Aspirations, Innovations and a Touch of Reality - Reaching for Children. Elaine J Abrams Columbia University June 18, 2014

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Aspirations, Innovations and a Touch of Reality - Reaching 90.90.90 for Children Elaine J Abrams Columbia University June 18, 2014

Reaching 90.90.90 Define 90.90.90 Global update on pediatric care and treatment Testing, Treatment & Viral Suppression Where we are now Opportunities & innovations Barriers to progress General reflections and considerations

A new narrative on HIV treatment and a new final, ambitious, but achievable target, UNAIDS, Oct 2014 By 2020, 90% of all people living with HIV will know their status By 2020, 90% of all people with diagnosed HIV infection will receive sustained antiretroviral treatment By 2020, 90% of all people receiving antiretroviral treatment will have viral suppression By 2020, 73% of all individuals living with HIV globally should be virally suppressed

New and current HIV infections among children, 0-14 years, globally 700 000 7 000 000 600 000 6 000 000 500 000 5 000 000 400 000 4 000 000 300 000 3 000 000 200 000 2 000 000 100 000 1 000 000 Estimated number of children (0-14) living with HIV Number of children (0-14) newly infected with HIV http://www.unaids.org/en/resources/campaigns/2014/2014gapreport/gapreport/ http://www.unaids.org/en/resources/campaigns/howaidschangedeverything/factsheet

HIV infection among adolescents, 10-19 years of age Globally, it is estimated that there are approximately 2.1 million adolescents living with HIV Includes perinatal and behavioral acquisition 750,000-900,000 adolescents ages 10-14 years 58% of adolescents with HIV are female There were an estimated 250,000 new HIV infections among 15-19 year olds in 2013 2/3 of all new adolescent infections occurred among girls UNICEF, Taking Stock Report, 2013; All In: Global Strategy Report, UNAIDS, 2014

http://allintoendadolescentaids.org Number of adolescents by mode of infection, 25 countries

Pediatric 90-90-90 2.6 million children, 0-14 years of age 2.3 million diagnosed HIV+ 2.1 million receiving ART 1.9 million virally suppressed

Infants, children and adolescents 90-90-90 3.7 million diagnosed HIV+ 3.3 million receiving ART 3.0 million virally suppressed

By 2020, 90% of all children living with HIV will have known HIV status HIV TESTING

Proportion of HIV exposed infants with EID testing Improving but inadequate uptake of EID: 42% of exposed infants tested in 2013

Entry into care and diagnostic testing in HIVexposed infants, Malawi, June 2014-June 2015 16000 14000 12000 10000 8000 6000 4000 2000 Only 60% enrolled into care Ideal 12 mo cohort Only 40% of those enrolled were tested 0 HIV exposed infants Enrolled in HIV care Received diagnostic HIV test Charts constructed using data from the Malawi Ministry of Health Q2 (April-June 2015) report

90-90-90 for children 18mo-14yr Kenya AIDS Indicator Survey (KAIS) 80% 70% 60% 50% 40% 30% 20% 10% 39% 73% 50% 3681 children tested 28 (0.9% 95% CI:0.5-1.3) tested HIV positive 11(39%) previously diagnosed 8 (73%)on ART 4 (50%) virologically suppressed 0% Known HIV+ status Receiving ART Virologically suppressed Ng eno et al, JAIDS, 2014

Number of adolescents, 10-19 years, who know their status, Tanzania http://allintoendadolescentaids.org

Strategies for identifying HIV-infected infants, children, and adolescents Reaching 90-90-90 http://www.pepfar.gov/documents/organization/244347.pdf

Strengthening the EID care cascade HIV positive pregnant woman on ART Infant enrolled in PMTCT follow-up EID sample obtained at 6 weeks of age Sample transported to laboratory Sample tested for HIV at laboratory EID results returned to the clinic EID results returned to the family Retained in care; repeat testing at end of exposure period Immediate ART initiation

Innovations to strengthen the Early Infant Diagnosis (EID) and care cascade Birth Testing Point of Care (POC) Diagnostic Testing Centralized transport schemes SMS printers SMS reminders Appointment systems with active follow-up Community health workers

HIV Infant Tracking System improves EID quality and retention, Kenya Innovative on-line system, algorithm-based computer alerts for staff and text messaging alerts to mothers Finocchario-Kessler et al, AIDS 2014

Facility and home based testing by Community Health Workers, Malawi Ahmed S et al, JIAS, 2015

Routine PITC in primary health care clinics to identify adolescents with HIV, Zimbabwe 6 primary care clinics, ages 6-15 years, 2013 Kranzer K et al PLOS Medicine 2014 2 primary care clinics, ages 10-18 years, 2009 Ferrand R et al, CID 2010

Obstacles along the road to 90-90-90 Defining and obtaining CONSENT to test infants, children and adolescents Health worker shortages, capacity, roles and responsibilities Supply chain challenges

By 2020, 90% of all people with diagnosed HIV infection will receive sustained antiretroviral treatment By 2020, 90% of those with diagnosed HIV infection will receive sustained antiretroviral treatment ANTIRETROVIRAL TREATMENT

An estimated 832,000 children, 0-14 years, received ART in 2014 41% 32% Estimated proportion of eligible adults and children receiving ART by year 2014 UNAIDS 2014 HIV and AIDS Estimates, July 2015

Antiretroviral coverage in children by region, 2000-2014, UNAIDS estimates

ART initiation among HIV-infected infants, Malawi, June 2014-June 2015 800 700 600 500 400 300 200 100 0 ART eligible ART initiated Ideal 12 mo cohort Majority of infected infants not being identified or started on ART Charts constructed using data from the Malawi Ministry of Health Q2 (April-June 2015) report

Early infant diagnosis ART initiation Francistown, Botswana, 2005-2012 N=153 N=123 N=82 Motwere-Chiwra, MMWR, 2014

Improvements over time but most children initiate ART at advanced disease stage Davies MA et al, PLOS One 2013

Access to CD4 still limited, particularly at the primary care level, Lablite Project 100% Regular access to CD4 testing among facilities providing ART 80% 60% 40% 20% Referral On-site 0% Malawi Uganda Zimbabwe Chan AK et al BMC Health Services Research 2014

High rates of attrition (death and loss to follow-up) among children on ART 67% retention at 36 months Fox & Rosen, AIDS 2015

Strategies for increasing the number of infants, children & adolescents initiating ART Reaching 90-90-90 Universal treatment for all infants, children, and adolescents Expand ART access Decentralization, nurse managed ART, community-based ART Newborn HIV Testing Earlier identification and engagement of HIV-infected infants, POC diagnostics

Improved ART access and uptake among pregnant and breastfeeding women, Malawi Increase in number of ART sites Option B+ starts Transition from prophylactic ARV regimens for PMTCT to Option B+ in Malawi 8 fold increase in maternal ART initiations Option B+ starts Schouten, Presentation at SADC Meeting, 2012 Government of Malawi, Ministry of Health, Integrated HIV Program Report, Jul-Sep 2013

New ART initiations among pregnant and breastfeeding women, percentage of all new ART initiations attributed to this population, Malawi 2008-2012 (CDC, MMWR 2013) Substantial increase in ART initiations for pregnant & breastfeeding women, Malawi In1 st year of B+ implementation, the number of pregnant and breastfeeding women initiating ART increased 748% (CDC, MMWR 2013)

Increase in ART uptake with Option B+ in 7 countries, EGPAF, 2011-2013 Keiffer MP, JAIDS, 2014

Option B+ simplifies delivery of PMTCT Maternal therapeutic ART (TDF + 3TC/FT + EFV) Reduced steps in the cascade No need for CD4 or clinical staging to initiate ART Harmonizes regimens for the PMTCT and ART programs Easily implemented by nurses and non-specialist physicians

No. of Children 0-14 Yrs Children, 0-14 years, newly enrolled in HIV and newly initiating ART, ICAP Kenya 900 800 700 ART for ALL children <10yrs 600 500 400 300 Males new in Care Females new in care Males initiating ART Females initiating ART 200 100 Oct-Dec 2013 Jan-Mar 2014 Apr-Jun 2014 Jul-Sep 2014 Oct-Dec 2014 Jan-Mar 2015

Expand access to ART for children Decentralization to primary care facilities Enhance health worker capacity to treat infants, children and adolescents at lower level facilities Ensure integrity of the ARV supply chain Innovations in service delivery: family-focused care, community, school and home based ART Fayorsey R, JAIDS 2014

Newborn testing may lead to more infants starting treatment early Lilian R et al PIDJ 2013

Obstacles along the road to 90-90-90 Pressing need to engage with the behavioral and psychosocial issues affecting children and families affected by HIV particularly disclosure and sexual and reproductive health Better drugs and drug formulations for pediatric populations Address health worker shortages, capacity, roles and responsibilities Supply chain challenges

Initiation is only the first step in a lifetime of antiretroviral treatment

By 2020, 90% of those receiving antiretroviral treatment will have viral suppression VIRAL SUPPRESSION

Viral suppression in the pediatric population Rates of viral suppression vary by population, age, gender, drug regimen, calendar year, duration of treatment, lower limit of detection, study design, frequency of measurement Published rates of viral suppression with first-line ART generally range from ~ 60% to 90% Cross-sectional analysis of adults and children on ART in Swaziland: <10yr (n=588) 71% suppression; 10-19yr (n=580) 65% VS; 20+yr (n=10,808) 86% Among 4803 children on ART in South Africa, in crude analyses, at any time-point on treatment, suppression was 65.6% (95%CI 62.7-68.4%) in community based adherence support (CBAS) children; 55.5% (95%CI 54.1-57%) in non- CBAS children Jobanputra K et al PLOS ONE 2015 Fatti G et al AIDS Care 2013

Viral suppression on ART among children participating in the ARROW study ARROW Trial Team, Lancet 2013

Proportion of adolescents Rates of viral suppression among 649 perinatally infected youth, US 90 80 70 60 50 40 30 20 10 0 0-5yr (n=93) 8-10yr >11yr (n=107) (n=335) Time since diagnosed with HIV on ART viral suppression Column1 on ART >6m adherence >90% viral suppression Kahana, JAIDS, 2015

Strategies for achieving viral suppression among infants, children & adolescents Reaching 90-90-90 Better drugs: more potent, robust, durable, safe, long acting, fixed dose combination regimens Integrase inhibitors, long acting formulations (LAF) Innovative models of care and approaches to adherence support Addressing the developmental complexities across the trajectory from infancy through adulthood, for individuals, within families and communities

Risk of psychotic exacerbation/relapse lower for long-acting injectable vs oral risperidone JAMA Psychiatry. Published online June 24, 2015. doi:10.1001/jamapsychiatry.2015.0270

Dual therapy with cabotegravir long acting and rilpiverine long acting injectable, LATTE and LATTE-2

Zvandiri community care and support model, Zimbabwe

Bolster key family and youth processes VUKA & CHAMP+ASIA

Obstacles along the road to 90-90-90 Prolonged duration for drug development Adherence to chronic, daily medication regimens is poor across multiple disease Pressing need to engage with the behavioral and psychosocial issues affecting children and families affected by HIV particularly disclosure and sexual and reproductive health

Aspirations, Innovations and a Touch of Reality - Reaching 90.90.90 for Children Targets are good but justifiably aspirational Relatively good experience with 3x5, MDGs Opportunity to direct attention to pediatric populations, somewhat neglected Achieving 90.90.90 will require focused attention, political will, innovation, and more than a bit of luck Into the future, however, the best hope for children will be to PREVENT new infections another target (elimination) we now have the tools to achieve

Cuba ends mother-to-child transmission of HIV and syphilis

THANKS EVERYONE!