Philippa Musoke MBChB PhD Department of Paediatrics and Child Health

1. Complications of HIV in perinatally infected adolescents and young adults in resource-poor settings PhilippaMusokeMBChB PhD Department of Paediatrics and Child Health College of Health Sciences, School of Medicine MakerereUnversity Kampala Uganda and MUJHU Research Collaboration

2. Outline Complications of HIV infection in adolescents • Malnutrition • Chronic lung disease • Tuberculosis • Lipodystrophy

3. Malnutrition and HIV infection • Most HIV infected children are malnourished • Median wt- and ht-for-age z-score <-2 • In 30 different studies of children on ART (Sutclife) • 30 – 50% of children hospitalized with severe acute malnutrition (SAM) are HIV+ (Bachou H) • Mortality of children with HIV and SAM is 4 times higher than those with SAM alone (30% vs 8%) (Fergusson P) • Severe pneumonia and SAM were risk factors for death in hospitalized children (Preidis GA J Pediatr 2011) Fergusson P, et al Trans R Soc Trop Med Hyg 2008; Sutcliffe et al CG , Bachou H et al. Nutr J 2006,

4. Adolescents physical changes • Stunted and wasted • Dermatological changes • Puberty delayed • Complications from ART

5. STUNTING in HIV infected sibling

6. Severe malnutrition post ART • ARROW trial – Compared children who were hospitalized with SAM ( both edematous and non-edematous types) and those not hospitalized • 39/1207 (3.2%) were hospitalized (20 with edema) • Median days after ART initiation = 27 days • Age median 6 years (3-17 years) • Children with advanced disease n =220 (CD4% & WAZ<-3 SD) • 7.3% (95% CI 3.8–10.7) kwashiorkor (K) • 3.2 % (95% CI 1.2–6.1) marasmus (M) • Mortality at 24 wks - 32% marasmus; 20% kwashiorkor - compared to 1.7 % for non hospitalized children Prendergast A et al AIDS 2011

7. Chronic Lung disease in adolescents • HIV infected ART naïve adolescents • N=116 (Zimbabwe) • Mean Age: 14 years + 2.6 years • 43% male • Chronic cough 66% • >40% had hypoxia at rest • Pathology: small airway disease associated with bronchiectasis Ferrand RA et al CID 2011

8. Increase incidence of Tuberculosis disease in HIV infected children • Cohort of south African children randomized to INH or placebo(548 HIV+ and 804 HIV- infants) (Smith) • 121 TB cases /1000 child-years (CI 95-153) HIV+ • 41 TB cases/1000 child-years (CI 31-52) HIV – • No benefit of INH prophylaxis • IRIS (20-30% of children on ART) • 29% of IRIS events in children were TB –Uganda (Orikiriiza) • 71% % of IRIS events in children were TB –S.Africa (Mahdi)Majority BCG adenitis Mahdi SA et al NEJM 2011; Orikiriiza J et al AIDS 2009; Smith K et al AIDS 2009

9. Prevalence of Immune Reconstitution Syndrome • Cohort of 162 Ugandan children on ART • 38% ( CI 31-36) developed IRIS • Median Age 6 years (IQR 2.5-12 years) • Tuberculosis was the most common event=29% • Others - pruritic papular eruptions (PPE) , candida and pneumonia • Factors associated with IRIS • Male sex OR 2.96 (1.30-6.74) • Pre-ART CD4% OR 4.39 (1.62-11.08) • CD8+ < 1000 cells/ul OR 4.56 (2.01-10.34) • Cough(current) OR 4.30 (1.84-10.08) Orikiriiza J et al AIDS 2010

10. Lipodystrophy in Resource-Limited Settings • Thailand • 90 HIV+ children on ART (NNRTI) • Lipodystrophy – 9%, 47% and 65% at 48, 96 and 144 weeks • 11% dyslipidemia • India • 52 HIV + children ( 25 ART – non PI, 27 not on ART) • Only 4 had cholesterol • 2 lipoatrophy, 3 triglycerides ( follow up 3 months) • Brazil • 30 children (30% on PI) median duration on ART 28 mths • 53% lipodystrophy, 60% dyslipidemia Aurpibul L et al Antivir Ther 2007; Parakh A Indian J Pediatr; Sarni RO et al J Pediatr

11. Lipodystrophy on ART • 364 children enrolled in a cross sectional study, Uganda • Median age was 8 years ( range 2-18) • Prevalence of fat redistribution was 27% • Only 29% of them also had hyperlipidaemia • Prevalence of hyperlipidemia was 34% • Factors associated with fat redistribution Tanner stage >2, age > 5yrs and use of d4T regimen J Int AIDS Soc. 2012

12. THANK YOU