1. Growing up with HIV in resource-rich countries: a case report Rohan Hazra, M.D. Pediatric, Adolescent and Maternal AIDS Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Department of Health and Human Services July 25, 2012

2. Case report 10 year old perinatally HIV-infected male referred for “salvage therapy.” Past medical history notable for recently treated Burkitt’s lymphoma

3. Cancers in HIV-infected children: CDC PSD and LEGACY Cohorts N=5,735; 37,240 person-years Twichell, CROI 2010, #859 * <.05

4. Case report 10 year old perinatally HIV-infected male referred for “salvage therapy.” Past medical history notable for recently treated Burkitt’s lymphoma Diagnosed with HIV at 2 months of age. Began ZDV at 33 months of age (CD4 288).

5. Sequential unsuccessful ART ZDV/3TC ZDV/3TC/RTV ZDV/3TC/NFV ddI/d4T/NFV ddI/d4T/NVP ddI/d4T/RTV d4T/EFV/RTV/SQV ddI/APV/LPV/r

6. Other medical history Varicella h/o +PPD, received INH Paresthesias with d4T/EFV/RTV/SQV Pancreatitis with ddI/APV/LPV/r ADHD diagnosed at 10 years of age

7. Project CASAH (Child and Adolescent Self-Awareness and Health) Mellins, J Child Psychol Psychiatr 2009 Types of psychiatric and substance use disorders in 9-16 year old children affected by HIV in NYC (206 HIV+ and 134 HEU) The Diagnostic Interview Schedule for Children (DISC-IV) – caregiver OR youth report

8. Project CASAH (Child and Adolescent Self-Awareness and Health) Mellins, J Child Psychol Psychiatr 2009

9. Other studies P1055 (Gadow, JDBP 2010) and PHACS (Malee, Aids Care 2011) P1055: 6-17 y, 319 HIV+, 174 HEU, and 82 negative in HIV+ household DSM-based instruments and other surveys Psychopathology - no substantial differences between groups PHACS: 7-16 y, 295 HIV+, 121 HEU Behavioral Assessment System for Children (BASC-2)

10. When we saw him Completed therapy for Burkitt’s 7 months ago. Off ARVs during chemotherapy. ddI/APV/LPV/r stopped after one month 5 months ago CD4: 1%/4, VL 385k Extensive, multiclass resistance

11. Response to ART TDF/ZDV/3TC/LPV/r

12. Complications Anemia – ZDV replaced with d4T Nephrolithiasis Elevated fasting cholesterol and triglycerides and lipoatrophy

13. Hypercholesterolemia Rates in HIV-Infected Children: Cholesterol >200 mg/dL Euro Pediatr Lipodys Grp, AIDS 2004 Carter, JAIDS, 2006 Rosso, Eur J Endocrinol 2007 Chantry, Pediatrics 2008 Aldrovandi, AIDS 2009 Brewinski, J Trop Pediatr, 2010 Dimock, Metabolism 2010 Sztam, J Pediatr Gastroentrol Nut, 2011

14. Bone Mineral Density by DXA Thomas, CROI 2009

15. Bone Mineral Density by DXA Thomas, CROI 2009

16. Bone Mineral Density (BMD) in HIV-Infected vs HIV-Uninfected Children by Gender (P1045) Jacobson D et al, AIDS 2010;24:587-96 236 HIV-infected and 143 uninfected youth 7-24 years of age Appearance of significant and widening difference in BMD for HIV+ vs HIV- BOYS over course of pubertal progression (adjusted) Similar pattern but non-significant differences in GIRLS HIV - HIV+ HIV - HIV+

17. Renal Health Andiman, PIDJ 2009: 2102 children in PACTG 219/219C – renal abnormalities associated with non White race, older age, TDF Judd, AIDS 2010: 456 children in UK/Ireland CHIPS cohort- decreased renal tubular function associated with prolonged TDF

18. Insulin Resistance Geffner, Hormone Research in Pediatrics 2011 402 ARV-treated perinatally-infected youth (mean age 12 y, 25% prepubertal) 61 (15.2%) – insulin resistance Association with obesity was stronger than for any other variable

19. Young man in his early 20s Perinatally-acquired HIV Cancer Insulin resistance High cholesterol ADHD History of low bone density Renal disease

20. Young man in his early 20s Perinatally-acquired HIV Cancer Insulin resistance High cholesterol ADHD History of low bone density Renal disease High school graduate Employed A survivor Resilient Potential for a full and productive adulthood