title: Perinatal HIV Status and Executive Function During School-Age and Adolescence: A Comparative Study of Long-Term Cognitive Capacity Among Children From a High HIV Prevalence Setting.
abstract: The aim of this study was to determine whether perinatal HIV infection (PHIV), HIV-exposed uninfected (PHEU) versus HIV-unexposed (PHU) status predicted long-term executive function (EF) deficit in school-aged Ugandan children.Perinatal HIV status was determined by 18 months via DNA polymerase chain reaction test and confirmed at cognitive assessment between 6 and 18 years using HIV rapid-diagnostic test. Primary outcome is child EF measured using behavior-rating inventory of executive function questionnaire across 8 subscales summed to derive the global executive composite (GEC). EF was proxy-reported by caregivers and self-reported by children 11 years or older. Descriptive analyses by perinatal HIV status included derivation of mean, standard deviations (SD), number, and percent (%) of children with EF deficits warranting clinical vigilance. Raw scores were internally standardized by age and sex adjustment. EF scores warranting clinical vigilance were defined as ≥ mean + 1.5SD. t Tests for mean score differences by perinatal HIV status and linear-regression models were implemented in SAS version 9.4 to derive HIV status-related EF deficits (β) and 95% confidence intervals (CIs).Proxy-reported and self-reported EF were assessed in 166 and 82 children, respectively. GEC deficit was highest for PHIV (mean = 121.9, SD = 29.9), intermediate for PHEU (mean = 107.5, SD = 26.8), and lowest for PHU (mean = 103.4, SD = 20.7; P-trend < 0.01). GEC deficit levels warranting clinical vigilance occurred in 9 (15.8%), 5 (9.3%) and 0 (0%) PHIV, PHEU, and PHU children, respectively (P-trend = 0.01). Nineteen percent (n = 32) children had deficits requiring clinical vigilance in ≥2 proxy-reported EF subscales. Of these, multisubscale deficits occurred in 35.1%, 13.0%, and 9.3% of PHIV, PHEU, and PHU respectively (P-trend = 0.001). Multivariable analyses find significantly higher GEC deficits for PHIV compared with PHU and PHEU children regardless of respondent (all P values <0.01). Proxy-reported EF performance was similar for PHEU compared with PHU; however, child self-reported GEC scores were elevated by 12.8 units (95% CI: 5.4-25.5) for PHEU compared with PHU.PHIV had long-term EF deficits compared with other groups. Furthermore, PHEU ≥11 years may have long-term EF deficits compared with PHU, but future studies are needed to clarify this relationship. Cognitive remediation interventions with emphasis on EF may translate to improvements in long-term functional survival in HIV-affected children from sub-Saharan Africa.
authors.affiliation: From the Department of Epidemiology and Biostatistics (AEE, AKN, MZ, MLR, JNS, RK, NK, CCW), the University of Georgia, Athens; Division of Health Protection, Office of HIV, Georgia Department of Public Health (FNK), Atlanta, GA; Directorate of Public Health and Environment (SKZ), Kampala Capital City Authority; and Makerere University College of Health Sciences, School of Public Health (JNS, NK), Kampala, Uganda.
authors.forename: Amara E
authors.initials: AE
authors.lastname: Ezeamama
authors.forename: Florence N
authors.initials: FN
authors.lastname: Kizza
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Zalwango
authors.forename: Allan K
authors.initials: AK
authors.lastname: Nkwata
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Mariana L
authors.initials: ML
authors.lastname: Rivera
authors.forename: Juliet N
authors.initials: JN
authors.lastname: Sekandi
authors.forename: Robert
authors.initials: R
authors.lastname: Kakaire
authors.forename: Noah
authors.initials: N
authors.lastname: Kiwanuka
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Whalen
mesh_terms: D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology*; D003906:Developing Countries; D056344:Executive Function; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000151:congenital* / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D015528:HIV Seroprevalence; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009483:Neuropsychological Tests; D011247:Pregnancy; D012307:Risk Factors; D014454:Uganda