Global Pediatric HIV1 Directions and Challenges

1
Global Pediatric HIV-1 Directions and Challenges

• Grace C. John-Stewart MD, PhD

2
Global Pediatric HIV-1

• Breastfeeding and Transmission of HIV-1
• Treatment of HIV-1
• Prevention of HIV-1
• Programmatic concerns

3
Variable risk of MTCT of HIV (with and without
preventive interventions)
4
(No Transcript)
5
Breastfeeding other issues

• Breast milk nutrition, anti-infectious
• In resource-poor countries - 6-fold increased
  mortality if no BF in first 2 months (WHO)
• Water quality/sanitation, supply of substitutes
• Confidentiality
• Delayed fertility/child-spacing

6
UNAIDS recommendations

• replacement feeding
• when acceptable, feasible, affordable,
  sustainable, safe
• Baby Friendly Initiative and International Code
• exclusive breastfeeding during first mos
• counseling process/guidance
• adequate replacement feeds for 2 years

7
Prevention of breast milk HIV-1 transmission

• No breastfeeding
• Exclusive BF
• HAART during breastfeeding
• ARVs to infant while breastfeeding
• Immunization

8
FF or shortened BF in HIV-1, Cote
dIvoireBecquet, PLoS Medicine 4e17 1-12, 2007.

• 557 children
• 262 were breast-fed (BF)
• 295 formula-fed (FF)
• Formula feeders
• more educated
• less likely to live in shared housing
• more access to tap water in their homes
• 2-year hospitalization or death same among FF
  (14) and short-term BF children (15) (adjusted
  HR 1.19 P 0.44).
• 18-month survival 96 among both BF and FF
  HIV-uninfected children

9
Reality of FF

• when they see me coming with the tins, they
  laugh at me. They say I have HIV (S Africa)
• Counseling
• limited questions on source of water/fuel
• need to boil water
• no demonstrations
• 21/77 non BF infants of HIV-infected women in
  India admitted to hospital versus 0/66 EBF
• health workers are confused and paralyzed on
  what to do about infant feeding (Mickey Chopra,
  Capetown)
• Botswana 2006

10
---- no BF ___ EBF ___ MBF
11
Exclusive BreastfeedingZVITAMBO Study, AIDS
200519699-708

• 2,060 infants LPT (6 wk to 18 mo)
• Practices EBF 7. PBF 24. MBF 69
• Mixed BF 2.6-fold increased HIV-1 risk
• 2/3 LPT 6 mo

12
Exclusive BreastfeedingCoovadia Lancet
20073691107-16

• 1,372 women
• 83 EBF
• 8 FF
• 3 MBF
• EBF definition
• Differences at baseline between groups
• EBF HIV TR 19.5 at 6 months
• Increased risk of HIV with MBF, and risk of
  mortality with FF

13
Realities of EBF

• Intention for EBF but cultural pressure to MBF
• Plans after 6 months?
• Working mothers
• Feeding counseling in general poor 50 planned
  sub-optimal BF (even without HIV)
• Early initiation of BF not promoted in many
  hospital settings, extended maternal/infant
  separation (Durban median 11 hours to first BF)

14
Transmitting mothers have higher HIV-1 levels in
breast milk Rousseau, J Infect Dis
2003187741-7 Rousseau, J Infect Dis, 2004
log10 infected BMC/million
Log10 RNA copies/ml
Scheduled visit
Scheduled visit
15
(No Transcript)
16
Short-course ARVs differ in effect on breastmilk
HIV-1 Chung, AIDS 2005
P
17
Transmitters versus non-transmitters in setting
of short-course ARVsChung, submitted
Transmitter - - -
Non-transmitter ____
18
Breast milk HIV-1 RNA
Plasma HIV-1 RNA
____ HAART .. ZDV/NVP
Compartmental response ZDV/NVP more marked
effect in breastmilk than plasma
19
HAART during breastfeeding

• DREAM Study Mozambique (CROI 2007)
• HAART from 25 wks to 6 months pp
• ZDV, 3TC, NVP or d4T, 3TC, NVP
• Transmission risk 2 at 6 mos
• CDC-Kisumu, KESHO BORA ongoing

20
Infant ARV prophylaxis, SIMBA trialVyankondondera
et al, IATEC 2004www.aidsuganda.org/pdf/PMTCT_SI
MBA_Study.pdf

• ZDV/DDI 36 wk/1 wk pp
• 397 infants, 98 BF
• 199 3TC, 198 NVP
• Transmission risk 6 at birth
• 1
• 1 4 weeks

21
Short postexposure prophylaxis (NVAZ)Taha,
Lancet 2003

• 1,119 mother-infant pairs
• Within 2 hours of delivery
• Randomized
• Infant NVP
• Infant NVP/AZT
• NVP/AZT better than NVP
• 20.9 NVP alone
• 13.3 NVP/AZT

22
CDC-HAART KIBS StudyKisumu, Kenya
GE hospitalizations
Growth failure
Age in months
Age in months
VT Study N440
KiBS N63
Slide courtesy Mary Glenn Fowler and Tim Thomas
23
Immunity in infants

• Repetitive exposure to HIV
• Why do 80 of breastfeeding infants resist
  infection?
• Does early exposure to HIV-1 sometimes immunize?

24
Immunity in infants

• Monoclonal antibodies
• Animal model (2G12, 2F5, 4E10)
• Vaccine studies

Farentelli, J Infect Dis 20041892169-73
25
Progression of HIV-1 in children
26
HIV-1 RNA levels in infants compared to adults
Infants
Adults
27
Pediatric HIV-1 Cohort CharacteristicsObimbo,
Peds Infect Dis 2004
28
Response to ARTWamalwa, JAIDS 2007

• 18 months to 12 years old
• 67 children baseline CD4 5.8
• 67 to
• increased WAZ, HAZ, CD4
• decreased hospitalizations

29
Immunologic response to HAARTD. Wamalwa 2007
18.5
15.8
6.3
n 67
n95
n 43
30
Response to HAART in Kenya D. Wamalwa 2007
6.0
2.5
2.1
2.0
31
Pediatric HIV Mortality

• 1 year mortality
• 35
• Newell 2004
• 40
• Obimbo 2004

Newell Lancet 20043641236
32
Sensitivity of clinical diagnostic testing for
HIV-1Gichuhi, 2006
33
Estimated number of children (infected with HIV, 2005
Eastern Europe Central Asia 2300 1400 3900
Western Central Europe 200 North America 500 East Asia 2300 1000 4100
North Africa Middle East 6900 3200 12 000
Caribbean 3700 2100 5800
South South-East Asia 44 000 23 000 75 000
Sub-Saharan Africa 470 000 370 000 590 000
Latin America 5000 3500 8000
Oceania 1100 400 2800
Total 540 000 (420 000 670 000)
Africa US/Europe 6701
UNAIDS 2005
34
(No Transcript)
35
Implementation strategies to decrease number of
infected infants

• 1,000,000 women, 20 HIV-1, 30 TR
• 10 PMTCT coverage, 15 TR with
• intervention, 30 without intervention
• Increase intervention efficacy 3-fold
• Increase PMTCT coverage 3-fold
• Decrease prevalence in women 2

60,000 57,000 55,000 51,000 48,870
Complex
Simpler
36
Global Pediatric HIV Summary

• More effort to promote prevention of infection
• Early diagnosis challenging
• High early mortality
• Disclosure and adherence issues
• Non-ART interventions important
• Need to remember routine pediatric interventions
• Long-term outcomes
• Adolescence/adults
• Pregnancies

37
Resources

• Women, children and HIV web-site
  (www.womenchildrenhiv.org)
• WHO web-site MTCT
• UNAIDS PMTCT resources
• Elizabeth Glaser (www.pedaids.org)

Josephine Nabukenya More Stories of Hope EGPAF
website