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Anita Shet, Smitha Holla, Vijaya Raman, Chitra Dinakar, Sapna V, Mysore Ashok St. John’s Medical College Hospital Bangalore, India Cognitive, neurological.

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Presentation on theme: "Anita Shet, Smitha Holla, Vijaya Raman, Chitra Dinakar, Sapna V, Mysore Ashok St. John’s Medical College Hospital Bangalore, India Cognitive, neurological."— Presentation transcript:

1 Anita Shet, Smitha Holla, Vijaya Raman, Chitra Dinakar, Sapna V, Mysore Ashok St. John’s Medical College Hospital Bangalore, India Cognitive, neurological and adaptive behaviour functioning among children with perinatally-acquired HIV infection July 2012, Washington DC

2 Background Increased access to ART for children will result in improved survival. HIV is now a chronic disease. Neurocognitive and behavioral functioning of HIV-infected children: an important area to address.

3 Background In infancy: delay in motor and mental development. –Drotar D et al. Peds 1997; Chase C et al. Pediatrics Later childhood: poorer neurocognitive functioning in comparison to HIV-uninfected children. –Jeremy RJ, et al. Pediatrics 2005; Impact of ART: improvement in some test scores. –Martin SC, et al. Dev Neuropsychol 2006 Other risk factors: malnutrition, poverty, parental illness and death.

4 Specific Aims 1.To examine the effects of HIV infection on cognitive, neurological, and behavioral functioning on children by comparing these areas in HIV-infected and HIV-uninfected children. 2.To determine whether clinical, immunological, and treatment status can predict adaptive behavior and neurocognitive functioning in HIV-infected children.

5 Methods ParametersHIV PositiveHIV Negative Recruitment sites St. John’s Hospital pediatric ID clinic; Sneha Care Home St. John’s Hospital general pediatric clinic; Prithvi Home Inclusion criteria 4-16 yrs Regular HIV care 4-16 years Well child Exclusion criteria Severe opportunistic infections Known HIV encephalopathy or other neurological disease Known seizure disorder or other neurological disease

6 Specific Testing Tools Neurological Testing  Motor, sensory, cranial, cerebellar examinations.  Soft neurological signs using Physical and Neurological Examination for Soft Signs (PANESS) tool. Cognitive Testing  3.5 to 6 yrs: Wechsler Preschool & Primary Scales of Intelligence (WPPSI)  7-16 yrs: Wechsler Intelligence Scale for Children, 3 rd Ed (WISC-III) (Verbal and Performance IQ) Adaptive Behaviour  Ability to adjust to different situations for day-to-day functioning.  The Vineland Adaptive Behaviour Scales (VABS) assesses personal and social functioning.

7 Results: Patient characteristics Parameters HIV Positive (82) HIV Negative (85) p Age (yrs)8.5 ± ± Males (%)59 (47, 71)55 (45, 65)0.7 Orphans (%)29 (19, 39)38 (29, 49)0.2 Annual income ($) Parental education (yrs)9100.1

8 Results: Patient characteristics Parameters HIV Positive (82) HIV Negative (85) p Age (yrs)8.5 ± ± Males (%)59 (47, 71)55 (45, 65)0.7 Orphans (%)29 (19, 39)38 (29, 49)0.2 Annual income ($) Parental education (yrs) Underweight (%)71 (62, 82)36 (26, 46) < * Stunted (%)83 (75, 91)28 (17, 37) < * Anemia (%)39 (28, 52)23 (13, 33) 0.02 *

9 Results: Patient characteristics ParametersHIV Positive (82) HIV Negative (85) Age at diagnosis6.8 ± 3.1- HIV Clinical Stage 78% were WHO stage 1 or 2 - Current CD4 (%)25 (16, 39)- Children on ART (%)48%- ART Regimen (65%)d4T + 3TC+ NVP-

10 Soft Neurological signs PANESS Score HIV Positive (82) HIV Negative (85) p Total Score7.5 (3, 13)4 (2, 10)0.02 Age 4-6 yrs16 (12, 20)16 (8, 21)0.8 Age 7-10 yrs5.5 (3, 9)3 (1, 5)0.008 Age ≥ 11 yrs3 (1, 6)2 (1, 5)0.3 Boys8.5 (5, 16)5 (2, 10)0.03 Girls5 (2, 13)4 (1, 10)0.4  HIV-infected children had higher scores  Difference most marked at ages 7-10 yrs.  Boys with HIV had more abnormal soft neurological signs.

11 Cognition: IQ Scores IQ Score HIV Positive (82) HIV Negative (85) p Total IQ Score75 ± 1388 ± 15< IQ Verbal78 ± 1490 ± 17< IQ Performance76 ± 1387 ± 15<  HIV-infected children had lower IQ scores compared to HIV-uninfected children, irrespective of age, sex, orphan status, anemia status

12 Adaptive behaviour (VAB) VAB Score HIV Positive (82) HIV Negative (85) p Total score94 ± 1095 ± Agens Males vs Femalesns Orphans96 ± 989 ± Non-orphans94 ± 1099 ±  Adaptive behaviour scores were similar for both HIV-infected and uninfected children – at all ages, and both in males and females.  Among the orphans HIV-infected children had higher/better scores than orphans without HIV.

13 IQ Scores: ART status Not on ART (39) On ART (43) Total IQ Performance IQ Verbal IQ p=0.02 p=0.006 p=0.06 Score ART may have a role in improving overall cognitive functioning

14 IQ Scores in children not on ART Age IQ Score (SD) p 4 – 6 years78.0 (11.7) 7 – 10 years77.1 (11.3) >10 years75.7 (17.3) 0.01  Among children who were not on ART, mean total IQ scores demonstrated a tendency to decrease with increasing age

15 IQ Scores and VABS: Immunological status CD4 ≥ 15% Low CD4 (<15%) Total IQ Score IQ Score VABS VABS score

16 Multivariate regression analysis Cognition Independent factors that affected IQ scores: HIV status (OR 9.1) Weight-for-age Z score (OR 2.5) Hemoglobin (OR 2.1) Adaptive behaviour and soft neurological signs HIV status had no independent effect

17 Conclusions HIV-infected children had higher risk of having abnormal soft neurological signs. and lower IQ scores compared to HIV-uninfected children, irrespective of age, gender, orphan status, anemia status. –indicating subtle neurocognitive impairment that may be related to perinatal HIV infection. Malnutrition and anemia had a definite role in poor cognitive outcomes. Use of ART has a positive effect, and subtle worsening may be seen among those children not on ART.

18 Recommendations Routine neurocognitive assessments in children Early initiation of ART Early intervention and stimulation, with focus on educational and emotional development

19 Acknowledgements St. John’s Research Society for funding support National AIDS Control Organization Sneha Care Home and Prithvi House staff Staff at the ID and general pediatric clinics Children and caregivers who participated


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