Title: Perinatal HIV Prevention: Successes and Challenges in the U.S. and Internationally
1Perinatal 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
2Overview 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
3Update 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.
4Perinatal HIV Transmission Ratesin U.S. Studies
from 1993-2002
5Transmission 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
6Perinatally Acquired AIDS Cases by Year of
Diagnosis, 1981 2002, United States
1000
800
600
400
200
0
7Current 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)
8Specific 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
9General 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
10MIRIAD 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
11MIRIAD 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
12Follow-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
13Conclusions 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?
15International Perinatal HIV PreventionEpidemiolo
gyPEPFAR ActivitiesResearch Success and Plans
16Epidemiology 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
17Baseline Assessment High Antenatal Clinic HIV
Prevalence
14 countries in the Presidents Mother and
Child HIV Prevention Initiative
18The 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
19The 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
20Key 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)
22Key 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
23Operational 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)
-
24Research Addressing Breastfeeding Transmission
25 Breastfeeding Postnatal TransmissionAccounts
for at Least one-third of all Transmissions Among
Breastfeeding Women
26Transmission 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
27Timing 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.
28Summary Estimates of Monthly Risk of HIV
Transmission While Breastfeeding
Late BF Transmission
Early BF Transmission
29Risk 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.)
30South 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
31Early 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
32Prevention 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
33Issues 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
34Recent International Perinatal HIV Trial Results
35International 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
37International Perinatal HIV Trial Results
Early Efficacy at 6 Weeks-4 Mos
1998 Thai Bangkok short AP/IP AZT (no BF) reduction in transmission 50
1998 Ivory Coast short AP/IP AZT (BF) reduction in transmission 37
1999 PETRA AZT/3TC trial (BF) reduction with longest (AP/IP/PP) arm reduction with the IP/PP arm 63 42
1999 Uganda 2-dose IP/PP nevirapine (BF) reduction in transmission 42
2003 Malawi infant NVP vs NVP/AZT (BF) 32
2004 Thailand AZT from 28 weeks plus SD NVP at labor and to newborn 73
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
39Latest 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
40Strategies 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
41Challenges 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
42Summary 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
43Summary 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