Risk of Neurodevelopmental Disorders in Children Exposed to HIV and Antiretrovirals In Utero: A National Cohort Study in France

Abstract

Background: The health of children exposed but uninfected by human immunodeficiency virus (HIV) requires long-term assessment, in particular in terms of neurological and cognitive development. Numerous confounding factors have hampered such assessment, and published data are contradictory.

Methods: Using data from the French National Health Data System from 2012 to 2022, we conducted a population-based matched cohort study on all live-born single children, including those born to mothers with HIV, all prenatally exposed to antiretrovirals (ARVs). The primary outcome was the diagnosis of neurodevelopmental disorders according to the International Classification of Diseases, 10th Revision. The recourse to specialized consultations likely to indirectly reflect neurodevelopmental symptoms was also evaluated. Incidence was assessed using the Cox survival model.

Results: Of 6 667 363 live-born singletons, 9035 were born to mothers with HIV, all exposed to ARVs during pregnancy. Children were followed for up to 11 years (average, 5.5 years). Overall, the incidence of neurodevelopmental disorders among exposed children was higher than in the general population, even after matching for 5 sociodemographic criteria and gestational age (hazard ratio, 1.24 [95% confidence interval, 1.04-1.47]). It was not possible to dissect the respective role of maternal infection from that of maternal treatment, as all children were coexposed to HIV and ARVs. However, among those exposed to tenofovir-emtricitabine, the ritonavir-boosted darunavir-based combination was significantly associated with a higher combined incidence of neurodevelopmental disorders and related specialized consultations than other protease inhibitors (log-rank P < .001).

Conclusions: Children exposed to HIV and ARVs in utero have a higher risk of developing neurodevelopmental disorders of multifactorial origin.

Keywords: HIV; antiretrovirals; children; neurodevelopment; pregnancy.