S exual and reproductive health, priorities, research and funding

1. Sexual and reproductive health,priorities, research and funding Dr Marleen Temmerman June 2013 Director, Department of Reproductive Health and Research

2. WHO HQ Geneva

3. WHO Departments Family, Women’s and Children’s Health (FWC) Innovation, Information, Evidence and Research (IER) HIV/AIDS, TB, Malaria and Tropical neglected diseases (HTM) Health Security and Environment (HSE) Health Systems and Services (HSS) Non-communicatable diseases and mental health (NMH) Polio, Emergencies and Country Collaboration (PEC)

4. FWC Structure FWC Departments: • Ageing and Life Course (ALC) • Immunization, Vaccines and Biologicals (IVB) • Maternal, newborn, child and adolescent health (MCA) • Reproductive Health and Research (RHR) -> Special Program of Research, Development and Research Training in Human Reproduction (HRP)

6. Mandate HRP Research Standards, norms and guidelines Support to countries Research capacity building

7. Functions of the Department • Providing leadership on matters critical to health and engaging in partnerships where joint action is needed • Shaping the research agenda and stimulating the generation, translation and dissemination of valuable knowledge • Setting norms and standards, and promoting and monitoring their implementation • Articulating ethical and evidence-based policy options • Providing technical support, catalysing change, and building sustainable institutional capacity • Monitoring the health situation and assessing health trends

8. Research • Biomedical • Clinical • Epidemiological • Implementation research • Policy research • Health systems research • Communities research • Social sciences research • Demographic

9. Who’s research? Ownership, demand, sponsors, dissemination • Researcher, individual or group… • On demand: community, public sector, private sector • Involvement of the ‘ demanding’ party is important as well as target group • Who drives the research agenda, who pays and who is accountable? • Registration of all research • Ethical and review boards, DSMB Kesho Bora Interim Results Jul10/Slide 9

10. Who’s research? Ownership, demand, sponsors, dissemination • All parties concerned and needed for high quality research should be involved • Respect for participants and for authorships • Scientific boards per project • Dissemination and communication • Results have to be published • Feedback to the society Kesho Bora Interim Results Jul10/Slide 10

11. "Because of the good credibility of the Programme and WHO in general, HRP's research results have a greater influence on reproductive health policies and standards than the research of any other organization." • (External Evaluation of HRP, • Final Report, 2008)

12. Research capacity strengthening and translation of research into policy and programmes Strengthening the research capacity of investigators and infrastructure in developing countries Supporting researchers to conduct studies based on national priorities in SRH and facilitating their participation in regional and global research Promoting dissemination and utilization of research results and evidence-based guidelines in SRH programmes and services Developing strategies to plan, implement, monitor and evaluate programmes based on research evidence

13. 27 hospitals in Brazil • One year, 85000 women • Piloting the WHO approach and validation of the near-miss criteria 05_XXX_MM13

14. The WHO Multicountry Survey 29 countries, 370 hospitals, 300,000 women, Dec 2011

15. Leading response to world concern on hormonal contraception/HIV risk

16. Odon Device • New, simple, low cost instrument for assisted vaginal delivery • Winner of Saving Lives at Birth Award 2011 • Phase 1 trial ongoing (30 cases so far) • Business plan developed in partnership with a Fortune 500 company

17. Impact of Triple-ARV Prophylaxis during Pregnancy and Breastfeeding Compared with Short-ARV Prophylaxis for MTCT Prevention and Maternal Disease progression Kesho Bora Study Group (Trial registration number ISRCTN71468401) Kesho Bora Interim Results Jul10/Slide 17

18. Background • Majority of MTCT-prevention research focused on saving infant from HIV infection • Care needs of mother (and family) have received relatively little attention • Rapidly increasing access to care in resource-limited settings allows more comprehensive approach to MTCT prevention • Programmes linking MTCT prevention and care beginning to be implemented

19. Rationale • Efficacy of interventions to prevent mother-to-child transmission (MTCT) of HIV in resource-constrained settings must be improved • Health of HIV-infected mothers identified in MTCT-prevention programmes needs more attention • Alternatives to replacement feeding for children born to HIV-infected mothers need to be identified

20. Overall Objective To optimize use of antiretrovirals to reduce risk of MTCT and provide for mother’s health • Explicit link between MTCT-prevention and care • Address key policy questions in providing ARV therapy based on MTCT-prevention intervention

21. Specific objectives Compare efficacy and safety of triple-ARV and short-ARV MTCT-prophylaxis with regard to: • Efficacy: HIV-transmission and infant mortality • Safety: Incidence of severe adverse events in mothers and children • Safety: AIDS-free survival of mothers at 18 months following delivery Kesho Bora Interim Results Jul10/Slide 21

22. Key Justice Considerations • Women who require treatment for their own HIV disease initiate life-long triple ARV therapy • Women not (yet) requiring care receive MTCT-prevention prophylaxis (short-course or extended regimen) • All women whose health deteriorates during study initiate life-long triple-ARV therapy

23. Ethical Challenges • Sustainability • Study period up to 2 years following delivery • Care needs during study provided from study resources • Study being conducted in sites where • Care programme currently exists, or • Care programme under development and expected to be operational before end of study • Close partnerships being developed with governments and NGOs to provide long-term care • Study team not able to provide cast-iron guarantee of long-term care

24. Ethical Challenges • Justice considerations • Priority for initiating triple ARV therapy • Mothers in study who require therapy • Mothers in study whose health deteriorates during study • Mothers in study whose health deteriorates after the study • Under discussion (balance justice vs. resources) • Partners of study volunteers who require therapy • Children of study volunteers who require therapy • Health-care workers involved with study • Community advisory panel to advise (decide?) on who qualifies for long-term care

25. Ethical Challenges • Coercion • Life-long ARV therapy only offered to women volunteering for study cohort • Compliance • Therapy programmes usually require demonstrated ability to comply with burdensome tablet schedule • Violence • Will priority access to ARV therapy for partners expose women to unwanted pregnancy? • Does volunteering for study confer right to free life-long care?

26. Study Outline – Intervention Mother • Amendment introduced during the course of study Kesho Bora Interim Results Jul10/Slide 26

27. Study sites • Bobo Dioulasso, Burkina Faso:Centre Muraz – Nicolas Meda • Mombasa, Kenya:International Centre for Reproductive Health – Stanley Luchters/Marcel Reyners • Nairobi, Kenya:University of Nairobi – Ruth Nduati • KwaDabeka, South Africa:University of KwaZulu-Natal – Nigel Rollins/Kevi Naidu • Somkhele, South Africa:Africa Centre (AFC) – Marie-Louise Newell Nairobi Bobo Dioulasso Mombasa Somkhele KwaDabeka Kesho Bora Interim Results Jul10/Slide 27

28. Screened for RCTn=882 Enrolled in errorn=10 Delivered before allocationn=17 200 ≤ CD4 ≤ 500 and HIV stage < 4n=855 Not randomized, allocatedshort course N=31 Triple ARVn=412 Shortn=412 Flowchart – Randomized Controlled Trial Kesho Bora Interim Results Jul10/Slide 28

29. All infants:HIV infections Log rank test p = 0.029(stratified on centre and intention to BF) No major safety concerns up to 12 months post-delivery Kesho Bora Interim Results Jul10/Slide 29

30. IAS Conference, Cape-Town (July 2009) Revised WHO recommendations (November 2009) Use of ARVs for treating pregnant women and preventing HIV infection in infants Infant feeding in the context of HIV "For the first time, WHO recommends that HIV-positive mothers or their infants take ARVs while breastfeeding to prevent HIV transmission" Kesho Bora Interim Results Jul10/Slide 30

31. Rates of Progression to Stage 3 or CD4<350Women with CD4>=350 at entry Rate of progression from delivery 6 months 12 months 18 months P=0.002 Rate of progression from stopping ARV-prophylaxis 6 months 12 months 18 months P=0.013 Kesho Bora Interim Results Jul10/Slide 31

32. RISKS • Safety OK • Disease progression OK • Resistance ? • BENEFITS • MTCT risk +++ ? +++ Conclusions • Balance of Benefits and Risks of Triple-ARV Prophylaxis: • High rate of progression to CD4<200 (both arms) if CD4 at entry <350 • Reinforces WHO recommendations to treat from 350 • High rate of progression to CD4<350 (both arms) if CD4 at entry >350 • Stresses importance of early initiation of therapy in pregnant women, or women desiring pregnancy Kesho Bora Interim Results Jul10/Slide 32

33. UNIVERSITY OF NAIROBI COLLEGE OF HEALTH SCIENCES SCHOOL OF MEDICINE Participating Institutions Financial Support Kesho Bora Interim Results Jul10/Slide 33

34. Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial The Lancet, Jan 2011 Triple antiretroviral prophylaxis during pregnancy and breastfeeding is safe and reduces the risk of HIV transmission to infants. Revised WHO guidelines now recommend antiretroviral prophylaxis (either to the mother or to the baby) during breastfeeding if the mother is not already receiving antiretroviral treatment for her own health. Kesho Bora Interim Results Jul10/Slide 34

36. HRP research contributes to revised WHO recommendations, high-impact journal manuscript and policy brief on PMTCT • Messages • 43% reduction vs control regimen • breastfeeding continued • mothers own health taken into account • Contributed to evidence for WHO to recommend ARVs while breastfeeding

37. Broadening global reach of evidence-based interventions In 2011 HRP/RHR produced: • 8 policy briefs summarizingkey research findings, policy implications and recommendations • 42 technical publications (in English) • 14 translated into other languages • 135 peer-reviewed research publications Materials produced by RHR/HRP were actively disseminated at over 30 major global conferences or regional meetings

38. Conclusions • Quality of research should be assured through well established mechanisms and procedures • Important to define owner/initiator/benificiary of the research • All research initiatives should be recorded to avoid reporting bias • Conflict of interest to be avoided • Ethical and scientific review mechanisms • Dissemination and publication • Accountability of research and research institutes Kesho Bora Interim Results Jul10/Slide 38