Review of recent changes in WHO and national paediatric care guidelines Dr. Chewe Luo UNICEF New York City, USA

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1 Review of recent changes in WHO and national paediatric care guidelines Dr. Chewe Luo UNICEF New York City, USA

2 Review of recent changes in WHO and national paediatric care guidelines Dr. Chewe Luo MMed (Paediatrics), MTrop Paed, PhD Senior Adviser and Team Leader Country Programme Scale up HIV Section Program Division UNICEF Headquarters New York Interest meeting Lusaka 5 th -13 th May 2014

3 DISCLOSURE DISCLOSURES Research Support/P.I. Employee UNICEF Consultant Major Stockholder Speakers Bureau Honoraria Scientific Advisory Board Presentation includes discussion of the off-label use of a drug or drugs

4 OUTLINE PMTCT progress Progress in child survival in Africa 2013 WHO guidelines Country evolution of the guidelines Optimal IATT list Conclusions 4

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6 Children in need of ART 21 Priority countries MAX Adult ART coverage 95% PMTCT coverage 95% Paediatric ART coverage 100% to 2 3 to 4 5 to 9 10 to 14 Presented by Martina Penazzato at the Paediatric treatment optimization meeting, Dakar 2013

7 HUGE DISPARITIES BETWEEN ADULTS AND CHILDREN PERCENTAGE OF ART COVERAGE AMONG ELIGIBLE ADULTS (AGED 15+), CHILDREN (AGED 0 14) AND ALL AGES 22 GLOBAL PLAN PRIORITY COUNTRIES, % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% >95 >95 Botswana Namibia Swaziland 38 Zambia 45 Zimbabwe South Africa 38 Kenya Malawi 7 33 Uganda Uni. Rep. 24 Ethiopia 21 Burundi Ghana Lesotho India Côte d'ivoire Cameroon Adults (aged 15+) Children (aged 0 14) All ages Note: Some numbers do not add up due to rounding. The coverage estimate is based on the estimated unrounded number of children receiving and eligible for ART. Source: UNAIDS, UNICEF and WHO, 2013 Global AIDS Response Progress Reporting. 27 Mozambique 15 Angola Chad 38 9 DRC Nigeria Total

8 Progress towards achievement of the fourth Millennium Development Goal in the African Region, 2006 to 2012 Source: United Nations Children s Fund, Progress for Children: A World Fit for Children statistical review, Number Double 6, UNICEF, Dividend New York, 2007, Think p. Tank 19. Meeting April 2014, Harare, Zimbabwe Source: UNICEF, WHO, World Bank, UNDESA. Levels and Trends in Child Mortality: Report Estimates Developed by the United Nations Inter-agency Group for Child Mortality Estimation, New York, UNICEF 2011 Source: UNICEF, WHO, World Bank, UNDESA. Levels and Trends in Child Mortality: Report Estimates Developed by the United Nations Inter-agency Group for Child Mortality Estimation, New York, UNICEF 2013

9 WHO 2013 Paediatrics Guidelines ART should be initiated in all children below five years of age, regardless of CD4 count or WHO clinical stage. Infants diagnosed in the first year of life (strong recommendation, moderate-quality evidence). Children infected with HIV between one and below five years of age (conditional recommendation, very low-quality evidence). ART should be initiated in all children five years of age and older with CD4 cell count 500 cells/mm 3, regardless of WHO clinical stage. CD4 count 350 cells/mm 3 (strong recommendation, moderate-quality evidence). CD4 count between 350 and 500 cells/mm 3 (conditional recommendation, very-lowquality evidence). LPV/r-based regimen for children <3 years, regardless of NNRTI exposure with ABC + 3TC or AZT + 3TC EFV-based regimens for children > 3 years For 3 years to < 10 years (or <35 kg), the NRTI backbone ABC + 3TC AZT or TDF + 3TC or FTC For children 10 years and 35 kg, TDF + 3TC or FTC ; AZT + 3TC; ABC + 3TC

10 Overcoming the operational challenges of using LPV/r in country Cold chain programmes Poor palatability impacts on adherence No FDC available Lack of second line options Interaction with TB drugs Sprinkles - 4in1 FDC are under development Simplification by switching to NVP once virological suppression is achieved is safe in children without baseline resistance to NNRTI (Coovadia et al 2010) 3NRTI regimen to be considered as an option for the duration of TB cotreatment (Arrow trial 2013)

11 Recommendations 2013, switching to 2 nd line Failure of a first-line NNRTI-based regimen a boosted PI plus two NRTIs (LPV/r is the preferred boosted PI) (Strong recommendation, moderate-quality evidence) Failure of a first-line LPV/r-based regimen in children < 3 years old Remain on the same regimen plus improve adherence (Conditional recommendation, very-low-quality evidence) Failure of a first-line LPV/r-based regimen in children > 3 years NNRTI plus two NRTIs; EFV is the preferred NNRTI (Conditional recommendation, low-quality evidence) NRTIs backbone substitution after treatment failure ABC or TDF + 3TC (or FTC) AZT + 3TC AZT or d4t + 3TC (or FTC) TDF + FTC or ABC + 3TC

12 National programmes Develop policies for third-line ART (conditional recommendation, low-quality evidence). 2 nd line treatment failure Explore strategies that balance the benefits and risks for children when second-line treatment fails. 3 rd line options available For older children and adolescents who have more therapeutic options available to them, constructing third-line ARV regimens with novel drugs used in treating adults such as ETV, DRV and RAL may be possible. No new drug options available Recommendations 2013, switching to 3 nd line Children on a second-line regimen that is failing with no new ARV drug options should continue with a tolerated regimen. If ART is stopped, opportunistic infections still need to be prevented, symptoms relieved and pain managed. Summary of recommendations of new consolidated 2013 WHO HIV guidelines,

13 Evolution of first line 100,0 90,0 APIs evolution for children 1 st line, ,0 % of treated patients 70,0 60,0 50,0 40,0 30,0 20,0 10,0 d4t AZT ABC LPV 0, Courtesy Vincent Habiyambere, WHO 2013 Year

14 Evolution of second line % of treated patients Evolution of the main children second line regimens, Year Courtesy Vincent Habiyambere, WHO 2013 ABC+3TC+LPV/r AZT+ddI+LPV/r ABC+ddI+LPV/R AZT+3TC+LPV/r AZT+ddI+EFV d4t+3tc+lpv/r TDF+3TC+LPV/r AZT+ABC+3TC+LPV/r d4t+3tc+abc

15 10 Formulations on IATT Optimal List, 2014 Drug Class Drug Formulation Dose NRTI AZT Oral liquid 50mg/5mL NNRTI EFV Tablet (scored) 200mg NNRTI NVP Tablet (disp, scored) 50mg NNRTI NVP Oral liquid 50mg/5mL PI LPV/r Tablet (heat-stable) 100mg/25mg PI LPV/r Oral liquid 80mg/20mg/mL FDC AZT/3TC Tablet (disp, scored) 60mg/30mg FDC AZT/3TC/NVP Tablet (disp, scored) 60mg/30mg/50mg FDC ABC/3TC Tablet (disp, scored) 60mg/30mg FDC ABC/AZT/3TC Tablet (non disp, scored) 60mg/60mg/30mg 15

16 CONCLUSIONS We are making progress although there are many programmatic challenges New guidelines have opened an opportunity for prioritizing products to simplify treatment

17 ACKNOWLEDGEMENTS Vincent Habiyambere - WHO Martina Penazzato - WHO Raul Gonzales Montero - WHO Teshome Desta Woldehanna - WHO Jessica Rodrigues - IATT 17