinatal
  prevention programs
• 10 states for Perinatal HIV Surveillance
  Activities and assessment of states prenatal
  testing rates
• 5 national organizations for development of
  training and education materials
• The MIRIAD study of rapid testing at LD

9
General Types of Perinatal Prevention Programs in
High-Prevalence States

• Social marketing
• Outreach
• Case management high-risk women
• Training of health care workers
• Rapid testing at labor/delivery

10
MIRIAD Study Mother-Infant Rapid Intervention
at Delivery

• CDC supported research in 5 university sites with
  15 related hospitals -- began 1999
• Objectives
• Assess feasibility of offering rapid testing at
  labor/delivery and intervention
• Assess use of rapid test kits for sensitivity and
  specificity
• Assess rates of seroprevalence and transmission
  among late presenting women of unknown HIV status
• Provide linkages to comprehensive care and
  treatment for those women identified by rapid
  testing as HIV-infected, and for their infants

11
MIRIAD Demonstrates Feasibility of Rapid Testing
and Intervening at Labor/Delivery
(Bulterys, et al. JAMA July 2004)

• Between November 2001 June 2003, 69,094 women
  were evaluated at 15 hospital LD units
• Of these, 5,374 (7.8) women were eligible based
  on undocumented HIV status late in pregnancy or
  at labor
• Uptake of rapid testing was 85
• Two thirds of HIV infected women in labor
  received antiretrovirals as did all their
  newborns
• To date 52 HIV women have been detected by rapid
  testing and 4 infants are infected

12
Follow-up Translation Efforts to Support Rapid
Testing at Labor/Delivery

• Recent FDA licensing of rapid tests Oraquick
  and Reveal
• CDC Model Protocol for implementing rapid
  testing at L/D
• Regional trainings on rapid testing in LD
  settings

13
Conclusions U.S. Progress in Perinatal HIV
Prevention

• Dramatic progress in U.S. related to
• Increased uptake of prenatal testing and access
  to rapid testing at LD
• Availability of potent combination ARVs and
  obstetrical interventions including C-section
• Generally adequate public and private health
  care infrastructure
• Feasibility of not breastfeeding in U.S. safe
  water, availability of formula for low income
  women, lack of stigma
• Elimination of any new infant infections is the
  current DHHS/CDC goal

14
Remaining Challenges in the U.S.

• Achieve universal prenatal HIV testing
• Implement rapid HIV testing in labor/delivery
  settings for women whose status is still unknown
• Ensure adequate follow up, comprehensive
  treatment for HIV-infected women
• Develop mechanisms to monitor possible late
  adverse events among ARV-exposed infants
• 70,000 infants have now been exposed to
  perinatal antiretrovirals
• How best to follow up these infants into
  adulthood for potential rare late effects of
  perinatal ARV exposures?

15
International Perinatal HIV PreventionEpidemiolo
gyPEPFAR ActivitiesResearch Success and Plans

16
Epidemiology of Perinatal HIV in International
Settings

• gt95 of HIV-infected children are born in
  resource limited breastfeeding settings
• WHO estimates gt700,000 new infant infections each
  year
• Most all due to mother-to-child transmission
• Transmission rates are generally in 25-40 range
  without antiretroviral interventions
• With antiretroviral interventions, late
  transmission rates at 18-24 months are currently
  15-25
• Maternal HIV seroprevalence up to 35-40 in some
  settings
• Adolescent females are at high risk of infection
• Breastfeeding accounts for 1/3 to 1/2 of all
  transmissions

17
Baseline Assessment High Antenatal Clinic HIV
Prevalence
14 countries in the Presidents Mother and
Child HIV Prevention Initiative
18
The Presidents International Mother and Child
Prevention Initiative

• Announced in June 2002
• 500 million Initiative jointly implemented by
  HHS (CDC and HRSA) and USAID
• Objectives for the Initiative
• Reach up to 1 million women annually
• Reduce mother-to-child HIV transmission by up to
  40 among women treated

19
The Presidents Emergency Plan for AIDS Relief

• Announced January 28, 2003
• Targets 15 countries
• Goals
• Treat 2 million HIV-infected people
• Prevent 7 million new HIV infections
• Provide care for 10 million HIV-infected people
  and AIDS orphans
• Builds upon earlier efforts including the
  Presidents Mother and Child HIV Prevention
  Initiative

20
Key Partners

• Led by the Department of State Global AIDS
  Coordinator
• Ministries of Health
• Nongovermental organizations, faith-based and
  community-based organizations
• Elizabeth Glaser Pediatric AIDS Foundation,
  Columbia MTCT-plus, Family Health International,
  et al
• University partners
• UNICEF/ UNAIDS/ WHO/ World Bank/ Global Fund
• US government agencies Health and Human
  Services, USAID, State Dept, Department of
  Defense, et al

21
PMTCT Core Strategies

• Routine ANC CT
• Simplified pre-test, rapid same-day results
• ARV prophylaxis (2004 WHO guidelines)
• AZT SD NVP
• HAART treatment where feasible and eligible
• SD NVP or short-course AZT
• Screening and prophylaxis in labor
• Infant feeding counseling
• Program support for safe, feasible alternatives
• Family planning, prevention
• Links to care and treatment (e.g., PMTCT)

22
Key CDC Support Roles for PMTCT

• Funding and support for national plans
• Policy and program guidelines
• Strategies / support for scale-up and link to
  care
• PMTCT curriculum and training
• WHO/CDC generic PMTCT curriculum
• PMTCT monitoring system (generic, facility-based,
  local and national monitoring)
• Training guide for routine counseling and testing
• Applied infant diagnosis, program effectiveness
• Program evaluation / operational research

23
Operational Research Program Evaluation in PMTCT

• Integration with MCH programs
• National scale-up and decentralization
• Early infant diagnosis/ program effectiveness
• Use of combination regimens
• Interventions at labor for women of unknown
  status
• NVP resistance implications for treatment
• Linkages to care and treatment (PMTCT)

24
Research Addressing Breastfeeding Transmission
25
Breastfeeding Postnatal TransmissionAccounts
for at Least one-third of all Transmissions Among
Breastfeeding Women
26
Transmission Rates by Feeding Method Nairobi
Randomized Trial (Nduati et al, JAMA 2000 283
1167-74)
40
35
30
25
20
15
10
5
0
Birth
6 wks
14 wks
6 mos
12 mos
24 mos
27
Timing of Breastfeeding Transmission

• Several studies suggest a large proportion of
  breast milk transmission occurs quite early,
  before 1-2 month of age as high as an absolute
  risk of 6 by age 2 months or 3 in months 1 and
  2.
• However, there is then a low continuous risk
  throughout lactation, 0.6-0.8/mo into the
  2nd year of breastfeeding.

28
Summary Estimates of Monthly Risk of HIV
Transmission While Breastfeeding
Late BF Transmission
Early BF Transmission
29
Risk Factors Associated with Transmission
Through Breastfeeding

• HIV viral load in breast milk
• Breast pathology mastitis, abscess
• Type of breastfeeding mixed vs. predominant or
  exclusive breastfeeding (BF)
• Other factors (innate immune factors, vitamin A,
  possibly subtype, HLA etc.)

30
South Africa Vitamin A Trial, Transmission by
Feeding Practice
40
35
30
25
Never BF
20
Excl BF
15
Mixed
10
5
0
1 day
6 mos
15 mos
Infant Age
31
Early BF Cessation Could Prevent a Sizeable
Fraction of Postnatal HIV Infections
68 of all infant postnatal HIV infections
occurred after 6 months ZVITAMBO Study (N2060)
Source Piwoz, Iliff, et al, Bangkok 2004
32
Prevention of HIV Transmission Through
Breastfeeding

• WHO Guidelines for resource-limited settings
• Balances risk of HIV transmission through BF
  with potential increased morbidity and mortality
  associated with not breastfeeding
• Individual counseling
• When acceptable, feasible, affordable,
  sustainable and safe, formula should be used
• Otherwise, exclusive BF with early weaning is
  recommended
• Individual decisions are up to mother

33
Issues Regarding Breastfeeding and HIV in
Resource Limited Settings

• Breast feeding improves overall infant survival
  in resource limited settings
• Safe, feasible and sustainable alternatives to
  breast feeding are not available to most
  HIV-infected women in international resource
  limited settings
• To not breast feed goes against cultural norms
  and may stigmatize a mother or lead to disclosure
  of HIV status
• Decisions on infant feeding are often influenced
  by the father and other family members
• Research is being conducted to determine
  effective strategies that reduce transmission
  risk for HIV women in resource limited settings
  who choose to breastfeed

34
Recent International Perinatal HIV Trial Results
35
International Perinatal HIV Research Trials
Following PACTG 076

• Initial focus on deliverable, prenatal short
  course ARVs in resource-limited settings
• Short course (begun at 36 wks) maternal ZDV
  regimens-Thailand and West Africa
• Combination short course ZDV/3TCPETRA multi-site
  trial in East Africa and South Africa
• SD NVP to mother and newborn--Uganda
• Current and planned trials are now addressing
  transmission during breast feeding
• ARVs to mother or infant during BF
• Immune strategiesvaccines, HIVIG

36
Trial Regimens Shown to Prevent MTCT
IP
AP
PP (baby, mother or both)
3d to 1 wk
36 wks
14 wks
6 wks
28 wks
076
Thai (Harvard)
Thai (Harvard)
Thai (Harvard)
IvC (ANRS), PETRA, Thai (Harvard)
Thai (CDC), IvC (CDC)
PETRA, 012, SAINT
NVAZ

Regimens AZT AZT3TC single dose (SD) NVP
AZT SD NVP
37
International Perinatal HIV Trial Results
Early Efficacy at 6 Weeks-4 Mos
38
Effects of Breastfeeding on Late Perinatal
Transmission Rates
37 No ARV, BF
22.5 AZT AP-IP
20
18.1 AZT/3TC IP-PP
15.7 NVP IP-PP
16.5
14.9 AZT/3TC AP-IP-PP
11.8
8.9
5.7
Infant Age
39
Latest Successful Short-Course International
Trial Results

• Combining ZDV in the last trimester SD NVP at
  labor and to newborn appears highly efficacious
• Thai CDC/TUC results 4.6 if ZDV begun at 34
  weeks SD NVP to mother/newborn
• Thai NIH results 2 if begin ZDV at 28 weeks
  SD NVP
• Ditrame Plus results in BF W. Africa 5.9 with
  combining ZDV from 34 wks SD NVP
• Feb 2004, WHO recommends Short Course ZDV as
  early as possible in the 3rd trimester followed
  by SD NVP regimen at labor onset

40
Strategies of New Trials to Address Breastfeeding
Transmission

• Maternal HAART in last trimester and during 4-6
  months of breast feeding to lower maternal viral
  load
• Infant ARV prophylaxis during first 4-6 months of
  breast feeding
• Exclusive breast feeding followed by early
  weaning at 4-6 months

41
Challenges to Perinatal HIV Prevention U.S. and
Internationally

• Increasing uptake of HIV testing among pregnant
  women, both prenatally and at labor/delivery
• Safety monitoring of ARVs among pregnant women
  and ARV - exposed infants
• Translating perinatal research into deliverable
  sustainable PMTCT programs
• Integrating with other MCH programs
• Using PMTCT as an opportunity gateway for ARV
  treatment and care for HIV affected families
• Assessment of ARVs for PMTCT and their potential
  impact on later treatment options

42
Summary and Conclusions

• There has been major progress in perinatal HIV
  prevention in U.S and international PMTCT
  research, but challenges remain
• PMTCT activities provide a gateway for families
  to access HIV treatment/care

43
Summary and Conclusions

• International issues include breastfeeding
  transmission and health care infrastructure
• Current international research focuses on
  reducing breast milk transmission, resistance
• Primary prevention of HIV infection among
  adolescents and women of child-bearing age is key
  to reducing the perinatal HIV pandemic