Treatment of Children and AdolescentsImplementation Challenges

Annette H. Sohn, MDTREAT Asia/amfAR – ThailandAIDS 2014

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

Pediatric Treatment and CoverageStill [much] slower than adults

2009 2010 2011 2012 20130

100,000

200,000

300,000

400,000

500,000

600,000

700,000

800,000

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Peds ART# Peds coverage% Adult coverage%

Sources: UNAIDS/UNICEF/WHO reports 2010-2013; aidsinfoonline.org; WHO Global Update on the Health Sector Response to HIV 2014.

IeDEA Southern AfricaEarlier treatment over time

N=30,300

Davies MA, PLoS One. 2013 Dec 9;8(12):e81037.

The Future of New InfectionsSicker 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

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 4Children >5 years: All a) <500 cells/mm3, b) WHO stage 3 or 4

Conditional: 1-5 years, CD4 350-500 in >5 years

HIV-exposed infants receiving a virological test by 2 months of age, 2010–2012

UNICEF, Children and AIDS, 6th Stocktaking Report, 2013.WHO Global Update on the Health Sector Response to HIV 2014.

Treat all <2 years

2013

What about the pediatric cascade?

Total On ART Viral suppression0

500,000

1,000,000

1,500,000

2,000,000

2,500,000

3,000,000

3,500,000

Children <15 years, 2013

23%

???

WHO Global Update on the Health Sector Response to HIV 2014.

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+NVP3-10 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.

Planning for the Future

• Dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF) for 1st-line– DTG: US FDA >12 yrs, Aug 2013

• IMPAACT P1093, Phase I/II: 6-12 yrs; South Africa, Thailand1

– TAF • Gilead, Phase II/III: 12-<18 yrs; South Africa, Thailand, Uganda2

• Boosted darunavir (DRV/r) for 2nd-line– US FDA >3 yrs + >10 kg; liquid, peds tablets– Cost per year, adults: Thailand $3000,3 India $1632,4

least-developed countries $800-10005

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.

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 data1

• Outcomes: Mixed – Asia, perinatal: 71% CD4 >500, 87% viral suppression2

– Zimbabwe-MSF: mortality similar to adults, higher 2nd-line3

– Global: 2nd leading cause of adolescent death; 1st in Africa4

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 Report2. 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.

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 – ThailandTulloch O, PLoS One. 2014 Jun 3;9(6):e99061.

*WHO, HIV and Adolescents, 2013.

Trying to Close the Gaps

• UNICEF/WHO/EGPAF: The Double Dividend1

– 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 behind2

– Engaging youth advocates and PLHIV networks to demand optimal care and treatment1. http://www.unicef.org/aids/files/Action_Framework_Final.pdf

2. http://www.gnpplus.net/assets/2014_NoALHIVLeftBehind4-copy.pdf

The Future of Pediatric HIV?

Eligible for ART On ART 90-90-90 ART target

0

500,000

1,000,000

1,500,000

2,000,000

2,500,000

3,000,000

3,500,000

2013 2020

WHO Global Update on the Health Sector Response to HIV 2014. WHO, March 2014 supplement to the 2013 consolidated guidelines.

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