Presentation on theme: "Cognitive, neurological and adaptive behaviour functioning among children with perinatally-acquired HIV infection Anita Shet, Smitha Holla, Vijaya Raman,"— Presentation transcript:
1Cognitive, neurological and adaptive behaviour functioning among children with perinatally-acquired HIV infectionAnita Shet, Smitha Holla, Vijaya Raman, Chitra Dinakar, Sapna V, Mysore Ashok St. John’s Medical College Hospital Bangalore, India23-27 July 2012, Washington DC
2BackgroundIncreased 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.We all know thatDrawn our attention to the subtle and not-so-subtle complications of HIV, and one of these includes neurocognitive and behavioral functioning of HIV-infected children.
3Background In infancy: delay in motor and mental development. Drotar D et al. Peds 1997; Chase C et al. Pediatrics 2000.Later childhood: poorer neurocognitive functioning in comparison to HIV-uninfected children.Jeremy RJ, et al. Pediatrics 2005; 380-7Impact of ART: improvement in some test scores.Martin SC, et al. Dev Neuropsychol 2006Other risk factors: malnutrition, poverty, parental illness and death.If we look at some of the accumulated literature on this topic,
4Specific AimsTo 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.To determine whether clinical, immunological, and treatment status can predict adaptive behavior and neurocognitive functioning in HIV-infected children.So we decided to conduct a pilot cross-sectional study to:
5Methods Recruitment sites Inclusion criteria Exclusion criteria ParametersHIV PositiveHIV NegativeRecruitment sitesSt. John’s Hospital pediatric ID clinic;Sneha Care HomeSt. John’s Hospital general pediatric clinic;Prithvi HomeInclusion criteria4-16 yrsRegular HIV care4-16 yearsWell childExclusion criteriaSevere opportunistic infectionsKnown HIV encephalopathy or other neurological diseaseKnown seizure disorder or other neurological disease
6Specific Testing Tools Neurological TestingMotor, sensory, cranial, cerebellar examinations.Soft neurological signs using Physical and Neurological Examination for Soft Signs (PANESS) tool.Cognitive Testing3.5 to 6 yrs: Wechsler Preschool & Primary Scales of Intelligence (WPPSI)7-16 yrs: Wechsler Intelligence Scale for Children, 3rd Ed (WISC-III) (Verbal and Performance IQ)Adaptive BehaviourAbility to adjust to different situations for day-to-day functioning.The Vineland Adaptive Behaviour Scales (VABS) assesses personal and social functioning.
7Results: Patient characteristics ParametersHIV Positive (82)HIV Negative (85)pAge (yrs)8.5 ± 2.78.7 ± 2.80.7Males (%)59 (47, 71)55 (45, 65)Orphans (%)29 (19, 39)38 (29, 49)0.2Annual income ($)8409120.4Parental education (yrs)9100.1Coming to results you can see that the 2 groups were well matched for age (mean age….) gender and orphan status.
9Results: Patient characteristics ParametersHIV Positive (82)HIV Negative (85)Age at diagnosis6.8 ± 3.1-HIV Clinical Stage78% were WHO stage 1 or 2Current CD4 (%)25 (16, 39)Children on ART (%)48%ART Regimen (65%)d4T + 3TC+ NVP
10Soft Neurological signs PANESS ScoreHIV Positive (82)HIV Negative (85)pTotal Score7.5 (3, 13)4 (2, 10)0.02Age 4-6 yrs16 (12, 20)16 (8, 21)0.8Age 7-10 yrs5.5 (3, 9)3 (1, 5)0.008Age ≥ 11 yrs3 (1, 6)2 (1, 5)0.3Boys8.5 (5, 16)5 (2, 10)0.03Girls5 (2, 13)4 (1, 10)0.4HIV-infected children had higher scoresDifference most marked at ages 7-10 yrs.Boys with HIV had more abnormal soft neurological signs.
11Cognition: IQ Scores IQ Score HIV Positive (82) HIV Negative (85) p Total IQ Score75 ± 1388 ± 15< 0.001IQ Verbal78 ± 1490 ± 17IQ Performance76 ± 1387 ± 15HIV-infected children had lower IQ scores compared to HIV-uninfected children, irrespective of age, sex, orphan status, anemia status
12Adaptive behaviour (VAB) VAB ScoreHIV Positive (82)HIV Negative (85)pTotal score94 ± 1095 ± 130.6AgensMales vs FemalesOrphans96 ± 989 ± 100.008Non-orphans99 ± 130.01The results were a little more complicated when we looked at the scores with respect to orphan status: among the non-orphans -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.
13IQ Scores: ART status Score Total IQ p=0.006p=0.06p=0.02Not on ART (39)On ART (43)ScoreThen we focused on only the children who were HIV positive. As expected, use of ART (represented by the green bars) was associated with significantly higher total IQ scores, and performance IQ scores, with a trend seen in verbal IQ scores, when compared to those children not on ART (as seen in the orange bars). Suggesting that ART has a role in improving overall cognitive functioning.Total IQPerformance IQVerbal IQART may have a role in improving overall cognitive functioning
14IQ Scores in children not on ART AgeIQ Score (SD)p4 – 6 years78.0 (11.7)7 – 10 years77.1 (11.3)>10 years75.7 (17.3)0.01When we looked more closely at the children who were not on ART, we found that mean total IQ scores demonstrated a tendency to decrease with increasing age. These decreases are relatively small – but does this indicate subtle worsening of the cognitive impairment among those children who seem to be clinically doing well, but not on ART – with possible uncontrolled viral replication occuring?Among children who were not on ART, mean total IQ scores demonstrated a tendency to decrease with increasing age
15IQ Scores and VABS: Immunological status CD4 ≥ 15%78Low CD4 (<15%)96IQ Score69VABS score89We also found that immunological status appeared to influence cognitive and behavioral functioning. Clearly those children with higher Cd4 levels (>15%) – seen in the blue - had higher IQ scores compared to those with low CD4 levels – seen in yellow bars. And a similar finding among the VABS scores.Total IQ ScoreVABS
16Multivariate regression analysis CognitionIndependent 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 signsHIV status had no independent effect
17ConclusionsHIV-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.
18Recommendations Routine neurocognitive assessments in children Early initiation of ARTEarly intervention and stimulation, with focus on educational and emotional development
19Acknowledgements St. John’s Research Society for funding support National AIDS Control OrganizationSneha Care Home and Prithvi House staffStaff at the ID and general pediatric clinicsChildren and caregivers who participated