Neuro developmental outcomes of children with HIV

1. Neuro developmental outcomes of children with HIV Diane Melvin Consultant Clinical Psychologist & Rebecca Biggs Clinical Specialist Paediatric Physiotherapist St Mary’s Hospital Family HIV clinic October 2008

2. Thanks to: Colleagues at St Mary’s Hospital Family HIV Clinic & from wider services But special thanks to all those children and their families who have contributed to our knowledge and provided materials for this presentation

3. Overview • Why monitor neurodevelopment now? • What is known? • How could we monitor? • What to do next?

4. Why monitor outcomes? • Political imperatives: Are services effective? performance of services dictate development of services and funding • Ethical and Professional imperatives: Ensuring services meet patients needs and delivered appropriately, enable clinicians to reflect and improve services for patients • Personal imperatives These youngsters want to know what future holds! And want support to achieve their goals

5. In UK most children with vertically acquired HIV are now staying healthier and getting older Newborn Toddler preschool • The time is right for new outcomes: • to address changing needs in life & future and suggest interventions • to compare group skills and functions with UK child population norms School Aged Teenager Young Adult

6. Recent findings Children with HIV consistently found to have lower mean scores on sensori-motor and cognitive tasks than uninfected controls • Reported incidence of HIV encephalopathy 10-20% (Willen, 2006) • Progressive HIV encephalopathy less common (Mitchell et al, 2001) • CNS damage is not reversible, but does not progress if good viral control. (Jeremy et al, 2005; Lindsey et al, 2007; Shanbhag et al, 2005) • Some compensation or enhanced performance following treatment with improvement in energy, health, nutrition etc. • Higher risk of developmental delay if already infected at birth(McGrath et al, 2006) • Infants with early severe disease more likely to have abnormal neurology than if less symptomatic early disease (Foster et al, 2007)

7. Definitions: Neurodevelopmental Outcomes Definition & Terminology dilemmas e.g. HIV encephalopathy: ‘a failure to attain or loss of developmental milestones or loss of intellectual ability, impaired brain growth, or an acquired microcephaly and an acquired symmetric motor deficit ‘(Center for Disease Control and Prevention (CDC) Pediatric AIDS, 1994) • CNS compromise or neurodevelopmental vulnerability rather than encephalopathy(Willen, 2006)

8. What is appropriate comparison for UK cohort? • What is an appropriate comparison group for UK? • US data - High percentage of maternal intra venous drug misusers • Developing world access to health care different & high levels of poverty & poor nutrition • Premature cohort or other chronic conditions present from birth with known CNS involvement? • What is assessed? • Assessment of global v specific functions • Structural imaging v functional outcomes

9. Neurodevelopmental Consequences: What we’ve learnt? • Vertically acquired HIV is differentto those who acquire HIV later • Triggers differ for • Developmental/functional consequences (background chronic vulnerability) • Neurological signs (an event(s)) • Spectrumof difficulties: none/mild/moderate/severe 1. Developmental/functional consequences: A. Direct (virus effects on developing CNS structures or pathways –complex mechanisms) B. Indirect effects (interaction of factors: constitutional, illness history, psychosocial) UNCLEAR contribution of A and B 2. Neurological consequences: Known cofactors increase risk • Prematurity • maternal IV drug misuse • early childhood infections e.g. CMV ADDITIONAL contribution to 1 (Stins et al, 2004, Canto-Nogues et al, 2005, Schwartz & Major, 2006, Eugenin et al, 2007)

10. Representation of individual or group profiles May reflect change over time Individual may have neurological consequences, but with appropriate intervention (developmental & medicines) expect changes in functional presentation Neurological and developmental consequences Severe developmental /functional problems Severe Neuro No Neuro No developmental /functional problems

11. Common Neurological Presentations Significant: Hypertonia: diplegia > hemiplegia (cerebral palsy picture) Microcephaly Developmental delay or neuro-cognitive impairment (scores >-2sd below mean) Epilepsy (rare in UK) Subtle: Increased tone Poor motor planning/sequencing of movements Broad based gait

12. Common developmental/functional profiles Younger age • Delays in achieving early milestones – speech delays, subtle motor problems • Some – problems with regulation e.g. appetite, sleep/awake, toileting School age • Poor attention and concentration and impulse control (ADD features) • Others with passivity and poor expressive skills (ASD features) • Difficulties in planning and organisation of complex movements (sensori-motor problems) • Better receptive skills than application ones • Underachievement at school

13. Older children/adolescents • Increased reports of problems with new learning and working memory, planning ahead, thinking through consequences, applying self, sustaining effort etc. (‘executive functioning profiles’) • New neurological signs rare (if well controlled virus) • Higher viral load associated with poorer functions including motor speed (Jeremy et al, 2005 , Foster, Harris et al 2008) • Some increase in depression & antisocial behaviours. • School problems and immaturity persist. • Some long term treatment effects e.g. body shape & image • What is just ‘adolescence’? • What is due to increased demands on vulnerable system? • Who decides what is a “quality life”?

14. What are we finding in UK vertically infected populations?

15. Audit of Neurological and Developmental findings in HIV infected children attending the Family Clinic, St Mary’s Hospital(February 2007)

16. Key Findings • 49% have developmental concerns identified e.g by parents, school or Family Clinic multi-disciplinary team. • 19% have demonstrable abnormal neurological signs • Present pre-school children have the highest incidence of abnormal neurological signs (40%) and significant developmental delays (53%) • Present adolescents – low incidence of neurological signs - high incidence functional problems • Of 120 school age children, 49 (40%) receive some additional educational support including School Action Plus/Statements

17. School age children: Cognitive outcomes & Quality of Life • Cognitive: IQ mean within normal limits, slight skew to low average • Attainments (reading & spelling) Over 40% had scores > 2 yrs below their age and ability (IQ) • Parental and child concerns on Pedsqol quality of life scale • Most concerns were ‘mild’ • Most concerns over school functioning – especially forgetfulness, paying attention in class, keeping up with peers School age 9-12 years. N=53 100 = No concerns PEDSQOL RATINGS Krechevsky & Melvin 2008

18. Emotional/behavioural outcomes • Most problems with coping and adjustment not psychiatric disorder • Behavioural presentations – in keeping with attention and executive function deficits • Suggestion of illness fatigue in adolescence (burn out) • Level of reported emotional (depression and anxiety) and behavioural (conduct, over activity) in keeping with other chronic illness populations (14 % Melvin et al 2006) • Causation of ‘depression’? • ‘reduced drive’ (internal) and/or external stressors

19. Summary : Neurodevelopmental outcomes CNS Vulnerability Immature CNS & HIV Chronic vulnerability of CNS increasing susceptibility to acute CNS insult Neurological consequences Known early cofactors increase risk Developmental/functional weaknesses Direct and indirect influences increase CNS VULNERABILITY Differential effects suggest importance of resilience and protective factors As demands increase (e.g. learning) performance less good Common profile of weaknesses Regulation, organisation, sustainability/speed of response, memory application ? Midbrain/prefrontal ‘executive functioning’ ART medicines can Enhance developmental progress Protect but not reverse previous neurological signs

20. Monitoring and Interventions for neurodevelopmental consequences

21. Screen for emotional and behavioural outcomes as well as physical • Screening allows identification of those who need more in depth assessment and/or referral • Repeated screening - child acts as own control • Look for changes in ‘risk and resilience’ factors changes since previous assessment e.g. new carer, treatments www.chiva.org.uk

22. How could paediatric HIV services monitor development? Developmental Monitoring: • Screening ( PHP group developing tool) • Regular e.g. annual review • Integrate screening into clinic visits • Incorporate child development knowledge • Systematic collection of data e.g. school reports, number of referrals to other services, incidence of reported developmental problems, External referral for developmental needs: • What needs to be shared about the HIV diagnosis? “Sometimes, it ends up being just information and maybe that person doesn’t use it for whatever they do. So sometimes you think you may not have made any difference if I hadn’t of told them.” (parent of disabled, HIV infected child, Biggs 2005)

23. Individual changes in functions over time Child S No neuro signs IQ average Family conflict Sec school Poorer adherence No extra help ARV started Extra help Maternal ill health

26. Its never too late for interventions! Normal development informs us: • Development is dynamic = children constantly and actively change • Different CNS processes and functions mature at different times = problems can present differently over time • Early events shape later progress but are not only determinant of existing skills and functions • Brain has ability to develop new pathways and compensate and integrate new influences and experiences (i.e. adolescence) • In general population there is a distribution of abilities • Individual resilience & general protective factors e.g. quality of relationships

27. Outcomes: past, present, future? past present future Severe developmental /functional problems RISK Severe Neuro RESILIENCE No Neuro No developmental /functional problems

28. Clearer definitions e.g. encephalopathy, quality of life? Need UK Outcomes: core screening across centres? Longitudinal follow up? What are appropriate interventions, how to sustain & evaluate effects? Long term medicine effects? Exposed infants? Will there be medicines (ART) with greater efficacy for CNS protection? Still more questions than answers

29. What these children want‘Having as normal a life as possible’ Joining in with friends Achieving relationships having a future