Data

Annual

visits*

Interim

visits+

V1

V2

V3

Demographics1: Age, sex, grade level, race, tribe, primary

language, neighborhood of residence

l

 

 

 

Birth history1: Prematurity, birth weight, birth complications, ARV

exposure during pregnancy

l

 

 

 

Developmental screen2: Ten Question Screen

l

 

 

 

Medical history1: History of other significant medical problems

l

 

 

 

HIV infection history1: Clinical and immunologic stage, current

and past medications, time on treatment, adherence, history of opportunistic infections

l

 

 

 

Review of socioeconomic status, environment2: Food security,

maternal education, wealth

l

 

 

 

Stressful life events2: Questions regarding events which may result

in emotional stress

l

l

l

l

Physical exam: Standardized neurologic exam and anthropometry (Height, weight, body mass index, mid-upper arm circumference,

head circumference)

l

l

l

 

Zambia Depression Assessment-Pediatric2: Developed during study

as detailed above in text

 

l

l

 

Interim history1: Review changes in health state, social status,

psychological functioning

 

l

l

l

HIV infection data: CD4 count and %, viral load

l

l

l

 

Biomarker panel: TNF-α, sCD163, sCD14, CRP, IL-6, IFN γ,

TNFR1&2

l

l

l

 

Flow cytometry panel: Characterize of monocyte, platelet, and

lymphocyte populations

 

l

l

 

Gold Standard neuropsychological testing: IQ estimate, attention,

memory, language, executive function, fine motor speed; developmental milestones evaluation (age 3-6 years only)

l

l

l

 

NIH Toolbox-Cognition Battery3: IQ estimate, attention, memory,

language, executive function, fine motor speed

l

l

l

l

NIH Toolbox-Emotion Battery3

l

l

l

l

Qualitative interview for depression: Subjects rate their

understanding of depression symptoms & questionnaire items

l

l

l

 

Neuroimaging: Non-sedated structural brain MRI without contrast - standard clinical sequences, volumetric assessment, DWI, ADC

sequences; brain MRA

[scheduled after V1 for eligible subjects]

Table 1. HANDZ Study Visits - Schedule of Activities

1Interview and/or record review; 2Questionnaire; 3Abbreviated NIHTB completed at interim visits
*annual visits = annual visits are split into two sessions, scheduled approximately 2 weeks apart
+interim visits = occur quarterly, except when annual visits will occur – i.e., at months 3, 6, 9, 15, 18, 21, 27, 30, 33.

Variable

HEU (n=208)

HIV+ (n=208)

P Value

Age

12.5 (2.9)

12.3 (2.4)

0.36

Sex (% male)

48%

55%

0.15

Residence in Lusaka, n (%)

207 (100%)

198 (95%)

0.02

Primary Language, n (%)

 

 

0.3

Nyanja

141 (68%)

138 (66%)

 

Bemba

47 (23%)

45 (22%)

 

English

1 (<1%)

7 (3%)

 

Other

18 (9%)

19 (9%)

 

Primary caretaker non-parent, n (%)

3 (1%)

22 (11%)

0.002

Mother deceased, n (%)

0

18 (9%)

<0.001

Father deceased, n (%)

59 (28%)

55 (26%)

0.64

Attending school, n (%)

177 (85%)

193 (93%)

0.02

Socioeconomic Status, Mean (SD)

 

 

 

Years of Maternal education

6.4 (3.5)

7.6 (3.4)

<0.001

Years of Paternal Education

9.6 (2.5)

10.3 (2.6)

0.005

Monthly income (in kwacha)

1648 (1109)

3079 (1950)

<0.001

Running water in home, n (%)

57 (27%)

100 (48%)

<0.001

Electricity in home, n (%)

154 (74%)

164 (79%)

0.41

Past Medical History, n (%)

 

 

 

Previously hospitalized

55 (26%)

172 (83%)

<0.001

History of TB

0

70 (33%)

<0.001

History of malaria

92 (34%)

131 (63%)

<0.001

Nutritional Status, n (%)

 

 

 

History of malnutrition

9 (4%)

64 (31%)

<0.001

History of Severe malnutrition

5 (2%)

44 (21%)

<0.001

Weight %

29 (26)

16 (18)

<0.001

Height %

30 (28)

15 (18)

<0.001

Head circumference %

60 (28)

56 (28)

0.12

Table 2a. Baseline characteristics for HIV-infected (HIV; cases) and HIV-exposed uninfected (HEU, controls) subjects (N= 416)

Variable

HIV-Infected (Cases)

Undetectable viral load

172 (83%)

Last measured viral load

0 (0-120)

% Adherence over last month

94% (90-100%)

Age (in years) for ART initiation

5.15 (3.7)

Years on ART

7.48 (3.67)

Current CD4 Count

772 (348)

Current CD4 %

31 (10)

Lowest recorded CD4 count

580 (322)

Lowest recorded CD4 %

25 (19)

Current WHO Stage (n in stage 1/2/3/4)

192 / 2 / 5 / 0

Worst WHO Stage (n in Stage 1/2/3/4)

26 / 29 / 52 / 92

Table 2b. Health characteristics of the HIV-infected group (N = 208)

All Values are Mean (SD), Median (IQR), or n (%))

Gold Standard

Neuropsychological Assessment

Test

NIHTB-CB Test

Processing Speed

 

DKEFS TMT Visual Scanning1

Pattern Comparison Processing Speed Test*

 

Oral Symbol Digit test

Motor Speed

 

DKEFS TMT Motor Speed1

Nine Hole Pegboard Dexterity Test

 

 

Learning / Immediate Recall

 

CVLT-C List A Trials 1-5 Total2

Auditory Verbal Learning Test

UNIT-2 Spatial Memory task3

 

 

 

Executive Function – Inhibit

 

Pencil Tapping Test

Flanker Inhibitory Control and Attention Test*

 

Executive Function – Set Shifting / Cognitive Flexibility

Wisconsin Card Sorting Test

Dimensional Change Card Sort Test (DCCS) *

DKEFS TMT Letter-Number Sequencing1

 

 

 

Attention / Working Memory

 

WISC-V Digit Span4

List Sorting Working Memory

CVLT-C Trial 12

 

Table 3. Validation of the NIH Toolbox Cognitive Battery

1Delis-Kaplan Executive Function System – Trail Making Test
2California Verbal Learning Test for Children
3Universal Nonverbal Intelligence Test
4Wechsler Intelligence Scale for Children – Fifth Edition
*Also presented at interim (quarterly) check-in study visits)

Measure

Age (years)

3-5

6-7

8-17

Gold Standard Neuropsychological Assessment

 

 

 

Letter-Number Screening

 

l

l

Malawi Developmental Assessment Test1

l

l

 

Universal Nonverbal Intelligence Test – Second edition

 

l

l

Delis Kaplan Executive Function System Trail Making Test2

 

l

l

California Verbal Learning Test for Children

 

 

l

Pencil Tapping Test

 

l

l

NEPSY-2 Affect Recognition

 

l

l

NEPSY-2 Verbal Fluency3

 

l

l

Wisconsin Card Sorting Test

 

 

l

WISC-V Digit Span

 

l

l

NIH Toolbox Cognition Battery4

 

 

 

Pattern Comparison Processing Speed Test

 

l

l

Flanker Inhibitory Control & Attention Test

 

l

l

Dimensional Change Card Sort Test

 

l

l

9-Hole Pegboard Test

 

l

l

4-Meter Walk Gait Speed Test

 

l

l

List Sorting Working Memory Test

 

 

l

Auditory Verbal Learning Test

 

 

l

Oral Symbol Digit Test

 

 

l

Mood and Behavior Assessment

 

 

 

Patient Health Questionnaire-9, Youth Self Report

 

 

l

Patient Health Questionnaire-9, Parent Proxy Report

 

l

l

Behavior Rating Inventory of Executive Function – Second edition

 

l

l

Brief Impairment Scale

 

 

l

NIH Toolbox Emotion Battery4 - Parent Proxy Measures

 

 

 

Fear

 

l

l

Perceived Stress

 

l

l

Sadness

 

l

l

Positive Parental Relationship

 

l

l

Self-Efficacy

 

l

l

Domain Specific Life Satisfaction

 

l

l

NIH Toolbox Emotion Battery4 - Self Report Measures

 

 

 

Emotional Support

 

 

l

Fear

 

 

l

Perceived Stress

 

 

l

Sadness

 

 

l

Maternal Relationships

 

 

l

Self-Efficacy

 

 

l

General Life Satisfaction

 

 

l

Table 4. HANDZ Neuropsychological Assessment Battery, Mood/Behavior Assessment, and NIH Toolbox Cognitive and Emotion Batteries

1Administered to children ages 3-6 years old only;
2Condition 1 (Visual Scanning) and Condition 5 (Motor Speed) only are presented to children age 6-7 years old; all task conditions are presented to children >8 years old (i.e., also including Condition 2: Number Sequencing; Condition 3: Letter Sequencing; Condition 4: Number-Letter Sequencing)
3Semantic categories only (not "First Letter")
4Cognition Battery and Emotion Battery task versions selected based on subject age. The 4-Meter Gait Speed task is not age-validated for younger subjects but a raw score (time to complete task) is generated and used in our analyses.