A brief screening battery for detection of HIV-associated neurocognitive impairment in India

1. A Brief Screening Battery for Detection
of HIV-associated Neurocognitive
Impairment in India
Maiko Sakamoto, Manisha Ghate, Reena Deutsch, Rachel Meyer,
Scott Letendre, Igor Grant, Sanjay Mehendale, Thomas D. Marcotte
HIV Neurobehavioral Research Program, UCSD
National AIDS Research Institute, Pune, India

2. HIV in India
 ~ 2.5 million people living with HIV
» 39% -- female
» 3.5% – children
 Antiretroviral Therapy (ART)
» Free ART at government hospitals in 6 high
prevalence states and the city of Delhi
» Only 7-25% of HIV+ persons have access to
ART
 Mode of Infection
» South – heterosexual contact
» North – IVDUs, prostitution
(from WHO & NACO data)

3. Overall Review of HIV-associated
Neurocognitive Impairment
 Even with ART, the prevalence of HIV-associated neurocognitive
disorders (HAND) is high (~ 50% in the U.S.) (Heaton et al., 2011)
» “Neurocognitive status” is determined based on performance on a
“gold standard” comprehensive NP battery
 The pattern of HAND
» “Spotty” – various cognitive domains are affected by HIV infection
» A challenge in using brief screening measures
70%
60%
50%
40%
30%
20%
10%
0%
Verbal SIP Learning Memory Attn/WM Exec Motor (Heaton et al., 2011)

4. Relationships between HAND and
everyday functions
 Important to detect HAND since it affects not only
cognitive ability but everyday functioning
» Employment and vocational functions (Heaton et al., 2004; Martin et al.,
2006)
» Medication management and adherence (Barclay et al., 2007)
» Driving (Marcotte et al., 2004, 2011)

5. Limitations of the HIV Dementia Scale (HDS)
 HDS – developed in pre-cART era
» The HDS assesses: attention (anti-saccadic errors), memory (4-word
recall), psychomotor speed (written alphabet), construction (cube
copy) (Power et al., 1995)
» Inadequately sensitive to mild HAND
100% 92%
90%
80%
69%
70%
60% 57%
50% Sensitivity
40% Specificity
30% 24%
20%
10%
0%
Raw cutpoint (≤ 10) T-score cutpoint (<40)
(Sakamoto, et al., JAIDS under review)

6. Limitations of the International HIV
Dementia Scale (IHDS)
 IHDS – designed for use with individuals who have limited
literacy (Sacktor et al., 2005)
 The HDS assesses: motor speed (finger tapping), psychomotor
speed (serial hand movements), memory (4-word recall)
» Inadequately sensitive to mild HAND (e.g., Valcour et al., 2011)
Cut-off Value Sensitivity (%) Specificity (%)
11 78 49
10 47 77
9 27 92
8 6 96
(From NeuroAIDS India Study)

7. Aim
 To identify and validate a screening battery, by pairing up
two NP tests, specifically for HIV clinicians in a resource-
limited setting, India.

8. Methods (Participants)
 206 HIV-infected patients from clinics in Pune
 Most of participants were ART naïve
 Exclusion Criteria
» Traumatic brain injury with loss of consciousness greater than 30
minutes
» Non HIV-related neurologic disorders (e.g., epilepsy, Multiple Sclerosis,
etc.)
» Infections that can affect the CNS (e.g., treponema pallidum,
cryptococcus neoformans)
» Current or past psychotic disorder
» Significant substance use
» Color blindness
» Hearing deficit

9. Methods
 Measures:
» “Gold Standard” comprehensive NP battery translated in Marathi
NP Domain NP Test
Learning/Memory Hopkins Verbal Learning Test – Revised
Brief Visuospatial Memory Test - Revised
Executive Function Color Trails 2, Category Test, Stroop – Interference
Wisconsin Card Sorting Test
Verbal Fluency Letter, Animal, Action Fluency
Attention/Working Memory Paced Auditory Serial Addition Test (PASAT)
Spatial Span Test
Motor Grooved Pegboard Test
Speed of Information Processing Digit Symbol Test, Symbol Search Test, Stroop – Color
Trail Making Test – Part A, Color Trails 1

10. Demographic and Medical Characteristics
of India Sample (N = 206)
Variable N, Mean (SD) or Median (IQR)
Age (years) 34.4 (7.26)
Education (years) 9.0 (2.70) (range: 4-17)
Sex (Male) 132 (64%)
AIDS diagnosis 106 (53%)
Plasma viral load (log10 copies/ml) 4.79 (4.01, 5.16)
Current CD4 (cell/mm3) 260 (127, 457)
Current depression 7 (3%)
Substance use disorders (past 12 months) 7 (3%)
NP impaired 68 (33%)

11. Statistical Analysis
 Superiority Index
» Quantifies the performance of each diagnostic test relatives to others and
ranks them by their classification accuracy
Pairwise Comparisons
» “Test X > Test Y” - if sens. & spec. of Test X are better than those of test Y
» “Test X < Test Y” - - if sens. & spec. of Test X are worse than those of test Y
» “Test X = Test Y” – of sens. & spec. of Test X are equal to those of test Y
Superiority Index is a ratio of superior over inferior performance compared to
other tests, accounting for ties
 Recursive partitioning (decision making tree)
» Generates best combinations of tests maximized the balance between the
sensitivity and specificity for NP impairment (Deutsch et al., 2009)

12. Results
 Superiority Index
NP test Rank Superiority Index Sensitivity (%) Specificity (%)
BVMT Learning
1 37.0 55 91
(Learning)
Color Trials 1
2 23.0 43 92
(Proc. Speed)
Grooved Pegboard
3 13.0 39 93
(Non-Dominant) (Motor)
Digit Symbol
4 9.7 49 91
(Proc. Speed)
Category (Executive Fx.) 5 5.0 34 93
Symbol Search
(Proc. Speed) 5 5.0 48 90

13. Results
 Recursive Partitioning
Combination of 2 Tests Sensitivity Specificity Overall
(%) (%) Accuracy (%)
BVMT Learning + Color Trials 1 79 84 83
BVMT Learning + Grooved Pegboard (ND) 74 83 80
BVMT Learning + Digit Symbol 76 83 81

14. Results (Recursive Partitioning)
BVMT Learning
Impaired (n = 49) Normal (n = 157)
NP Impaired Color Trails 1
Normal (n = 12) Normal (n = 130) Impaired (n = 27)
Impaired (n = 37)
NP Normal NP Impaired
Normal (n = 116) Normal (n = 10)
Impaired (n = 14) Impaired (n = 17)
Sens. 79%, Spec. 84%, Overall Accuracy 83%

15. Conclusions
 Best combinations: Visuo-spatial learning (BVMT-R) and
processing speed (Color Trials 1 & Digit Symbol)
 These combinations take 5-10 minutes to administer
 HIV clinicians in India or other international settings may
benefit from using the screening measures described here

16. Limitations
 Selected tests require training to administer, score, and interpret
results
 Copyright issues
 Illiteracy and unfamiliarity with the use of pencils affect
participant’s performance on the IHDS
Ideally, clinicians want a NP screen
» is accurate and yet brief and quick
» requires limited training and minimal staff time

17. Development of an iPad Screening
Battery for HAND
Main goal is to develop an iPad-based screening tool to quickly
assess cognitive functioning in HIV+ individuals
 iPad tests assess:
Learning/Memory
Information Processing Speed
Executive Functioning
Attention/Working Memory
Motor Functioning
 Potential advantages
Need only an iPad
User-friendly, intuitive  administrable in a waiting room
Patients’ performance data will be automatically collected, scored and
summarized

18. Process of the development of iPad
Screening Battery
 Evaluating most sensitive NP tests to HAND
 Assessing test-retest reliability for multiple visits (funding
from the HNRC developmental grant)
 Examining feasibility of the iPad battery at local HIV
clinics
» Collaborations with clinicians
 Developing norms
 Creating international versions of iPad screening battery

19. Summary
Pros Cons
 2 NP tests combinations  Require training to
yield good sensitivity & administer, score, and
specificity interpret results
 Take only 5-10 minutes  Clinicians need to
purchase tests due to
copyrights
HIV Clinicians need a new sensitive NP screen
The iPad battery could be useful for detection of
HAND

20. Thank you