Mother to child transmission of HIV

1
Mother to child transmission of HIV

• XIV AIDS Conference Feedback
• July 2002
• Dr Gill McCarthy

2
Effects of HIV on children 2001

• Over 600,000 infants infected with HIV from their
  mothers each year
• 3 million children HIV ve
• 14 million children orphaned by AIDS
• in USA fewer children infected with HIV in one
  year than in one morning in the rest of the world
• childhood mortality in Africa ? - highest in
  Malawi - 25 children die by 5yrs

3
HIV prevalence among pregnant women in major
urban areas ()
4
Reducing mother to child transmission HIV in poor
countries

• WHO strategy the prevention
• new HIV infections in parents to be
• unwanted pregnancies in HIV ve women
• vertical transmission HIV
• Antiretroviral prophylaxis
• modification infant feeding practices
• elective caesarean section is not practical

5
Effects of interventions on rates of mother to
child transmission of HIV
6
MTCT prevention trials
? HIV Tx (mths FU)
delivery
breast fed
66 (18) 50 (6) 26 (24) 30 (15) 60 (1.5) 41
(1.5) NS 47(4) 25(12)
ACTG 076 THAI RETROCI DITRAME PETRA-A PETRA-B
PETRA-C HIVNET 012 (NVP vs AZT)
AZT
AZT 3TC
NVP
NS at 18mth
7
Effectiveness Nevirapine for perinatal HIV
prevention in women with advanced HIV subset
analysis HIVNET 012 (breast feeding)
N 619 1 dose NVP to mum baby vs ip 1 wk pp
AZT
8
Ditrame plus trial short course AZT NVP

• Open label non-randomised trial In Cote dIvoire
  started 3.01- ongoing
• 95 breast feeding
• AZT from 36wks / stat dose AZT 600mg NVP200mg
  in labour / baby AZT 7 days
• interim results compared with Ditrame (AZT only)

9
Vertical transmission HIV at 4 wks AZTNVP vs
AZT
10
Neonatal PEP with NVP AZT in late presenters to
delivery ward

• 1180 babies in Malawi randomised to
• NVP single dose AZT 1wk
• NVP single dose
• FU 12 mth but trial terminated early
• maternal VL is main risk factor
• 50 delivered within 2 hrs
• dosing range 6-24 hr

11
Effectiveness of NVP AZT in neonatal PEP
12
NVP resistance in single dose regimes

• HIVNET 012
• 19 mums developed resistance - K103N (assoc.
  high VL, low CD4 subtype D)
• 46 children (11/24) infected by 6-8wks had
  resistant virus - Y181C (diff. pattern to mum)

Not measured subtype C yet
13
Resistance with different regimes

• Single dose NVP 19 (HIVNET 012)
• Two dose NVP 67 (S. African NVP trial)
• 62 K103N, may be Tx via breast feeding, 78
  revert to wildtype by 1yr
• NVP 3TC (7days) 0

14
Preferential in-utero transmission HIV-subtype C
compared to A or D

• lge cohort study in Tanzania (253 HIV ve babies
  PCR at birth, 6wks, 3mthly)
• 101 subtype A 64 intrapartum
• 73 C 59 in-utero
• 53 D 70 breast feeding
• 22 recombinants 8 early
• 4 unknown 38 late ( 14 unknown)
• Subtype C prevalent in Sub-Saharan Africa -may
  need prophylaxis aimed at in-utero

15
Problems of implementation universal nevirapine?

• How to achieve target of reducing HIV infection
  in children by 50by 2010
• UN pilot sites in 9 African countries providing
  VCT treatment
• only 1/3 HIVve women treated
• only 62 Africans use antenatal care services
• infrastructure unable to cope with VCT etc
• stigma limits uptake testing ,treatment formula
  feeding

16
ARV congenital defects -1

• 100 children born to HIV ve mothers in Mannheim
  (86-01)
• 25 no ARV, 22 AZT, 41 2NRTI, 12 HAART
• 20 congenital malformations (mainly skin
  hernias)
• no difference between treatment gps

17
ARV congenital defects -2

• Antiretroviral Pregnancy Register (89-01)
• prospective reports for 1,970 live births
• prevalence of overall birth defects for 1st
  trimester exposure has remained stable at 2.4
  across all classes of ARV (despite marked changes
  in use of ARVclasses)
• limitations of population data

18
Lactic acidosis in newborns exposed to HIV ARV

• Exposure to NRTIs assoc. with mitochondrial toxic
  effects
• 78 children born to HIVve women (57 Rx AZT).
  All children received AZT
• blood gases lactate levels measured
  prospectively up to 24wks
• 50 hyperlactinaemia, 3 symptomatic, all resolved
  spontaneously by 6mths

19
Infant feeding

• Risk transmission higher in mixed feeding
  compared to exclusive BF or formula feeding at
  3-6mths
• ZEBS trial in Zambia (mortality higher if no BF)
• NVP single dose to mum baby plus abrupt
  weaning at 4mths
• 366 enrolled to date
• 85 achieved exclusive BF by 3-4mths

20
Breast feeding late postnatal transmission HIV

• Individual patient data from 9 RCT in Subsaharan
  Africa to clarify timing determinants
  transmission (BHITS study)
• 4343 mother-child pairs analysed
• 23.1 HIVve children infected by breast feeding
• 31.4 early (lt4wks)
• 23.1 late (gt4 wks with prior -ve test)
• 45 unknown

21
Timing of HIV TX by Breastfeeding

• Cumulative probability LPT
• 6mth 4
• 12mth 9
• 18mth 16
• probability of LPT by duration of BF
• 3mth 10
• 6mth 11
• 9mth 10.1
• 12mth 8.2
• 18mth 4.2

22
Breastfeeding LPT conclusions

• Breastfeeding accounts for 23 HIV transmissions
• at risk throughout breastfeeding period
• transmission risk varies with time (highest at
  7mths)
• geographical variation