Selected NIH-sponsored HIV Research Studies Involving Women, Adolescents, and

Children

Bill G. Kapogiannis, MD, FAAP

Pediatric, Adolescent & Maternal AIDS (PAMA) Branch

Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH

Bethesda, MD

Disclosures of Financial Relationships

This speaker has no significant financial relationships with commercial entities to

disclose.

This speaker will not discuss off-label use or investigational product during the

program.

This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation.

Learning Objectives

• Recognize past and ongoing studies of the Adolescent Trials Network (ATN)

• Identify past and ongoing studies of the Infant, Maternal, Pediatric, and Adolescent AIDS Clinical Trials group (IMPAACT)

• Discuss future research directions

Choose the correct answer about optimal timing of HAART initiation in HIV+ infants:

A. Initiation at 6-12 weeks of age results in a 3/4 reduction in early infant mortality

B. Deferral of therapy until infant CD4% < 20% does not impact neurodevelopmental outcomes

C. Among infants receiving early HAART, duration of therapy (1 vs 2 years) prior to interruption had little impact on how soon therapy had to be restarted

D. Significantly more infants in whom therapy was deferred required switch to 2nd-line ART on study than those initiating early

A. B. C. D.

0% 0%0%

100%

CHER SchemaHIV infection diagnosed before age 12 weeks and CD4

>25%(All get CTX and pneumococcal vaccine)

ART* start (or restart) when CD4 <20%** or severe CDC Stage B or C disease occurs

ARM 1ART* defer

until neededN=125

ARM 2Short-course

40 weeksof ART*

(until ~1st birthday)N=125

ARM 3Longer-course

96 weeksof ART*

(until ~2nd birthday)N=125

Follow-Up forMinimum 3.5 Years

*ART = AZT/3TC/LPV/r**August 2006 changed to <25%

Continuous ART1st Line

2nd LineART

Start 1st Line ART

Continuous ART1st Line

2nd LineART

2nd LineART

Continuous ART1st Line

Start 1st Line ART

Delay ART

Until Needed

ART Interruption

Until Needed

Arm 1: Delayed ART Until Meet Standard Criteria

Arm 2: Immediate ART at Age 6-12 Weeks until Age 1 Year (ART-40 weeks)

Arm 3: Immediate ART at Age 6-12 Weeks until Age 2 Years (ART-96 weeks)

CHER Schematic Representation of Study Treatment Strategies

ART Interruption

Until Needed

CHER: Early HAART Significantly Reduces Mortality and Disease Progression

Violari A et al. NEJM 2008;359:2233-44

P = 0.0002

76% Reduction in Mortality:

4% vs 16% forEarly vs Deferred

ART

Probability of Death

Probability of Death or CDC Severe B/C Disease

Most deaths occurred within first 6 months

p<0.0001

p<0.0001

16%

4%

26%

6%

Early HAART in HIV-Infected Infants Associated with Improved Neurodevelopmental Outcome: CHER and Control Children

Laughton B et al. AIDS. 2012;26(13):1685-1690.

Characteristic

Deferred ART

Early ART

HIV-exposed

uninfected

HIV-

unexposed

P Value

Number 26 66 28 34

Median age 11 11 11.4 11.5

Mean Motor ±ISD

88.9 ± 16/3

97.6± 12.5

105.3± 14.3

101.6± 13.7

0.01

Mean General Quotient ±ISD

100.1 ± 1.38

106.3± 10.6

106.0± 10.1

106.9 ±1 1.7

0.02

Griffiths Mental Development Scales given between age 10-15 months to deferred vs early patients, HIV-exposed uninfected, & HIV-unexposed children

CHER: Time to Starting Continuous ART Cotton M et al. 19th CROI, Seattle, WA, March 2012 (Abs 28LB)

CHER: Distribution of Primary Endpoints by Study ArmCotton M et al. 19th CROI, Seattle, WA, March 2012 (Abs 28LB)

ART-Deferred (N=125)

ART-40 Wks(N=126)

ART-96 Wks(N=126)

Total events 39 (31%) 31 (25%) 25 (20%)

Death 22 (18%) 11 (9%) 9 (7%)

Clinical failure 8 (6%) 6 (5%) 5 (4%)

CDC Severe B 5 (4%) 1 (1%) 2 (2%)

CDC C 3 (2%) 5 (4%) 3 (2%)

Immune failure 9 (7%) 14 (11%) 11 (9%)

<20% by wk 24 4 (3%) 7 (6%) 5 (4%)

<20% x 2 at >wk 24 5 (4%) 7 (6%) 6 (5%)

Regimen-limiting ART toxicity

0 0 0

Change to 2nd line ART 3 3 1

CHER: Time to Primary Outcome (Death or Failure 1st Line) ART-Deferred vs ART-40 wk and/or ART-96 wk

Cotton M et al. 19th CROI, Seattle, WA, March 2012 (Abs 28LB)

CHER: Time to Primary Outcome (Death or Failure 1st Line) ART-40 wk vs ART-96 wk

Cotton M et al. 19th CROI, Seattle, WA, March 2012 (Abs 28LB)

CHER: Disease Progression (Severe B or C) or DeathART-Deferred vs ART-40 wk vs ART-96 wk

Cotton M et al. 19th CROI, Seattle, WA, March 2012 (Abs 28LB)

CHER: SummaryCotton M et al. 19th CROI, Seattle, WA, March 2012 (Abs 28LB)

Early ART until 1st or 2nd birthday followed by interruption compared to deferred ART:

Appears safe in children with regular CD4 and clinical monitoring Reduces mortality by ¾ and reduces disease progression Has less ART exposure (potential cost-saving)

Early ART for 2 years compared to 1 year results in:

Similar ART exposure Longer subsequent interruption Trend toward fewer clinical events

Few children required switch to 2nd line ART.

Further analysis needed to evaluate viral suppression, resistance

and immune response after ART restart.

The International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Mission/Aims Develop and evaluate safe, cost effective approaches

to interrupt mother-to-child transmission (MTCT)

Evaluate treatments for HIV-infected children, adolescents, and pregnant women, including treatment and prevention of co-infections and co-morbidities

Evaluate vaccines for prevention of MTCT and sexual transmission among adolescents, and for therapeutic use

IMPAACT Leadership Group IMPAACT has a leadership group consisting of 5 scientific

committees that develop and prioritize the science/protocols which are then implemented by 39 domestic and 34 international clinical trial units PMTCT Primary Therapy Complications Vaccine/IBT Women’s Health

IMPAACT is supported by SDMC, Operations Center, and Central Lab Group (4 virology, 4 immunology, 4 pharmacology, 1 genetics specialty labs) and approximately $65 million/yr total in funding

IMPAACT National Institute of Allergy and Infectious Disease (NIAID) Funded Sites

13 Domestic, 25 International Clinical Research Sites

IMPAACT Eunice Kennedy Shriver National Institute of Child Health Development (NICHD) Funded Sites

23 Domestic, 10 International Clinical Research Sites

Choose the FALSE statement about global mortality in children under 5 during 2008:

A. Approximately half of the nearly 9 million deaths occurred in Africa

B. Rotavirus is the leading cause among diarrheal-related mortality

C. Malaria accounts for approximately 1/3 of deaths in Africa among this group

D. Respiratory illness is the leading cause of mortality A. B. C. D.

0% 0%0%

100%

Global Childhood Mortality in 2008

8.795 million estimated deaths in children <5 yr of age (half in Africa)

18% or 1.575 million deaths due to pneumonia (S. Pneumoniae, TB, RSV)

15% or 1.336 million deaths due to diarrhea (rotavirus is leading cause)

8% or 732 thousand deaths due to malaria (16% in Africa)

Black RE et al Lancet 2010;375:1969-1987

Burden of HIV WHO estimates that 367,000 infants were

infected with HIV in 2009

40% of new “adult” infections occur in youth 15 - 24 yrs

If we meet WHO goals (90% women/infants receive VCT and ARV prophylaxis with regimens capable of reducing MTCT to <5%), still 138,000 new infections yearly in 25 countries

Infants and Children Differ from Adults Well characterized timing of acute infant infection Immune responses not fully developed in infants Disease progression; HIV - 40% survival at 2 yr, w/o Rx Functional thymus – immune reconstitution Pharmacokinetics – absorption, distribution, clearance Ontogeny of renal and hepatic function Growth and development – including neurodevelopment;

still unknown impact of HIV, ARVs Potential duration of ARV need, 70-80 years Challenges of TB diagnosis Increased severity of malaria

Adolescents and Pregnant Women Differ from Non-Pregnant Adults

Adolescents Pubertal development; impact of HIV-1 and ARVs

Risk-taking behavior; behavioral disinhibition

Adherence to medications

Pregnant Women Increased risk of acquisition and transmission of HIV-1

Pharmacokinetics; absorption, distribution, clearance, binding

Adverse events; preeclampsia, fetal loss, congenital anomalies

Alterations in immune function, transplacental antibodies

Higher risk of severe disease and mortality (H1N1, malaria)

Past Accomplishments of the Pediatric/Maternal HIV-1 Networks

Preventing vertical transmission of HIV-1 Providing data for licensure of drugs for infants,

children and adolescents with HIV and dosing recommendations for pregnant women

Developed and validated diagnostic testing for infant HIV infection

Evaluating vaccine safety and immunogenicity in HIV infected pregnant woman, adolescents and children and other pediatric populations

Antiretroviral Drugs Approved in Adults

N(t)RTI NNRTI ProteaseInhibitors

Entry/Fusion Inhibitors

Integrase Inhibitors

Abacavir Efavirenz Atazanavir Enfurvirtide Raltegravir

Didanosine Nevirapine Darunavir Maraviroc Elvitegravir*

Emtricitabine Etravirine Fosamprenavir GSK572

Lamivudine Rilpivirine Amprenavir

Stavudine Indinavir

Tenofovir Lopinavir/rtv

Zidovudine Nelfinavir

Ritonavir

Saquinavir

Tipranavir

Efficacy data provided

Which of the following antiretroviral agents is NOT approved for children under 12 yrs:

A. Abacavir

B. Tenofovir

C. Efavirenz

D. Maraviroc

E. Etravirine

A. B. C. D. E.

0%

100%

0%0%0%

ARV Pediatric Labeling Influenced by IMPAACT Studies

N(t)RTI NNRTI ProteaseInhibitors

Entry/Fusion Inhibitors

Integrase Inhibitors

Abacavir Efavirenz Atazanavir Enfurvirtide Raltegravir

Didanosine Nevirapine Darunavir GSK 572

Emtricitabine Etravirine Fosamprenavir

Lamivudine Amprenavir

Stavudine Lopinavir/rtv

Tenofovir Nelfinavir

Zidovudine Ritonavir

Tipranavir

Approval or label dosingEfficacy data providedUnder study in IMPAACT* for pMTCT

Vaccines in Children, Adolescents and Pregnant Women in IMPAACT Studies

MMR*

Varicella

Pneumococcal*

DTaP

HPV (girls and boys)

Hep A

Hep B

Rotavirus*

H1N1

Seasonal Influenza

Meningococcal

HPIV3*

TB*

HIV-1*

Red font indicates vaccines also studied in pregnant women* Indicates vaccine studied in children less than 2 years old

Current IMPAACT Studies

EtravirineGSK 572RaltegravirTenofovir/newborn

Efavirenz/infants/TBAtazanavir

Pregnancy PKViral decay late pregnancyARV PK interactionsWeight band dosing LPVARVs malnutrition

FTC monotx bridgeSimplification/adolsNVP vs LPV/r infantsNVP/breastfeedingPROMISE*Infant prophylaxis

IRISMicrobial translocationGenomicsReservoirs

Bone ΔsPIs malariaHIV Ther Vx(adol)

AlendronateBedaquiline MDR-TBH1N1 vaccine kidsH1N1 pregnancyHPIV-3 infants/kids

AtorvastatinPneumococcal Vx pregHPV Vx kidsARV/anti-malarial interactARV/anti-TB interactARV/psychotropic interact

INH/pregnancyRotavirus VxMeningococcal VxHBV Vx adolsHPV Vx adols

* indicates study with greater than 8000 subjects

PathogenesisTranslational Phase I/II Phase II Phase III

ARV

Com

plic

ation

s

PROMISE – Addresses 4 key questions

What is the optimal intervention for the prevention of antepartum and intrapartum transmission of HIV? (Antepartum Component)

What is the optimal intervention for the prevention of HIV transmission in breastfeeding infants? (Postpartum Component)

What is the optimal intervention for the preservation of maternal health after the risk period for MTCT ends (either at delivery or cessation of BF)? (Maternal Health Component)

What is the optimal intervention for the prevention of the infant morbidity and mortality associated with BF cessation? (Infant Health Component)

Promoting Maternal and Infant Survival Everywhere

AP 14 wks-term IP PP for Duration BF Weaning

CD4>350Continue Triple ARV Regimen

Infant NVP Prophylaxis

AZTAZT+

sdNVP+TRV tail

Triple ARVProphylaxis

Stop All ARVs

Triple ARV Prophylaxis

Triple ARV

Prophylaxis Mother

Randomize

Randomize

Randomize

Late presenters

AZT+sdNVP+

TRV tail

Infant uninfected at birth

Implemented Q1 2010: 1700 enrolled

IMPAACT Future Research Priorities Pediatric vaccine studies (HIV infected and other pediatric

populations) Aeras recombinant BCGs and adeno-vector vaccines for TB; safe and

immunogenic? HPIV3, RSV, HSV vaccines in development; safe and immunogenic? Malaria vaccines in development; e.g. irradiated sporozoites

Safety/PK of new ARVs/formulations, TB, other drugs in children & pregnant women; drug-drug interactions

Improved diagnostic tests for infants and children Assays to diagnose TB in children using accessible body fluids such

as blood, urine, stool. Innovative point of care diagnostics for other pathogens.

HIV prevention strategies in adolescents internationally What are optimal strategies for PrEP in adolescents?

IMPAACT Future Research Priorities Prevention/treatment of Co-infections (HCV, HBV, TB) Treatment of co-morbidities and effects of chronic ARV use in

children Safety/PK and efficacy of Atorvastatin to treat lipodystrophy? Drug-drug interactions between ARVs and psychotropic meds?

Prevention of MTCT and treatment of pregnant women Pathogenesis-based evaluation of failures of prophylaxis Prevention of incident infection during pregnancy and breastfeeding

Immune/inflammatory response Pathogenesis research in acutely infected newborns that can lead to

development of a cure strategy. Define and ameliorate the inflammatory response that causes

morbidity such as IRIS, non-AIDS events in children & pregnancy.

NIH Scientific Priority Areas for HIV Peds and Maternal Health

Prevention of HIV Acquisition

Cure and/or Functional Cure

Pharmacology, Drug Formulation and Novel Interventions

Co-infections, Co-morbidities and ART Consequences

Vaccines of High Priority to these Populations

Prevention of HIV Acquisition Collaborate on bridging studies in adolescents to evaluate the

safety, feasibility and efficacy of microbicides, PrEP and HIV vaccines: Protocols on safety/efficacy of tenofovir gel and other microbicides

(e.g. VRC monoclonal Ab) in young women

Evaluate testing strategies and interventions for incident infection in pregnant and breastfeeding women to prevent transmission to their infants: Protocols to evaluate safety and efficacy of oral/microbicide PrEP in

pregnant and lactating women

Evaluate any high priority emerging questions related to mother-to-child transmission: Prevention MTCT of TB, HCV, HBV and drug safety in pregnant

women/fetus in HIV infected pregnant women.

Cure and/or Functional Cure Evaluate novel strategies to prevent development of viral

reservoirs specially in the unique context of the known timing of intrapartum transmission

Within the context of clinical trials:

Quantify viral reservoirs

Especially in newborns (in utero & perinatal infection)

Investigate host, viral or other factors that influence the size and development of viral reservoirs

In recently infected newborns

Evaluate tools to investigate reservoirs

Viral, immunological, genetic assays to assess body compartments using body fluids, biopsy and autopsy

Pharmacology, Drug Formulation and Novel Interventions

Determine the safety and optimal dosing of new ARVs and drugs for related infections

Especially in pregnant women, young children and infants

Elucidate drug-drug interactions involving ARVs and medications to treat co-infections and co-morbidities

TB, malaria, hepatitis in children and pregnant women

Evaluate highly innovative drug formulations and delivery platforms

e.g. Sprinkles and medication patches in infants and young children

Evaluate novel anti-HIV compounds, therapeutic vaccines and other interventions aimed at ameliorating the effects of HIV infection

Co-infections, Co-morbidities and ART Consequences

Investigate interventions to treat and prevent co-morbidities, co-infections and ART consequences

Prevention and treatment of co-morbidities and effects of long-term ARV use in children (neurodevelopmental, growth, psych, renal, lipodystrophy)

Novel vaccines and drugs to prevent TB, PK studies of new TB drugs, evaluation and treatment of MDR TB

Evaluate non-invasive and reliable strategies to diagnose TB and other infections in children

e.g. Cepheid Xpert (NAAT-based) TB assay

Evaluate strategies to prevent mother-to-child transmission of HIV related infections such as TB and hepatitis

e.g. Newly licensed anti-HCV drugs

Within the context of interventional research, address the impact on HIV pathogenesis and disease progression of

Immune activation, inflammation, and immune senescence and strategies to reconstitute immunity

Role of microbial translocation, IRIS, immune development/senescence and CVS disease (children vs adults), ARVs and immunomodulators in children

Other chronic viral infections

HBV, HCV, HPV and EBV

Genetics and other host factors

Pharmacogenomics, HIV susceptibility

Co-infections, Co-morbidities and ART Consequences

Vaccines of High Priority to HIV-infected Children and Pregnant Women

Determine the safety and immunogenicity of licensed and other high priority vaccines in HIV-infected children

TB, HCV, HBV, HPV, HSV, RSV, malaria and influenza

Determine the safety of licensed and other high priority vaccines in HIV-infected pregnant women and investigate transplacental infant protection

e.g. PCV

Summary The pediatric and maternal HIV networks have

accomplished significant milestones in PMTCT, advanced ARV management for HIV-infected children and pregnant women and spearheaded vaccine safety and immunogenicity efforts for these populations

Much research remains to be done in pediatric and maternal HIV and other infectious diseases affecting these populations

IMPAACT is uniquely poised with its clinical infrastructure, access to site populations and leadership/site expertise to address and advance key aspects of pediatric and maternal health

The Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN)

ATN’s Scientific Leadership and Agenda

Select the TRUE statement regarding domestic HIV epidemiology in 2009:

A. The incidence of HIV infections among Hispanic males is similar to that of White males

B. The largest proportion of new HIV infections occurred among 13-29 year olds

C. New HIV cases among African Americans were equally high between males and females

D. The proportion of new HIV infections among youth 13-29 who were unaware of their infection status was 21%

A. B. C. D.

0% 0%0%

100%

Domestic Burden of HIV

*Centers for Disease Control and Prevention, 2011

Domestic Burden of HIV

*Centers for Disease Control and Prevention, 2011

Adolescents ≠ Adults or Children Genetics

Environment

Adherence

Pharmacokinetics

absorption

Pharmacokinetics

distribution

Pharmacokinetics

biotransformation

excretion

Physical maturation

Tanner stages 1-5

Sexual maturation

Adrenarche

pre-Tanner

Psychosocial & Cognitive Maturation

Pharmacodynamics

Behavioral issues

Smoking, alcohol, marijuana, OCPs...

OCPs – Oral contraceptive pills

Modified after Rogers, A: Pharmacologic Considerations. In Friedman SB, editor: Comprehensive Adolescent Health Care, ed 2, Elk Grove Village, IL, 1998, American Academy of Pediatrics, p 96.

Genetics

Environment

Adherence

Pharmacokinetics

absorption

Pharmacokinetics

distribution

Pharmacokinetics

biotransformation

excretion

Physical maturation

Tanner stages 1-5

Sexual maturation

Adrenarche

pre-Tanner

Psychosocial & Cognitive Maturation

Pharmacodynamics

Behavioral issues

Smoking, alcohol, marijuana, OCPs...

OCPs – Oral contraceptive pills

Modified after Rogers, A: Pharmacologic Considerations. In Friedman SB, editor: Comprehensive Adolescent Health Care, ed 2, Elk Grove Village, IL, 1998, American Academy of Pediatrics, p 96.

Adolescents ≠ Adults or Children

Can’t simply scale up/down dosing of meds

Physical changes in adolescence can result in unpredictable parameters that may not change consistently with age, developmental stage or metabolic function

Medication dosage may be

adequate and not require adjustment toxicsub-therapeutic

Only through carefully controlled clinical research among youth can appropriate regimens/doses of a variety of medications and treatment strategies be determined

Barriers to care and participation in research involve

Behavioral issues and adherence challenges due to Eating disorders

mood disorders

substance use

other risk-taking behaviors

poor psychosocial support systems/coping behaviors

instability of home environment/housing

Adherence issues can present barriers in a variety of settingsMedical/Research visits

Medications/Study Interventions

Non-pharmacologic/biomedical treatment interventionsPsychotherapy

Substance use rehabilitation

Risk reduction counseling

Inability to pay for services and products without inadvertent parental disclosure

Adolescents ≠ Adults or Children

Under which of the following circumstances is it MOST APPROPRIATE to disclose a youth’s PHI to their parent/guardian?

A. The new diagnosis of HIV infection and AIDS in a 17 year old boy who you are concerned may not follow up for care, placing his health in jeopardy and risking a secondary transmission to his new boyfriend

B. The provision of HIV PEP to a 16 year old young woman, whose 1st date forced sexual activity the evening prior

C. The diagnosis of major depression in a 16 year old young man who has been recently diagnosed with HIV infection

D. The provision of HIV PrEP to an 18 year old young man who is on his father’s health insurance policy and has admitted to several casual anonymous encounters of UAI in the past 3 months

A. B. C. D.

0% 0%0%0%

Adolescents ≠ Adults or Children

Other barriers to care and participation in research involve

Consent issues and evolving decisional capacity

Right to autonomy vs impaired judgment

Ethical concerns given vulnerable population

Legal and jurisdictional definitions and guidance

Regulatory guidelines and access to care/research

Biologic issues and physiologic variances

Drug metabolism

Child-bearing potential

Adolescent Issues in Community Preparation for Trials

Effective social and behavioral interventions serve as foundation for biomedical prevention trials ATN secures community assent through building a prevention infrastructure.

Developing partnerships that build on the diverse insights and skills of researchers and the community to select culturally responsive and research-based interventions to meet the needs of the community’s youth

®

Primary Prevention Project: C2P® Phases of Implementation

Phase I: Building community capacity, identifying intervention venues and populations

Map local epidemiology of HIV infection in adolescents.

Phase II: Social network interviews & venue-based HIV testing

Establish partnerships with community agencies who work with at-risk youth.

Identify recruitment venues for highest risk youth.

Phase III: Intervention Implementation

Identify communities’ prevention priorities and select responsive interventions.

C2P® Phase I – Community Partnership Building & Identifying Intervention (high risk) Venues

Connect to Protect (C2P®) Phase II (2004-2006) Venue Surveys

Venue-based needs assessment conducted for at-risk youth 12-24

Recruited at 4 venues per city over 3 months

Anonymous computerized, self-administered surveys + Oral antibody testing for HIV

Increase participation

Reduced harm

Increase validity

Referred for confidential testing

HIV Rates Among 12-24 Year Olds from US Urban Venues, 2004-2005

Barnes, et al. Arch Pediatr Adolesc Med. 2010 Mar;164(3):273-6.

60% of HIV-infected males where previously unaware of their infection

C2P® Phase III – Community Mobilization for Structural Change

Goal of C2P® is to

Create a prevention platform to conduct

Vaccine trials

Microbicides

Pre-exposure prophylaxis (PrEP)

Other biomedical prevention interventions

Through….

Primary Prevention Project: C2P® Phases of Implementation

Phase I: Building community capacity, identifying intervention venues and populations

Map local epidemiology of HIV infection in adolescents.

Phase II: Social network interviews & venue-based HIV testing

Establish partnerships with community agencies who work with at-risk youth.

Identify recruitment venues for highest risk youth.

Phase III: Intervention Implementation

Identify communities’ prevention priorities and select responsive interventions.

ATN’s Community Prevention AgendaThe Connect-to-Protect Program

Addressing the Continuum of Care for HIV-infected Youth

The Linkage & Engagement to Care Continuum

Crisis Management

Distress / Suicidality

Mental Health

Housing

Readiness for care /

Acceptance of diagnosis

Clinical Care

Staff Case Management

Outreach

Collaboration with testing & ATN staff

Tracking transition from referral

source & maintaining continuity

Addressing Barriers

Eligibility for Services

Ongoing Staff-Patient Communication

FinancesTransportation

Parental PermissionCitizenship

Social Support – Medical Buddy

Disease Status /Medication

Management

Patient Education / Orientation

Patient Motivation / Hope

Detailed Counseling

Face to face

Telephone

Reading Materials

An Integrated Model of Transitions in HIV-related Prevention, Diagnosis & Treatment

Prevention Networks

None

Public Health SystemHealth Care System

Testing Networks

Youth Treatment NetworksAdult

Treatment Networks

Infection LTC Engagement in Care Retention in Care Youth to Adult Care

Prevention Testing LTC Case management and retention Transition

HIV risk behaviorsHIV prevention behaviors

HIVTCHIV test RR+

AppointmentAdherence

MedicationAdherence

Secondary PreventionAdherence

AdultHealth Care

Years Months to Years Months Months Years Lifelong

Greatest Reduced ReducedLess Least

Systems

Networks

Services

Risk of

Transmission

Events

Timeline

Behaviors

CDC-ATN Collaboration: Specific Objectives forSMILE in CARING for YOUTH

Improve identification of recently HIV-infected adolescents and young adults in the U.S.

Facilitate a practical and meaningful linkage to care at local AMTUs for HIV-infected youth

Ensure engagement and maintenance of care for HIV-infected youth at local AMTUs

Conduct programmatic and process evaluations and measures to determine effectiveness of these endeavors.

PROGRAM

RESEARCH

CDC-ATN Collaboration: Design ofSMILE in CARING for YOUTH

The identification of HIV infected individuals occurs within local clinics, hospitals, and programs supported by local health departments via CDC.

Collaborating agencies established referral relationships with the AMTUs to identify HIV infected youth and connect these individuals with an ATN outreach expert.

Details implemented on a case by case basis to ensure that the appropriate grantees (both sides) are involved in the planning and implementation of the program, and the evaluation processes (ATN research protocol).

NIH / NICHD

CDC

NY

MD

DC

PA

IL

TN

LA

CA

FL

14 US AMTUs

13 US HEALTH DEPTARTMENTS

DOHDOH

DOHDOH

MA

MI

CO

TX

CDC-ATN Collaboration: Progress (2010-Now)SMILE in CARING for YOUTH

Non-LTCN=635

New Cases = 1674

Summary

• There are unique barriers and challenges both on the clinical front line as well as in engaging youth to participate in clinical research.

• New HIV infections remain alarmingly high and are increasing among youth and MSM of color.

• The ATN is the nation’s only research network devoted entirely to HIV-infected & at-risk youth, 12-24 years old.

• ATN has a broad research agenda focusing on primary, secondary and tertiary prevention.

• Only through well-desgined and coordinated comprehensive approaches for treatment and prevention among youth will we be able to improve treatment outcomes and stem the tide of new HIV infections.