Transcript Advantages and risks for a child to be exposed to the

Advantages and risks for a child
to be exposed to the triple
prophylaxis during pregnancy
and breastfeeding
What is the best for the child ?
Pr C. Courpotin
MSF Geneva June 24th 2008
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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)
MSF Geneva June 24th 2008
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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
MSF Geneva June 24th 2008
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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 ?
MSF Geneva June 24th 2008
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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
MSF Geneva June 24th 2008
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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)
MSF Geneva June 24th 2008
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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 (< 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 ( > plasma)
– NVP : concentrates in BM ( > 3400 ng/ml therapeutic
drug monitoring program in some children (risk of
potential drug toxicity, partial HIV suppession and
development of drug resistance)
MSF Geneva June 24th 2008
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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
MSF Geneva June 24th 2008
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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….
MSF Geneva June 24th 2008
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Triple prophylaxis and late coming of
the mother or incomplete protocols
• Mother’s VL should be undetectable at the
time of the onset of breast feeding
MSF Geneva June 24th 2008
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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 l’enfant
Vyankandondera J et al. IAS Meeting, Paris France 2003
Protection de l’enfant par une prophylaxie de 6 mois par
3TC vs NVP avec un allaitement maternel exclusif
Bras 1:
AZT +ddI début
36 s
AZT
+ddI
Mère: AZT
+ ddI x 1 sem
Enfant: 3TC x 6 mois
AZT
+ddI
Mère: AZT
+ ddI x 1 sem
Enfant: NVP x 6 mois
Bras 2:
AZT +ddI
début 36 s
MSF Geneva June 24th 2008
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SIMBA“Package” résultats : 2% de
transmission Intrapartum/Postnatale .
Vyankandondera J et al. IAS Meeting, Paris, France 2003
Naissance
Taux de
transmission
6%
< 4 sem.
1%
4 sem. – 6mois
1%
8%
(Pas de différence significative entre les 2 bras : 3TC vs NVP)
MSF Geneva June 24th 2008
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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
MSF Geneva June 24th 2008
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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.
MSF Geneva June 24th 2008
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Criteria to start ART
(WHO april 2008)
age
% CD4
Absolute
CD4
< 12
months
Treat all
12 – 35
months
< 20
36 – 59
months
< 20
5 yo and >
< 750
< 350
< 200
MSF Geneva June 24th 2008
< 15
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WHO april 2008
• RECOMMENDATION:
– For HIV infected infants with a history of
exposure to single dose nevirapine or nonnucleoside 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.
MSF Geneva June 24th 2008
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Recommended first line regimen in
children
2 NRTI + 1 IP/r
ABC + 3TC
AZT + 3TC
AZT + ABC
MSF Geneva June 24th 2008
LPV/r
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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
MSF Geneva June 24th 2008
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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
MSF Geneva June 24th 2008
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MSF Geneva June 24th 2008
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