The brain of a child Understanding cognitive development

The brain of a child: Understanding cognitive development for children living with HIV Prof Lorraine Sherr, University College London Member Coalition for Children Affected by AIDS

Presentation AIM • Review the evidence of cognitive impact of HIV for HIV+ve and HIV exposed and Uninfected children • Explore the complexity of responding to cognitive challenges • Community Care study data the role of cash grants, and cash plus care, cash plus nutrition on cognitive outcomes • Chido trial data to show parental factors impact on cognitive outcomes • Examine promising interventions

Cognitive development HIV+ve Children • Systematic reviews • Sherr et al 2009; Sherr et al 2015 • Mc. Henry et al 2018 45 Studies Both HIV+ve and HEU children had worse developmental outcomes compared to HIV Uninfected Unexposed Children. HEU • Cognitive delay • Systematic review – 11 studies (650 HIV affected, 736 Control 205 HIV+ve) Sig lower than controls on at least 1 measure in 7/11 studies. (Sherr et al AIDS Behav 2014, Nov 18(11) 205974); Le Doare et al Pediatrics 2012 Nov 130(5)e 1326 -44 • Morbidity and Mortality effects • Slogrove et al 2016 – 22 studies, 3 specifically designed.

HIV Affected (Filteau et al 2009, Sherr et al AIDS Behav 2014, Nov 18(11) 2059 -74); Le Doare et al Pediatrics 2012 Nov 130(5)e 1326 -44 60 50 40 30 20 10 0 Shapiro Botswana Brahmblatt Uganda Chilongozi Malaawi Sutcliffe Zambia Taha Dev Delay San Cog < av Sanman eechai Beh Msellati Lang 0 Control 20 Exposed 40

33. 8 28. 4 24. 4 20. 3 13. 1 pe tie s 8. 9 di ar in g He Ab no rm al s iff ic ta ld en M ec h es es ul ti ff ic di or ot M 18. 8 10. 3 6. 3 HIV positive non-HIV positive ff ic ul 7. 4 ul ti 40 35 30 25 20 15 10 5 0 An y Percentage HIV +ve children at risk of developmental delay – Community Care Study (Sherr et al various) (n=979) Degree of delay higher among HIV positive children. HIV status remained a strong independent predictor even after adjusting for other confounders (AOR: 4. 55, 95% CI: 2. 29 -9. 04, p<0. 0001)

HIV and other developmental outcomes > emotional and behavioural problems conduct, hyperactivityinattention, or peer problems. � HIV +ve worse at school 60 50 50 Percentage �HIV +ve significantly HIV positive 43. 7 40 32. 3 30 27. 5 25. 5 20 non-HIV positive 14. 1 8. 5 10 3. 7 ar gu l re e At te nd le ss gg l ru St ly s as in ar le ow Sl cl ne la ct c re co r In < health-related quality of life. ss �HIV +ve significantly rs 0 School performance indicators

Percentage of children struggling in school Cash grants and Struggling in school 50% 45% 40% 35% 30% 25% 20% Grant 15% No grant 10% 5% 0% HIV-positive children Non-HIV-positive children Moderation effect of child HIV status on the association between grant receipt and school performance (OR=0. 34; CI=0. 11, 1. 004; p=. 051).

Cash + care and Cognitive ability Sherr Macedo, Tomlinson, Skeen & Cluver BMC 2017 20 Draw-a-person, F(3)=52. 31, p<. 001. 18 130 Digit span F(3)=10. 67, p<. 001 16 120 14 94. 52 Average score 100 90 80 78. 95 97. 71 85. 2 Avergae score 110 12 10 8 7. 81 8. 58 9. 14 Good parenting (n=51) Cash support (n=473) 9. 94 6 70 4 60 2 50 0 40 No support (n=179) Good parenting (n=51) Cash support Cash plus good (n=473) parenting (n=151) No support (n=179) Cash plus good parenting (n=151)

Cash + care and difficulties in remembering (F(3)=3. 99, p=. 008), learning (F(3)=9. 92, p<. 001), and comprehension (F(3)=1. 68, p>. 05) 0. 75 Remembering Learning Avergae score Comprehension 0. 25 No support (n=179) -0. 25 Good parenting (n=51) Cash support (n=473) Cash plus good parenting (n=151)

CASH + NUTRITION controlling for gender, age, HIV status, disability score, no household assets and school attendance Cognitive outcome No Cash Either Cash or good Poor nutrition Nutrition Cash + Good nutrition Cognitive draw a person 1 (Ref) 6. 38 ( 1. 09 -11. 66) * 17. 89 (12. 6123. 17)*** Digit Span 1 (Ref) 0. 84 (-0. 29 - 1. 96) 1. 55 (0. 42 -2. 68)** Learning 1 (Ref) 1. 56 (0. 66 -3. 69) 6. 09 (2. 40 -15. 43)*** Remembering 1 (Ref) 0. 60 (0. 24 -1. 47) 1. 02 (0. 42 -2. 52) Comprehension 1 (Ref) 0. 69 (0. 13 -3. 70) 0. 79 (0. 14 - 4. 52)

COGNITIVE OUTCOMES FOR CASH + NUTRITION 20 No Cash Poor nutrtion 18 16 Either cash or good nutrition 14 12 Cash + Good Nutrition 10 8 6 4 2 0 Draw a Man Cognitive Digit Span Learning Remembering Comprehension

Zimbabwe Chido Trial (Mebrahtu, Chingono, Mupambireyi Ndlovu, Malaba Sherr Cowan et al 2018) Caregiver depression inventory scores and infant cognition Mullen Scales (T-scores) Adjusted coefficient (95% CI) P value* Expressive Language -0. 12 (-0. 26 to 0. 00) 0. 05 Fine Motor -0. 17 (-0. 33 to -0. 01) Gross Motor -0. 10 (-0. 27 to 0. 07) 0. 03 0. 25 Receptive Language -0. 13 (-0. 29 to 0. 02) 0. 09 Visual Reception -0. 26 (-0. 44 to -0. 09) <0. 01 Early Learning Composite Score -0. 32 (-0. 54 to -0. 10) <0. 01 *Adjusted for infant age, HIV status, growth rate, caregiver’s employment status and examiner conducting the Mullen assessments.

Caregiver stress and infant cognition Mullen Scales (T-scores) Adjusted coefficient (95% CI) P value* Expressive Language -0. 06 (-0. 11 to -0. 01) 0. 02 Fine Motor -0. 02 (-0. 09 to 0. 05) 0. 57 Gross Motor -0. 09 (-0. 16 to -0. 03) 0. 01 Receptive Language -0. 06 (-0. 13 to 0. 00) 0. 07 Visual Reception -0. 09 (-0. 16 to -0. 02) 0. 01 Early Learning Composite Score -0. 11 (-0. 20 to -0. 02) 0. 02 *Adjusted for infant age, HIV status, growth rate, and examiner conducting the Mullen assessments.

INTERVENTIONS INTERVENTION STUDY REFERENC EVIDENCE Cognitive rehearsal Boivan et al Good evidence of benefit Stimulation Tomlinson book sharing Walker long term (Jamaica) Good evidence of benefit Parenting Sinovuyo, Cluver et al 2018, ICDP, Incredible years etc… Good evidence of benefit Treat maternal depression Borus Philani trial various Good evidence of benefit Nutrition Neson et al various Good evidence of benefit Community based Support Yakubovich et al, Skeen et all, Thurman et al 2017 Good evidence of benefit ART Various Good evidence of benefit Disclosure Amagugu (Rochat et al 2017) Good evidence of benefit Parental survival ! Good evidence of benefit

CONCLUSION Cognitive challenges exist for some – not all Extends beyond HIV+VE to HEU Time to intervene is overdue Evidence base of efficacy – where is the roll out?

Child Community Care study – Funded by SIDA-NORAD, through Help. Age – Zambia add on funded by Unicef – Supported by Coalition for Children Affected by AIDS

CHIDO TRIAL Prof. Lorraine Sherr Prof. Frances M. Cowan Helen Mebrahtu Dr. Victoria Simms Prof. Helen A. Weiss Rudo Chingono Dr. Zivai Mupambireyi Patience Ndlovu Rickie Mlaba Andrea Rehman