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 ARTUntil Needed
ART InterruptionUntil 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 InterruptionUntil 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 34Median age 11 11 11.4 11.5Mean 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 AdultsN(t)RTI NNRTI Protease
InhibitorsEntry/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 NelfinavirRitonavir
Saquinavir
Tipranavir
Efficacy data provided
Which of the following antiretroviral agents is NOT approved for children under 12 yrs:
A. AbacavirB. TenofovirC. EfavirenzD. MaravirocE. 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*VaricellaPneumococcal*DTaPHPV (girls and boys)
Hep AHep B
Rotavirus*H1N1Seasonal InfluenzaMeningococcalHPIV3*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-TannerPsychosocial &
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-TannerPsychosocial &
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 beadequate 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 involveBehavioral issues and adherence challenges due to
Eating disordersmood disorderssubstance useother risk-taking behaviorspoor psychosocial support systems/coping behaviorsinstability of home environment/housing
Adherence issues can present barriers in a variety of settingsMedical/Research visitsMedications/Study InterventionsNon-pharmacologic/biomedical treatment interventions
PsychotherapySubstance use rehabilitationRisk 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 populationLegal and jurisdictional definitions and guidanceRegulatory guidelines and access to care/research
Biologic issues and physiologic variancesDrug 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 trialsMicrobicidesPre-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 System Health 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 HIVTC HIV 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 AMTUs13 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.