A Pediatric Review of the HIV Disability Criteria

1. 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

2. Pediatric HIVUpdate • Three unique Pediatric Populations • Vertically infected • Adolescents infected through high risk activities • Others: accidental needle sticks, non-consensual 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 at-risk behaviors

3. Pediatric HIVUpdate • 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

4. HIV Infected PatientsJacobi Medical Ctr. 2002 - 2008

5. 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?

6. 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

7. Adolescent Brain DevelopmentPerspectives of an immunologist • Limbic System: First part of brain to develop • Limbic System= Raw emotion- in 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.

8. 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

9. 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

10. 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

11. 114.08 Human immunodeficiency virus (HIV) Pediatric Infection. Comments and Potential Modifications

12. Bacterial Infections114.08 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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 asoft 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

25. 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.

26. 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

27. 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