Neurocognitive Development in Perinatally Human Immunodeficiency Virus–infected Adolescents on Long-term Treatment, Compared to Healthy Matched Controls: A Longitudinal Study

Abstract

Background A cross-sectional analysis of the Neurological, cOgnitive and VIsual performance in hiv-infected Children cohort showed significant cognitive impairment in combination antiretroviral therapy (cART)-treated, perinatally human immunodeficiency virus (HIV)-infected adolescents (PHIV+) compared to age-, sex-, ethnicity- and socioeconomic status (SES)-matched HIV-negative controls (HIV−). In this longitudinal study, we compared cognitive development in the same adolescents over time. Methods We repeated the standardized cognitive test battery after a mean of 4.6 years (standard deviation 0.3). In participants who completed both assessments, we compared cognitive trajectories between groups in the domains of intelligence quotient (IQ), processing speed, working memory, executive functioning, learning ability, and visual-motor function, using linear mixed models. We explored associations with disease- and treatment-related factors and used multivariate normative comparison (MNC) to determine the prevalence of cognitive impairment. Results There were 21 PHIV+ and 23 HIV− participants that completed 2 assessments and were similar concerning age, sex, ethnicity, and SES. Compared to HIV− participants, in PHIV+ participants the IQ score increased significantly more over time (group*time 6.01, 95% confidence interval [CI] 1.5–10.50; P = .012), whereas executive functioning decreased significantly more (group*time −1.43 z score, 95% CI −2.12 to −0.75; P < .001), resulting in the disappearance and appearance of significant differences. Processing speed, working memory, learning ability, and visual-motor function trajectories were not statistically different between groups. Univariately, those who had started cART at an older age deviated more in executive functioning (−0.13 z score, 95% CI −0.24 to −0.02; P = .043). The prevalence of cognitive impairments by MNC was similar in both groups, at both time points. Conclusions The cART-treated PHIV+ adolescents appeared to have similar global cognitive development, compared to their healthy peers. Executive functioning trajectory appears to deviate, potentially explained by earlier brain damage.

Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption

“…Poorer intellectual performance in PHIV children compared to adoption matched peers is consistent with previous evidence from the NOVICE cohort using non-adopted control group [3, 11]. Both cross-sectional and longitudinal evidence from the NOVICE cohort, showed poorer intellectual functioning in PHIV children compared to both Dutch norm group and controls matched for age, sex, ethnicity and SES [3, 11]. The persistent finding of lower IQ in PHIV children, also when matching for adoption status, further supports the association between treated HIV and IQ.…”

“…Longitudinal observation of the NOVICE cohort showed similar trajectories in overall cognitive performance over time compared to healthy peers, yet suggested executive dysfunctioning in PHIV children once having reached adolescence[11]. However in this cross-sectional design–with regards to other cognitive domains–our results suggest no differences between groups in the domains of processing speed, working memory, executive function, learning ability and visual motor function.…”

“…Research to date tends to focus on HIV-uninfected (or HIV-exposed but HIV-uninfected) control groups that are matched for age, sex, ethnicity and socioeconomic status (SES), rather than adoption status. Previous results from our NOVICE cohort (neurological, cognitive, and visual performance in perinatally HIV-infected children), indicated poorer cognitive functioning in PHIV compared to controls [3, 11]. However, PHIV children in our cohort were more often adopted compared to the HIV- uninfected control group, this precluding us from investigating any effect of adoption on HIV-associated cognitive impairment.…”

“…We reverse coded variables in order to align interpretation in the same direction: for all tests lower scores indicate poorer test performance. We summarized subtests into the following aggregated domains: intelligence quotient (IQ) working memory, processing speed, learning abilities, executive functioning and visual-motor functioning, based on a principal component analysis (PCA), as described previously [11]. (S1 Table).…”

“…To investigate the association between HIV and cognitive performance we used linear regression models with each cognitive domain as continuous outcome. We adjusted the domains of processing speed, working memory, executive function, learning ability and visual-motor function for IQ in order to prevent possible obscuring of IQ effects on outcomes of other domains [11].…”