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

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.