Complications of HIV in perinatally infected adolescents and young adults

in resource-poor settings

Philippa Musoke MBChB PhDDepartment of Paediatrics and Child HealthCollege of Health Sciences, School of MedicineMakerere UnversityKampala UgandaandMUJHU Research Collaboration

Outline

Complications of HIV infection in adolescentso Malnutrition

o Chronic lung disease

o Tuberculosis

o Lipodystrophy

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,

Adolescents physical changes

Stunted and wasted

Dermatological changes

Puberty delayed

Complications from ART

STUNTING in HIV infected sibling

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

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

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

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

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

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

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