1. Medical and Psychosocial Characteristics of Adolescents Infected with HIV Early in Life Christos Karatzios MD CM, FRCPC  Assistant Professor McGill University Pediatric Infectious Diseases, Montreal Children’s Hospital Université de Montréal Immunologie Spéciale, Centre Hospitalier Universitaire de Mère-Enfant de l’Hôpital Ste Justine

2. Introduction HIV populations at the Montreal Children’s and Ste Justine Hospitals Descriptive Cohort Study Conclusions

3. Montreal Children’s Hospital McGill University Health Center

4. HIV at the MCH 18 total active patients Perinatal cases –17 active –Ages 4 are < 10 years old 9 are 10-14 years old 4 are > 14 years old Acquired cases –1 active 10-14 years age Neonates under investigation: –2

5. MCH Perinatal HIV cases Country of origin

6. MCH Perinatal HIV cases Current status

7. Ste Justine Hospital Centre Hospitalier Mere-enfant de l’Hopital Ste Justine Universite de Montreal

8. HIV cases at Ste Justine Active HIV: 78 Neonates under investigation: 20+ –Born to mothers HIV + Neonatal HIV - cohort: 254+ –Exposed to antiretrovirals during perinatal/neonatal period

9.  Haitian  Caucasian  African  Asian  Mulatto Ethnic origin 152 children infected with HIV Recruiting Year # # 03/05

10. 152 children infected with HIV 78 children followed 49 children died 18 children transferred or lost to follow up 7 transferred to adult Mars 2005 0 5 10 15 20 25 30 <1 yr1-5 yrs5-10 yrs 10-15 yrs 15-18 yrs >18 yrs

11. Background 27 years after HIV/AIDS was described –Remains a health problem for certain populations including adolescents well described in the earlier years of the epidemic and before the advent of highly-active antiretroviral therapy (HAART) few studies in the literature describing the current clinical and psychosocial characteristics of HIV positive adolescents a fresher look at HIV-infected youth is warranted

12. What is an adolescent? Person aged 13-21 years –The American Academy of Pediatrics Person aged 13-19 years –The World Health Organization CDC Surveillance Reports –13-14 years old –14-20 years old –20-24 years old

13. What we know… 3 groups of HIV infected adolescents: –Behaviorally-acquired HIV Sexual transmission, IV drug use –Blood product-acquired HIV –Perinatally-acquired HIV Infected at/around birth Surviving into adolescence

14. What we know… The incidence of HIV/AIDS in the US is climbing in young adults 20-24 years of age –Up 25% from 2003: 1050 new cases Half of all new infections in the US –Adolescents –Racial minorities

15. Table 1. Estimated numbers of cases of HIV/AIDS, by year of diagnosis and selected characteristics, 2003–2006—33 states and 5 U.S. dependent areas with confidential name-based HIV infection reporting  Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report, 2006 Data for 33 states Age at diagnosis (yrs) <13 211183169135 13–14 53364041 15–19 993 1,1261,332 20–24 3,1633,3683,5923,886 25–29 4,0234,0574,2364,603 30–34 5,1894,8204,6764,466 35–39 6,3695,8075,5355,442 40–44 5,7865,4295,5295,718 45–49 4,0283,8774,0284,204 50–54 2,4512,4012,5472,718 55–59 1,2791,3631,4551,438 60–64 655702692714 >65 570624613618 Year of diagnosis 2003200420052006 42095259 25%

16. Percentage of positive HIV test reports by age group and year of test, 1985-2007 Pourcentage de tests positifs pour le VIH selon le groupe d’âge et l’année du test, 1985-2007 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 1985-1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 15-19 yrs/ans 20-29 yrs/ans 30-39 yrs/ans 40-49 yrs/ans 50+ yrs/ans

17. What we know… Medical effects of HIV: –Sexually acquired HIV in teenagers Similar course to adults: most present in moderate immune suppression but are asymptomatic –Perinatally acquired HIV in teenagers Over two-thirds are symptomatic Chronic problems that impact daily living –Weight loss, recurrent opportunistic infections, chronic diarrhea, neurological disease, psychiatric disease, HIV nephropathy (African Americans), atopy (asthma) Long term non-progressors are only now becoming symptomatic –Since the advent of HAART in 1996 Almost 90% drop in mortality

18. Perinatally acquired HIV What we know… Growth (especially height) and sexual development are delayed –Chronic moderate-severe immune suppression –High viral loads  Hilgartner MW, et al. Pediatr. 2001;107(4):59-60  Buchacz K, et al. JAIDS. 2003;33(1):56-65.  Mahoney EM, et al. JAIDS. 1991;21(4):333-337.

19. Perinatally acquired HIV What we know… Neurological effects: –HIV encephalopathy Chronic low grade Fulminant –Cognitive deficits and developmental delays –Hearing loss –Below average IQ

20. Perinatally acquired HIV What we know… Psychiatric disease –Depression –Anxiety –ADHD –Behavioral problems Significantly associated with HIV-infected youth Increases risk of suicidality, psychiatric hospitalization, high-risk sex, drug/alcohol abuse  Futterman DC, et al. Adolesc Med Clin. 2004;15(2):369-391.  Murphy DA, et al. Pediatr. 2004;113(6):544-551.  Gaughan DM, et al. Pediatr. 2004;113(6):544-551.

21. Perinatally acquired HIV What we know… Psychosocial effects: –Almost 75% live without biological parents –More than 75% have been orphaned by their mother –More than 25% are delayed in schooling –About 25% are in special education  Grubman S, et al. Pediatr. 95(5):657-663.

22. What we know… Behavior characteristics of all adolescents 60% of high school graduates are sexually active Oral sex as less risky:20% (9 th grade students) have had oral sex –More than 30% plan on having oral sex  Futterman DC, et al. Adolesc Med Clin. 2004;15(2):369-391  CDC. MMWR. 2004:53(no. SS-2)  Halperin-Felsher BL, et al. Pediatr. 2005;115(4):845-851.

23. What we know… Behavior characteristics of HIV + adolescents 90% are active even after knowing HIV status: 50% use condoms Majority of girls intend to have children  FuttermanDC, et al. Adolesc Med Clin. 2004;15(2):369-391  Ezeanolue EE, et al. J Adolesc Health. 2006;38(6):719-725 At risk for sexually-transmitted infections including HPVcervical cancer

24. What we know… Adolescents are less adherent to HAART and OI prophylaxis  Murphy DA, et al. Arch Pediatr Adolesc Med. 2003;157;249-255  Futterman DC, et al. Adolesc Med Clin. 2004;15(2):369-391. Potential for: – ARV resistance –Transmission of resistant virus Unsafe sex practices

25. What we know… Social stigma –Multigenerational nature of disease –“fitting in” –Denial impedes disclosure to patients Unwitting transmission to peers Medical, psychological, and social problems are vastly connected into one large problem The cycle continues…

27. What we want to know… Research question(s): –What are the medical and psychosocial characteristics of Jackson Memorial Hospital’s perinatally infected adolescent cohort? –What kind of patients are we transferring to adult care? –Recent literature is scarce.

28. Age of cohort in 2005* Age (years) Number of patients * n =166. Mean: 16.4 years; Median: 16.0 years

29. Disclosure By 13 years old: –155 of 166 (93.4%) knew their diagnosis Family or medical team members did the disclosing –11 of 166 (6.6%) were not disclosed 3 were considered competent

30. CDC Classifications From worst ever to 2005 B 2 A 1 N C 3 Number of patients

31. 2005 Cohort* Growth Parameters Percentile Number of patients *n = 166

32. 2005 Growth Parameters Age ≥ 18 years * Percentile Number of patients *n = 44

33. 2005 Growth Parameters Age ≥ 18 years * Percentile Number of patients *n = 44 29.6%

34. 2005 Growth Parameters Age ≥ 18 years * Percentile Number of patients *n = 44 15.9% 18.1% 11% In US: 13.5% ± 3.1% of 15-18 year olds (grade 9-12) have BMI ≥ 95%ile  CDC Youth Risk Behavior Surveillance. MMWR 2004:53.

35. 2005 Medical Characteristics ConditionNumber of patientsDenominatorPercentage Hospitalization3516621.1 Neutropenia Anemia Thrombocytopenia 52 23 13 163 31.9 14.1 8.0 Abnormal lipid profile Lipodystrophy 32 9 78 164 41.0 5.5 HIV nephropathy1715910.7 Cardiomyopathy 3164 1.8 Neurological disease6416638.6 Opportunistic infection4416626.5 Psychiatric illness6616640.1 Hepatitis B, C Co-infection HBV HCV 9 4 5 166 5.4 2.4 3.0 Hepatitis (Non A, B, C)12164 7.3 12 TGs 11 Cholesterol 09 Both

36. 2005 Medical Characteristics ConditionNumber of patientsDenominatorPercentage Hospitalization3516621.1 Neutropenia Anemia Thrombocytopenia 52 23 13 163 31.9 14.1 8.0 Abnormal lipid profile Lipodystrophy 32 9 78 164 41.0 5.5 HIV nephropathy1715910.7 Cardiomyopathy 3164 1.8 Neurological disease6416638.6 Opportunistic infection4416626.5 Psychiatric illness6616640.1 Hepatitis B, C Co-infection HBV HCV 9 4 5 166 5.4 2.4 3.0 Hepatitis (Non A, B, C)12164 7.3 CD4 count < 200 cells/mL; p < 0.05 88% black; 11% hispanic; 1% white

37. 2005 Medical Characteristics ConditionNumber of patientsDenominatorPercentage Hospitalization3516621.1 Neutropenia Anemia Thrombocytopenia 52 23 13 163 31.9 14.1 8.0 Abnormal lipid profile Lipodystrophy 32 9 78 164 41.0 5.5 HIV nephropathy1715910.7 Cardiomyopathy 3164 1.8 Neurological disease6416638.6 Opportunistic infection4416626.5 Psychiatric illness5616633.7 Hepatitis B, C Co-infection HBV HCV 9 4 5 166 5.4 2.4 3.0 Hepatitis (Non A, B, C)12164 7.3

38. 2005 Neurological Disease* Neurological DiseaseNumber of diagnosesPercentage HIV encephalopathy2238.6 Cognitive dysfunction1526.3 Visual problems § 1322.8 Developmental delay1221.1 Mental retardation 814.0 Motor dysfunction 712.3 Hearing loss 610.5 Seizure disorder 5 8.8 Cerebrovascular accident 2 3.5 Other ‡ 712.3 *n = 57 patients § Includes myopia, nystagmus, traumatic eye injury, strabismus, and retinal detachment. ‡ Includes headache/migraine (3), aseptic meningitis(1), cerebral vasculitis (1), microcephaly (1),and craniosynostosis (1).

39. 2005 Opportunistic Infections* Opportunistic InfectionNumber of diagnosesPercentage Candidiasis § 2045.5 HSV ‡ 1125.0 Dermatophyte ¤ 920.5 HPV ¶ 818.2 Varicella zoster virus 511.4 Tuberculosis Δ 2 4.6 Molloscum contagiosum 2 4.6 Cytomegalovirus † 2 4.6 Cryptosporidiosis 1 2.3 * n = 44 patients § Includes oral (13), esophageal (4), and vaginal candidiasis (3). ‡ Includes oral (10), and esophageal herpes (1) virus infections. ¤ Includes skin/hair (8), and nail (1) Tinea spp infections. ¶ STI and non-STI from HPV. Δ Includes active pulmonary (1), and latent (1) infections. † Includes pneumonia (1), and viremia (1).

40. 2005 Psychiatric Disease* Psychiatric DiseaseNumber of diagnosesPercentage ADHD § 28 50.0 Depression25 44.6 Anxiety Disorders10 17.9 Psychosis 2 3.6 Drug abuse 2 3.6 Bipolar disorder 1 1.8 Other ¶ 2 3.6 * n = 56 patients ‡ Includes generalized anxiety (4), post-traumatic stress (3), panic (1), obsessive-compulsive (1), and adjustment disorders (1). § Includes 5 patients with ADHD and disruptive behavior. ¶ Include gender identity issues (1), and autistic spectrum features (1).

41. 2005 Psychosocial situation Family life Caregiver(s)* Number of patientsPercentage Extended family Biological parents Adopted Foster home Self 69 68 16 10 3 41.6 41.0 9.6 6.0 1.8 Parental death § 1 parent 2 parents 50 67 33.6 45.0 Single parent/caregiver home ‡ 9155.5 HIV + biological siblings ¤ 1811.2 Education Current (2005) schooling ¶ 3 20 103 13 2 2.1 14.0 72.0 9.1 1.4 Elementary Middle school High school College Vocational Special Education ‡ 1811.0 Highest education completed Δ 23 103 29 14.8 66.5 18.7 Elementary Middle school High school Employment ‡ 1810.9 *n = 166; § n = 149; ‡ n = 164; ¤n = 161; ¶ n = 144 (3 are not in school); Δ n = 155 patients respectively.

42. 2005 Psychosocial situation Family life Caregiver(s)* Number of patientsPercentage Extended family Biological parents Adopted Foster home Self 69 68 16 10 3 41.6 41.0 9.6 6.0 1.8 Parental death § 1 parent 2 parents 50 67 33.6 45.0 Single parent/caregiver home ‡ 9155.5 HIV + biological siblings ¤ 1811.2 Education Current (2005) schooling ¶ 3 20 103 13 2 2.1 14.0 72.0 9.1 1.4 Elementary Middle school High school College Vocational Special Education ‡ 1811.0 Highest education completed Δ 23 103 29 14.8 66.5 18.7 Elementary Middle school High school Employment ‡ 1810.9 *n = 166; § n = 149; ‡ n = 164; ¤ n = 161; ¶ n = 144 (3 are not in school); Δ n = 155 patients respectively. 59 % 79%

43. Intelligence Quotient* 50 (37.3%) § 28 (20.9%) § 4 (3.0%) § IQ ranges Number of patients * n = 133 patients § Out of 133patients Mean: 78.3; SD ± 15 Median: 79 Range: 47 - 116 3 (2.2%) § 48 (36.1%) § Moderate MR Mild MR Mean IQ white Americans: 101.4; SD ± 15 Mean IQ hispanic Americans: 91 Mean IQ black Americans: 86.9; SD ± 13  Reynolds CR, et al. J School Psychol. 1987;25(4):323-342 Mean IQ white Americans: 89.7; SD ± 11 Mean IQ hispanic Americans: 81.5; SD ± 17 Mean IQ Caribbean black: 79.5; SD ± 14 Mean IQ African Americans: 75.9; SD ± 15

44. 2005 Psychosocial situation Number of patients PercentageDenominator Sexually active Barrier protection Partner disclosure Pregnancy 30 19 11 2 18.1 63.3 36.7 6.7 166 30 Tobacco use 8 4.8 166 Alcohol use* 5 3.0 166 Street drugs Marijuana use § Documented ‡ 7 2 4.2 1.2 166 Trouble with the law ¤ 5 3.0 166 * Reported as occasional alcohol use. § Marijuana was the only street drug reported to be used. ‡ Documented marijuana use by screening test(s). ¤ Includes incarceration for felony third degree: Under Florida law: Not disclosing HIV status to sexual partner(s). 3 had STI: 2 had HPV 1 had HPV & Trichomonas vaginitis

45. Antiretroviral Therapy Total number of patients on therapy: –155 out of 166 (93.4%) –2 of 155 patients on FI 11 patients not on ARV –Not immune suppressed and asymptomatic Did not need ARV –Or stopped ARV on their own.

46. Antiretroviral Resistance Of those with resistance to NRTI (n = 111) All patients with available resistance profiles* (n = 143) NumberPercentageNumberPercentage Resistance to all NRTI No resistance to NRTI 23 N/A 20.7 N/A 23 28 16.1 19.6 Of those with resistance to NNRTI (n = 96) All patients with available resistance profiles* (n = 143) NumberPercentageNumberPercentage Resistance to all NNRTI No resistance to NNRTI 95 N/A 99.0 N/A 95 47 66.4 32.9 Of those with resistance to PI (n = 62) All patients with available resistance profiles* (n = 143) NumberPercentageNumberPercentage Resistance to all PI No resistance to PI 19 N/A 30.7 N/A 19 82 13.3 57.3 Resistance to all NRTI, NNRTI, and PI1409.8 * 12 patients had no resistance testing done because they had undetectable viral loads throughout ARV therapy.

47. Viral load logarithms and CD4 count %ages HIV copies/mLNumber of patientsDenominatorPercentage < 400 400-1000 1001-10 000 10 001-100 000 > 100 000 29 55 29 17 159 18.2 34.6 18.2 10.7 CD4 countsNumber of patientsDenominatorPercentage 0 – 199 200 – 499 ≥ 500 30 56 73 159 18.9 35.2 45.9 CD4 count %agesNumber of patientsDenominatorPercentage < 15 15 - 24 ≥ 25 37 43 82 162 22.8 26.5 50.6 Mean viral load: 3572 copies/mL Mean viral load log: 3.55 ± 0.9 Mean 485 ± 299 Mean 23.5 ± 11

48. Conclusions

49. Conclusions HIV/AIDS in adolescents –Multi-faceted –Multi-generational Overall, our cohort –Immune competent despite ongoing viral replication –Short Many overweight –Multiple medical problems Neurological (HIV encephalopathy) Lipid abnormalities OI were common but not life-threatening (Candida spp, HSV) Psychiatric (ADHD, Depression, Anxiety)

50. Conclusions Most carry HIV with ARV mutations –About 60% have at least to 1 NRTI –About 20% have to all NRTI –About 70% have to all NNRTI –About 60% have none to PI –Almost 10% have to all NRTI, NNRTI, and PI Compliance problems?

51. Conclusions Multiple psychosocial problems –Vast majority are not living with biological parents Single parent homes Orphaned –Below average IQs Almost all are in school with only 11% in special education classes –Minority are employed –Disturbing number Don’t wear condoms Don’t disclose their status to sex partner(s) –Some have gotten into trouble with the law

52. Conclusions At pediatric HIV clinics –Discussion with patients about drugs/alcohol/tobacco –Safe sex practices –Encouraged to abstain from sex until “older” if not sexually experienced Despite this –Many don’t listen We advocate continued discussion of these issues even after transition to “adult” care.

53. Future Work We know that perinatally-infected adolescents have preserved immune status despite viremia Potential questions for discussion: –HAART treatment “interruptions” with only 3TC or FTC monotherapy for selected adolescents? Maintains a low HIV replication capacity Preserves immune status ARV class sparing –Avoids mutation pressure Once daily –Easier regimen –Enhances adherence –Continued psychosocial work to improve ARV adherence.

54. More questions for discussion… Do children treated early with HAART –Experience growth failure? –IQ drop? What kind of HIV-positive adults are we transferring to adult care?

55. Acknowledgements Gwendolyn B. Scott, MD The University of Miami’s Pediatric Infectious Diseases Department Dr. Dorothy L. Moore Dr. Normand Lapointe 