Download Perinatally Infected Adolescents:

A Pediatric Review of the
HIV Disability Criteria
Andrew Wiznia, M.D.
Director, HIV Services
North Bronx Healthcare Network
PI. NBHN Pediatric HIV Clinical Trial Unit
Professor of Pediatrics
Albert Einstein College of Medicine
9/10/08
Pediatric HIV
Update
• Three unique Pediatric Populations
– Vertically infected
– Adolescents infected through high risk
activities
– Others: accidental needle sticks, nonconsensual sex,
• Contaminated blood products—clinical course
similar to vertically infected
• US: maternal-infant transmission rate about
1%; approximately 250 infected babies/yr
• Aging perinatal population involved in atrisk behaviors
Pediatric HIV
Update
• Changing natural history
• Fewer numbers, therefore harder to develop
pediatric specific, peer reviewed incidence,
prevalence and sequelae data
• Many large longitudinal studies in US are no
longer being funded
HIV Infected Patients
Jacobi Medical Ctr. 2002 - 2008
200
2002
2005
2008
180
160
Patients
140
120
100
80
60
40
20
0
<2
2-4
5-8
9 - 11
Ages (yrs)
12 - 14
15 +
Pediatric HIV ARV Treatment
• Perinatally acquired
– Many initially treated with multiple mono and
dual ARV therapy regimens prior to HAART
– These regimens were non-suppressive, selected
for resistance to drug and other agents in that
class
– As newer agents developed, lag in development
of pediatric formulations, dosing and safety
data
– Despite lack of pediatric indication, most ARVs
are rapidly and widely prescribed for children
• At what cost?
Pediatric HIV ARV Treatment
• Consistent adherence to regimens is constant
challenge
– Obstacles: Different developmental stages, schools,
peers, disclosure, toxicity, palatability
– Result: Extensive resistance and fewer options
– Approximately 50% are taking “salvage” regimens
• Salvage: typically complex (3-5 drugs); increasing toxicity
• Frequently not adequately potent to suppress HIV replication
• Adolescents infected through high risk activity:
treatment is potentially simpler due to improved
therapies, fixed dose combinations, little baseline
resistance, others
Adolescent Brain Development
Perspectives of an immunologist
• Limbic System: First part of brain to develop
• Limbic System= Raw emotionin overdrive in adolescents-hormone related
• Cerebral cortex, the judgment center, is the last
part of the brain to develop
• Immaturity of cerebral cortex coupled with a
hyperactive Limbic System leads to Poor
Judgments
• Result is Risk Taking behavior driven by pleasure
centers and a sense of immortality.
Unique Issues for HIV-infected
Adolescents/Young Adults
• Psychosocial
– Predominately affects an urban minority population
facing numerous socioeconomic challenges
– Lack of resources: home, school, mentors, friends
– Transitioning from an incurable illness to a chronic care
model
• True familial illness: Generational HIV,
• Familial loss—Leading to the perception of life defined by
abandonment:
– Many mothers, fathers and others have succumbed to
the illness
– Many children are products of foster care system
– Numerous changes in guardians and less stability in
“parental” care
More Unique Issues for HIV-infected
Adolescents/Young Adults
• Life characterized by other LOSS and
stigmatization
– Loss of health during childhood
– Loss of being treated as a normal child—
overprotection, lack of consistency, being
coddled as expected life expectancy was
perceived as limited
– Loss of ability to experiment: Relationships,
SEX, Drugs, Ethanol
– Loss of “being or looking normal”
• Potential for disconnect between reality and the
perception of an adolescent
• Great impact on function
Major Task: 2008
• Transitioning from:
– Being defined by a poorly treated illness
perceived as progressive with a shortened life
expectancy
– Having few expectations or responsibilities
TO
– A chronic illness that is treatable with an
unknown but increasing life expectancy
• Personal redefinition: Transition from being
defined by HIV to being defined as an
individual living with HIV
114.08 Human
immunodeficiency virus (HIV)
Pediatric Infection.
Comments and Potential
Modifications
Bacterial Infections
114.08 A
• 1. Mycobacterial infection-disseminated
–
–
–
–
An issue, but not common
Immigrant populations from endemic areas
MDR, XDR
Treatment complicated by lack of pharmacokinetic and
drug:drug interaction data
• Nocardia
– Very uncommon, ?? Relevance
• Salmonella bacteremia, recurrent—still relevant
• MRSA/VRE-likely to become more problematic,
especially with prolonged immunodeficiency
Recurrent Bacteremia
• Recurrent bacteremia-not CD4 dependent
– Distinction between low CD4 and immune dysfunction
• Current: < 13 yrs of age, multiple or
recurrent (2x per 24 mos) pyogenic
bacterial infections,
• Multiple or recurrent (3 per 12 months) bacterial
infections (including PID) with hospitalization or
IV antibiotics
• Proposed: no age difference
• Proposed: Add chronic skin infections which may
be considered disfiguring and interfere with
expected activities
Fungal Infections
(114.08 B)
• Candidiasis
– Current: Includes pharyngeal, esophageal,
vulvovaginal and others
• most are well controlled with short courses of oral
antifungal agents
– Proposed: add time, frequency or severity
standard
• >2/yr each or persist for >15 days post therapy
• acute weight loss (>5% from baseline)
• Despite treatment, persistent inability to swallow
foods or medications, unable to phonate
Other Fungal
(114.08 B)
• PCP: Still a great concern
– Fewer cases in infants due to fewer infected babies and
prophylaxis guidelines for HIV exposed infants
– Increasing incidence in aging children, adolescents, and
young adults due to poor virologic control, worsening
immunodeficiency (adherence, few ARV options,
behavioral patterns)
– Proposed: no change
• Current: many listed occur infrequently, if at all
– Aspergillosis (if very ill, pulm is seen)
– Coccidioidomycosis
– Mucormycosis
Protozoan or helminthic infections
• Cryptosporidium:
– Currently, not that common
– With increased adolescent population, potential
for increased drug resistance and more
immunodeficiency
• Proposed: Add cyrptosporidium to list
– Chronic, unrelenting diarrhea problematic for
school attendance, other activities
– difficult to treat, lack of available agents with
limited peds indications, debilitating in school
Viral Infections (114.08 D)
• Herpes simplex and varicella
– Many respond to treatment
– Resistant or persistent despite treatment can be
disabling
– Definition of resistant must consider lack of
adequate response over period of time as well
as location of lesions and how they affect
quality of life (patient perception)
• Threshold for disfigurement for adolescents may be
different than for adults (peer pressure, etc.)
• Also hold for 114.08 F
• One month may be excessive
Neoplasia (114.08E)
• Literature is still sparse
• Children: 10 fold increase in neoplasia; across
spectrum of CD4 counts
• Progressive immunodeficiency assoc with
increased risk of neoplasia, many uncommon
• Need to allow flexibility for rare neoplasia, as well
as changes in types and prevalence, including anal
carcinoma, Kaposi’s, others
• Carcinoma of the cervix, invasive, FIGO stage II,
is seen in adolescents
Neurological manifestations
(114.08 G)
• Current (and need to continue):
– Loss of previously acquired- or
– marked delay in achieving, developmental
milestones or intellectual ability (including the
sudden onset of a new learning disability)
– Impaired brain growth
– Progressive motor dysfunction
114.08 H-J
• Growth Failure (114.08 H)-No change
• Diarrhea (114.08 I), lasting for 1 month or longer,
resistant to treatment- No change
• Lymphoid interstitial pneumonia/pulmonary
lymphoid hyperplasia (114.08 J)-now less
common but some older children have
bronchiectasis/chronic changes as consequence
– Proposal-use some PFT metric for entitlement
Bone Integrity
• Osteoporosis, osteopenia
– Recent reports of large numbers with bone
DEXA scan abnormalities
– Many DEXAs--2-3 S.D. below the norm
– Natural history-being studied
– Etiology
• HIV
• ARV therapies (?PI, NRTI)
• Other
• Potential Disability: Multiple fractures or
single disabling fracture
Mental Health
HIV (perinatal) infected adolescents
• About 50% live with birth parent
• Child Psychiatric Disorder
– About 66% have DSM IV diagnosis
– Almost 50% of HIV-exposed, uninfected adolescents have a DSM
IV diagnosis
• Major diagnosis
–
–
–
–
–
Depression
Anxiety
Behavioral Problems: Impulse control, ADHD
Cognitive Delay
Post traumatic Stress Disorder
• Caregiver Mental Health Problems
– Depression, Anxiety
– Problematic parent-child communication
Consequences
• High risk for poor outcomes through young
adulthood, including difficulties functioning
independently and advancing in life
–
–
–
–
–
Dropping out of school
Substance abuse, ETOH,
Incarceration
Not prepared for employment
Engaged in high risk behaviors
•
•
•
•
Their own health
Risk of transmission to others
Pregnancies
Further maternal-infant transmission
• High risk for non or intermittent adherence to
ARV
– Progressive immunodeficiency, increased viral
resistance
Mental Health Proposal
• Add new standard into adult guidelines that allows
for seamless transition of SSA benefits for HIV
infected child/adolescent into adulthood
• Standard could include a soft blend of deficits in
cognitive ability, mental health status, an
independence checklist.
• Establish realistic goals and metrics to be achieved
to encourage transition from dependence to
responsible independence
• Above incorporated into a Continuing Disability
Review (CDR) performed every 3 yrs
• Benefits: Successful transition to productive life,
maintenance of health and no need for long term
SSA benefits, less social recidivism, HIV
prevention, others
Transition into adult care
• Public Health organizations have made the
transition of care into adult systems a priority *
• Most institutions have no plan to do so
• Most clinicians lack training in this
– Most will not have to do this
• Relatively new task
• Models: CF, Sickle Cell anemia, spina bifida
– 90% reach adulthood
• Now HIV—Unique challenges
AAP, Amer Acad Family Phys, Amer Coll Phys-Amer Soc of Int Med.
Consensus statement on health care transitions for young adults with special health care needs.
Pediatrics 2002;110:1304–6.
Continuation of SSA Benefits for
aging population: New Crisis
• At 18, need to reapply for SSA benefits
• With current therapies (even if taken erratically
over time), most infected 18 yr olds are relatively
healthy and do not meet current criteria
• Many, at this age, are not emotionally equipped
for independence and are at high risk for poor life
outcomes
– vocations, school, jobs, relationships, health
• Abrupt termination of benefits is another episode
of abandonment and leaves few options
AIDS Is A Disease That Every One Hates Because
It Causes So Much Pain.
Some People With AIDS Believe In Saints.
Because It Gives Them Hope
Saints Are Like Angels With Wings
They Fly Give You Faith, Hope, and Strength.
They Make You Believe That One Day
You Can Reach The Highest Mountain,
Climb The Highest Tree and Fight
This Stupid Disease Called AIDS
15 years old, 1999
Deceased, 2008