1 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.

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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

MSF Geneva June 24th 2008

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 2

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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


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 (< 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 ?

• 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)

CROI 2008 abstract 72 M.Mirochnick et al


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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


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….


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


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

12MSF Geneva June 24th 2008


SIMBA: (Stopping Infection from Mother-to-child from Breastfeeding in

Africa) – Prophylaxie chez l’enfantVyankandondera J et al. IAS Meeting, Paris France 2003

Enfant: NVP x 6 mois

Enfant: 3TC x 6 mois

Mère: AZT + ddI x 1 sem

AZT +ddI début 36 s

AZT +ddI

AZT +ddI début 36 s

Mère: AZT + ddI x 1 sem

AZT +ddI

Bras 1:

Bras 2:

Protection de l’enfant par une prophylaxie de 6 mois par 3TC vs NVP avec un allaitement maternel exclusif


SIMBA“Package” résultats : 2% de transmission Intrapartum/Postnatale .

Vyankandondera J et al. IAS Meeting, Paris, France 2003

Taux de transmission

Naissance < 4 sem. 4 sem. – 6mois

6% 1 % 1 %

8 %

(Pas de différence significative entre les 2 bras : 3TC vs NVP)

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


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.


Criteria to start ART(WHO april 2008)

age < 12 months

12 – 35 months

36 – 59 months

5 yo and >

% CD4 Treat all < 20 < 20 < 15

Absolute CD4

< 750 < 350 < 200


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.



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


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



1 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.

Documents

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