Data |
Annual visits* |
Interim visits+ |
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V1 |
V2 |
V3 |
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Demographics1: Age, sex, grade level, race, tribe, primary language, neighborhood of residence |
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Birth history1: Prematurity, birth weight, birth complications, ARV exposure during pregnancy |
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Developmental screen2: Ten Question Screen |
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Medical history1: History of other significant medical problems |
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HIV infection history1: Clinical and immunologic stage, current and past medications, time on treatment, adherence, history of opportunistic infections |
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Review of socioeconomic status, environment2: Food security, maternal education, wealth |
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Stressful life events2: Questions regarding events which may result in emotional stress |
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Physical exam: Standardized neurologic exam and anthropometry (Height, weight, body mass index, mid-upper arm circumference, head circumference) |
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Zambia Depression Assessment-Pediatric2: Developed during study as detailed above in text |
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Interim history1: Review changes in health state, social status, psychological functioning |
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HIV infection data: CD4 count and %, viral load |
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Biomarker panel: TNF-α, sCD163, sCD14, CRP, IL-6, IFN γ, TNFR1&2 |
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Flow cytometry panel: Characterize of monocyte, platelet, and lymphocyte populations |
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Gold Standard neuropsychological testing: IQ estimate, attention, memory, language, executive function, fine motor speed; developmental milestones evaluation (age 3-6 years only) |
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NIH Toolbox-Cognition Battery3: IQ estimate, attention, memory, language, executive function, fine motor speed |
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NIH Toolbox-Emotion Battery3 |
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Qualitative interview for depression: Subjects rate their understanding of depression symptoms & questionnaire items |
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Neuroimaging: Non-sedated structural brain MRI without contrast - standard clinical sequences, volumetric assessment, DWI, ADC sequences; brain MRA |
[scheduled after V1 for eligible subjects] |
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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 (%) |
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0.3 |
Nyanja |
141 (68%) |
138 (66%) |
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Bemba |
47 (23%) |
45 (22%) |
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English |
1 (<1%) |
7 (3%) |
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Other |
18 (9%) |
19 (9%) |
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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) |
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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 (%) |
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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 (%) |
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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 |
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DKEFS TMT Visual Scanning1 |
Pattern Comparison Processing Speed Test* |
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Oral Symbol Digit test |
Motor Speed |
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DKEFS TMT Motor Speed1 |
Nine Hole Pegboard Dexterity Test |
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Learning / Immediate Recall |
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CVLT-C List A Trials 1-5 Total2 |
Auditory Verbal Learning Test |
UNIT-2 Spatial Memory task3 |
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Executive Function – Inhibit |
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Pencil Tapping Test |
Flanker Inhibitory Control and Attention Test* |
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Executive Function – Set Shifting / Cognitive Flexibility |
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Wisconsin Card Sorting Test |
Dimensional Change Card Sort Test (DCCS) * |
DKEFS TMT Letter-Number Sequencing1 |
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Attention / Working Memory |
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WISC-V Digit Span4 |
List Sorting Working Memory |
CVLT-C Trial 12 |
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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) |
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3-5 |
6-7 |
8-17 |
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Gold Standard Neuropsychological Assessment |
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Letter-Number Screening |
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Malawi Developmental Assessment Test1 |
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Universal Nonverbal Intelligence Test – Second edition |
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Delis Kaplan Executive Function System Trail Making Test2 |
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California Verbal Learning Test for Children |
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Pencil Tapping Test |
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NEPSY-2 Affect Recognition |
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NEPSY-2 Verbal Fluency3 |
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Wisconsin Card Sorting Test |
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WISC-V Digit Span |
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NIH Toolbox Cognition Battery4 |
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Pattern Comparison Processing Speed Test |
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Flanker Inhibitory Control & Attention Test |
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Dimensional Change Card Sort Test |
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9-Hole Pegboard Test |
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4-Meter Walk Gait Speed Test |
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List Sorting Working Memory Test |
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Auditory Verbal Learning Test |
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Oral Symbol Digit Test |
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Mood and Behavior Assessment |
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Patient Health Questionnaire-9, Youth Self Report |
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Patient Health Questionnaire-9, Parent Proxy Report |
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Behavior Rating Inventory of Executive Function – Second edition |
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Brief Impairment Scale |
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NIH Toolbox Emotion Battery4 - Parent Proxy Measures |
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Fear |
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Perceived Stress |
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Sadness |
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Positive Parental Relationship |
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Self-Efficacy |
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Domain Specific Life Satisfaction |
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NIH Toolbox Emotion Battery4 - Self Report Measures |
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Emotional Support |
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Fear |
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Perceived Stress |
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Sadness |
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Maternal Relationships |
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Self-Efficacy |
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General Life Satisfaction |
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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.