PMTCT: a moving target or a moving strategy?

1. PMTCT: a moving target or a moving strategy? 23rd June 2008 MSF Access Campaign

2. Objectives of the meeting • To review recent data with scientific experts, implementers etc. • To balance new evidence with remaining gaps in knowledge • To define where new data needs to be generated and where implementation can start

3. Agenda • Monday • Treatment of the mother • Implementation • Cost-effectiveness data • Tuesday • Treatment of the infant • Summary: role for advocacy? New evidence needed or operational research or implementation/cost obstacles?

4. Context • No controversy on the role of HIVRNA suppression to decrease HIV transmission

5. Tous Homme-Femme Femme-Homme Pas de transmission si CV « indétectable » Etude « Rakai »: Risque de transmission en fonction de la charge virale Quinn et al. N Engl J Med 2000;342:921-9

6. N Engl J Med 1999;341:394-402 Maternal levels of plasma HIV RNA and the risk of perinatal transmission Maternal HIVRNA of a NON infected infant Maternal HIVRNA of an infected infant No transmission if mother’s viremia below 1000 copies

7. Evolution of MTCT rates over time AZT HAART Percent of infected infants We will review randomized trials (AMATA, Kesho Bora) and DREAMS data

8. Effect of cART on MTCT • 2705 infants from HIV infected mothers, whom HIVRNA was undetectable from week 36 to week 40 • 3 infants were infected Claire Townsend et al. 15th CROI, Poster 653

9. Breastfeeding transmission Mothers on NVP/3TC/AZT, 2 studies in Kenya and Uganda. 441 and 172 pregnancies, 1 infection Percent of infected infants IAS Conference Sydney, Abstracts TUAX 101 and 102

10. Antepartum Evaluation of Optimal Antepartum PMTCT Strategy • US/UK guidelines state persons with CD4 <350 should get HAART for own health. • Women with CD4 <350 are at greatest risk of MTCT even with short-course ART and of NVP resistance following SD NVP. • Thus, there is no controversy about what to do for pregnant women with low CD4 - give cART as treatment for own health and continue after birth.

11. Antepartum Evaluation of Optimal Antepartum PMTCT Strategy • However, there is uncertainty about optimal strategy for women with CD4 >350. • Women with CD4 >350 have lower baseline risk of MTCT and lower risk of developing resistance. • Obstacles to universal pregnancy coverage: • Issue of interrupting cART? (what does the experience of wealthy countries teach us?) (B.Hirschel) • Concerns regarding pregnancy outcome and HAART? (Preterm, Europe, low birth rate, IC) • Limited formulary? • Limited resources? Complexity of implementation?

12. Context • No controversy about the importance and the possibility to eradicate MTCT • But HOW? • Is there a failure of current PMTCT strategy? (S. Balkan) • Can changes in ART combinations lead to a change in strategy? (R.Tubiana) • Is coverage of 100% pregnant women regardless of CD4 cell count feasible and desirable? • CD4 below or above 350 cell count: how this should – or should not stratify the strategy? • What is the ongoing research agenda? (F. Dabis and L. Ciaffi)

13. 6-Week MTCT Risk in Women NotMeeting WHO Criteria*for ART Who Receive Short-Course ARV ProphylaxisCote d’IvoireTrials Data, F. Dabis 6/05 Short AZTAZT+AZT/3TC+HAART SD NVPSD NVP * Does not Meet WHO criteria if: WHO Stage 3 and CD4 >350 or Stage 1-2 and CD4 >200

14. Finding the balance • Cons • Effect of cART on children • Treatment interruption (mother) • Cost • Complexity in implementation • Pro • Effectiveness in • preventing the transmission • Lowering long term • cost by preventing • children’s infection • - Preventing resistances?

15. Thanks for participating • We hope that at the end of the meeting, we will have a clear idea on • whether to wait new evidence, • or start with implementation strategy for cART for all pregnant women