Test for HIV-associated cognitive impairment in India

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A brief screening battery for detection of HIV-associated neurocognitive …

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

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  • 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 MarathiNP Domain NP TestLearning/Memory Hopkins Verbal Learning Test – Revised Brief Visuospatial Memory Test - RevisedExecutive Function Color Trails 2, Category Test, Stroop – Interference Wisconsin Card Sorting TestVerbal Fluency Letter, Animal, Action FluencyAttention/Working Memory Paced Auditory Serial Addition Test (PASAT) Spatial Span TestMotor Grooved Pegboard TestSpeed 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 IndexNP 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 93Symbol Search(Proc. Speed) 5 5.0 48 90
  • 13. Results  Recursive PartitioningCombination of 2 Tests Sensitivity Specificity Overall (%) (%) Accuracy (%)BVMT Learning + Color Trials 1 79 84 83BVMT Learning + Grooved Pegboard (ND) 74 83 80BVMT Learning + Digit Symbol 76 83 81
  • 14. Results (Recursive Partitioning) BVMT LearningImpaired (n = 49) Normal (n = 157) NP Impaired Color Trails 1Normal (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 HANDMain 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. SummaryPros 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 ofHAND
  • 20. Thank you