Advantages and risks for a child to be exposed to the triple prophylaxis during pregnancy and breastfeeding What is the best for the child ?

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Advantages and risks for a child to be exposed to
the triple prophylaxis during pregnancy and
breastfeedingWhat is the best for the child ?

• Pr C. Courpotin

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What is the best for the child?

• Not to be HIV infected
• If infected to be treated as soon as possible
• This suppose
• Undetectable VL in mother during pregnancy
• Access to early diagnosis (PCR)

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PMTCT and triple prophylaxis

• Most protocols include triple therapy from 28
  weeks to. 6 months if the child is breastfed
• WHO 2006 . AZT monotherapy from 28 w to delivery
  and then NVP, AZT,3TC
• Triple prophylaxis should be proposed starting
  from 28 weeks until 6 months if breast feeding

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PMTCT and triple prophylaxis

• Child is exposed to ARV at two different periods
  through two different mechanisms
• During pregnancy (transplacental transfer)
• During breast feeding (through breast milk)
• Which prophylaxis ?
• AZT 3TC EFV
• Or ?

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Advantages of triple prophylaxis for the child

• During the whole process (pregnancy
  breastfeeding)
• low and efficient PMTCT
• During breastfeeding it allows
• Respect of breastfeeding
• Nutritional advantages
• Immunological advantages
• Respect of cultural practices
• Decreased stigmatization for the mother

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Benefits of breast feeding with triple prophylaxis

• Low risk of transmission
• Amata study 1.6 (0.6 BF)
• Mitra plus study 5 ( 0.9 BF)
• Kisumu breast feeding study 5.9 (3.5 BF by
  12 months)

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Risks of triple prophylaxis for the child

• During the whole process (pregnancy
  breastfeeding)
• Persistent risk of MTC transmission even if very
  low (lt 1 on 6 months)
• Risk of ART toxicity (placental and breast milk
  transfer)
• Risk of acquired resistances and impact on future
  treatment in case of contamination

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Is there a risk of toxicity in breastfed children
with mother on ART ?
CROI 2008 abstract 72 M.Mirochnick et al

• Analysing 45 plasma, 35 breast milk and 42 DBS
  obtained from 15 infants-mothers pairs with
  mother receiving AZT 3TC NVP (Kisumu
  breasttfeeding study / Uganda) it appears that
• In BM
• ZDV low concentrations
• 3TC concentrates in BM ( gt plasma)
• NVP concentrates in BM ( gt 3400 ng/ml
  therapeutic drug monitoring program in some
  children (risk of potential drug toxicity,
  partial HIV suppession and development of drug
  resistance)

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Is there a risk of acquired resistance in the
child ?

• Yes through 2 mecanisms
• Transmisssion of a resistant virus
• Acquired resistance due to ARV concentration in
  breast milk

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Child and triple prophylaxis during pregnancy and
breast feeding

• Balance beetween benefits and risks
• Low transmission vs acquired resistances
• No life (80 mortality within 2 years) against
  life with.

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Triple prophylaxis and late coming of the mother
or incomplete protocols

• Mothers VL should be undetectable at the time of
  the onset of breast feeding

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Should we treat the child and not the mother ?

• Yes, it is possible to give prophylaxis to the
  child
• But it acts in a different way
• Mother indetectable VL
• Infant post exposure prophylaxis

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SIMBA (Stopping Infection from Mother-to-child
from Breastfeeding in Africa) Prophylaxie chez
lenfantVyankandondera J et al. IAS Meeting,
Paris France 2003
Protection de lenfant par une prophylaxie de 6
mois par 3TC vs NVP avec un allaitement maternel
exclusif
Bras 1
Mère AZT ddI x 1 sem
AZT ddI début 36 s
AZT ddI
Enfant 3TC x 6 mois
Bras 2
AZT ddI
AZT ddI début 36 s
Mère AZT ddI x 1 sem
Enfant NVP x 6 mois
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SIMBAPackage résultats 2 de transmission
Intrapartum/Postnatale . Vyankandondera J et al.
IAS Meeting, Paris, France 2003
Naissance
lt 4 sem.
4 sem. 6mois
Taux de transmission
6
1
1
8
(Pas de différence significative entre les 2 bras
3TC vs NVP)
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Which prophylaxis for the child ?

• Acording to WHO 2006
• Sd-NVP and AZT for one week
• If the mother receives less than four weeks of
  AZT before delivery, the AZT dose for the infant
  should be extended to four weeks
• If prophylaxis to protect breast feeding
• AZT 3TC NVP

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Which treatment if the child is infected ?

• WHO april 2008
• All infants under 12 months of age with confirmed
  HIV infection should be started on antiretroviral
  therapy, irrespective of clinical or
  immunological stage.

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Criteria to start ART(WHO april 2008)
age lt 12 months 12 35 months 36 59 months 5 yo and gt
CD4 Treat all lt 20 lt 20 lt 15
Absolute CD4 Treat all lt 750 lt 350 lt 200
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WHO april 2008

• RECOMMENDATION
• For HIV infected infants with a history of
  exposure to single dose nevirapine or
  non-nucleoside reverse transcriptase inhibitor
  containing maternal antiretroviral therapy or
  preventive antiretroviral regimens, a protease
  inhibitor-based triple antiretroviral therapy
  regimen should be started.
• Where protease inhibitors are not available,
  affordable or feasible, nevirapine-based therapy
  should be used.

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Recommended first line regimen in children

• 2 NRTI 1 IP/r

ABC 3TC
AZT 3TC LPV/r
AZT ABC
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Conclusion 1

• PMTCT with triple therapy lower the risk of MTC
  transmission
• Formula feeding is without risk for HIV
  transmission but
• Alternative feeding option should be proposed as
  triple prophylaxis protected breast feeding for 6
  months

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Conclusion 2

• But for an efficient PMTCT efforts should be
  made on
• Follow up of the children (too many lost for
  follow up)
• Organization of PMTCT in term of
• Human resources
• monitoring (laboratory exam)
• Community support

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Thank You !