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Pr C. Courpotin

Pr C. Courpotin

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Pr C. Courpotin

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  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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 MSF Geneva June 24th 2008

  8. 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 HIVsuppession and development of drug resistance) MSF Geneva June 24th 2008

  9. 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

  10. 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

  11. 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

  12. 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 MSF Geneva June 24th 2008

  13. SIMBA: (Stopping Infection from Mother-to-child from Breastfeeding in Africa) – Prophylaxie chez l’enfantVyankandondera 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 Bras 2: AZT +ddI début 36 s AZT +ddI Mère: AZT + ddI x 1 sem Enfant: NVP x 6 mois MSF Geneva June 24th 2008

  14. SIMBA“Package” résultats : 2% de transmission Intrapartum/Postnatale .Vyankandondera J et al. IAS Meeting, Paris, France 2003 Naissance < 4 sem. 4 sem. – 6mois Taux de transmission 6% 1 % 1 % 8 % (Pas de différence significative entre les 2 bras : 3TC vs NVP) MSF Geneva June 24th 2008

  15. Which prophylaxis for the child ? • Acording to WHO 2006 : • Sd-NVPand 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

  16. 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

  17. Criteria to start ART(WHO april 2008) MSF Geneva June 24th 2008

  18. 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. MSF Geneva June 24th 2008

  19. Recommended first line regimen in children 2 NRTI + 1 IP/r MSF Geneva June 24th 2008

  20. 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

  21. 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

  22. Thank You ! MSF Geneva June 24th 2008