1. Treatment of Children and Adolescents Implementation Challenges Annette H. Sohn, MD TREAT Asia/amfAR – Thailand AIDS 2014

2. Outline The status of pediatric treatment Implementing the WHO 2013 ART guidelines –When to start –What to start with –Adolescents Global policy efforts to close the gaps

3. Pediatric Treatment and Coverage Still [much] slower than adults Sources: UNAIDS/UNICEF/WHO reports 2010-2013; aidsinfoonline.org; WHO Global Update on the Health Sector Response to HIV 2014.

4. IeDEA Southern Africa Earlier treatment over time N=30,300 Davies MA, PLoS One. 2013 Dec 9;8(12):e81037.

5. The Future of New Infections Sicker infants with resistant virus Increasing success of PMTCT programs –Infected infants with higher risk of in utero transmission, ARV exposures  resistance NNRTI resistance in a South African cohort* –PMTCT ARVs: 57% at median 19 weeks of age –“No” ARVs: 24% at median 42 weeks of age Graphic: Abrams E, CROI 2010 plenary. *Kuhn L, AIDS. 2014 Apr 30. Data from 2011: N=230 under 2 years at diagnosis. PMTCT scale-up NNRTI resistance No NNRTI resistance

6. When to Start Why –Treat all <5 to simplify and expand ART access, <500 to align with adults Challenges –Early infant diagnosis –Finding older children in the community Infants/toddlers: All a) <5 years, b) WHO stage 3 or 4 Children >5 years: All a) <500 cells/mm3, b) WHO stage 3 or 4 Conditional: 1-5 years, CD4 350-500 in >5 years

7. HIV-exposed infants receiving a virological test by 2 months of age, 2010–2012 UNICEF, Children and AIDS, 6 th Stocktaking Report, 2013. WHO Global Update on the Health Sector Response to HIV 2014. Treat all <2 years 2013

8. What about the pediatric cascade? 23% ??? WHO Global Update on the Health Sector Response to HIV 2014.

9. What to Start With Why –LPV/r to avoid resistance; EFV for better viral suppression; ABC to avoid TAMs Challenges –LPV/r liquid: storage, taste, impact on growth –ABC: drug access, lower viral suppression vs. d4T in Southern Africa (54% vs. 70%)* First-line ART, <3 years: ABC/AZT+3TC+LPV/r Alternate: ABC/AZT+3TC+NVP 3-10 years: ABC+3TC+EFV Alternate: AZT+3TC+EFV, ABC/AZT+3TC+NVP, TDF+3TC/FTC+EFV/NVP *Technau KG, Pediatr Infect Dis J. 2014 Jun;33(6):617-22.

10. Planning for the Future Dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF) for 1 st -line –DTG: US FDA >12 yrs, Aug 2013 IMPAACT P1093, Phase I/II: 6-12 yrs; South Africa, Thailand 1 –TAF Gilead, Phase II/III: 12-<18 yrs; South Africa, Thailand, Uganda 2 Boosted darunavir (DRV/r) for 2 nd -line –US FDA >3 yrs + >10 kg; liquid, peds tablets –Cost per year, adults: Thailand $3000, 3 India $1632, 4 least-developed countries $800-1000 5 WHO, March 2014 supplement to the 2013 consolidated guidelines. 1. Viani RM, CROI 2013, #901. 2. NCT01854775. 3. Anonymous Clinic, Thai Red Cross 4. DNP+, New Dehli. 5. Untangling the web, MSF, 2013.

11. Adolescents 10-19 yrs: Same as adults? –Perinatal vs. behavioral infection –Lack of youth-targeted approaches in adult clinical settings Coverage: Only 30 of 193 UN countries reporting data 1 Outcomes: Mixed –Asia, perinatal: 71% CD4 >500, 87% viral suppression 2 –Zimbabwe-MSF: mortality similar to adults, higher 2 nd -line 3 –Global: 2 nd leading cause of adolescent death; 1 st in Africa 4 All <500 cells/mm3 Any CD4 if a) active TB, b) hep B + liver disease, c) serodiscordant partner TDF+3TC/FTC+EFV Alternates: ABC/AZT/TDF+3TC/FTC+EFV/NVP 1. UNAIDS, No adolescent living with HIV left behind, May 2014. Global AIDS Response Progress Report 2. Chokephaibulkit K, Pediatr Infect Dis J. 2014 Mar;33(3):291-4. 3. Shroufi A, AIDS. 2013 Jul 31;27(12):1971-8. 4. WHO, Health for the world’s adolescents, May 2014.

12. Long-term Retention in Care Perinatally infected –Adherence, resistance, disclosure –Transitioning to adult care Behaviorally infected –Less likely to be tested or access and stay in care* –Adolescent key populations at particularly high risk of worse clinical outcomes “All teenagers have some degree of problems, but these ones also have HIV, and so their problems are intensified.” Provider “We hear frequently from organizations who are working with HIV-positive kids that then become adolescents, [they say] that they can't do anything for them anymore” Policy actor Qualitative study – Thailand Tulloch O, PLoS One. 2014 Jun 3;9(6):e99061. *WHO, HIV and Adolescents, 2013.

13. Trying to Close the Gaps UNICEF/WHO/EGPAF: The Double Dividend 1 –Aligning HIV and maternal-newborn-child health strategies, sharing program platforms UNAIDS: 90-90-90 –Setting global targets to identify infected children and get them linked to care/ART UNAIDS/WHO: No adolescent left behind 2 –Engaging youth advocates and PLHIV networks to demand optimal care and treatment 1. http://www.unicef.org/aids/files/Action_Framework_Final.pdf 2. http://www.gnpplus.net/assets/2014_NoALHIVLeftBehind4-copy.pdf

14. The Future of Pediatric HIV? WHO Global Update on the Health Sector Response to HIV 2014. WHO, March 2014 supplement to the 2013 consolidated guidelines.

15. Conclusions The “pediatric” population is changing, requiring new data and models of care –Uptake of new guidelines, aging population –Urgent need for early infant diagnosis and better ways to link and retain adolescents Training and support for providers, health systems Renewed policy efforts to close treatment gaps in the face of funding constraints