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

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 + 1.5(∗)SD. 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.