Inutero and peripartum antiretroviral exposure as predictor of cognition in 6- to 10-year-old HIV-exposed Ugandan children - a prospective cohort study.

Abstract

To quantify association between in utero/peripartum antiretroviral (IPA) exposure and cognition, i.e. executive function (EF) and socioemotional adjustment (SEA), in school-aged Ugandan children who were perinatally HIV-infected (CPHIV, n=100) and children who were HIV-exposed but uninfected (CHEU, n=101). Children were enrolled at age 6-10years and followed for 12months from March 2017 to December 2018. Caregiver-reported child EF and SEA competencies were assessed using validated questionnaires at baseline, 6 and 12months. IPA type - combination antiretroviral therapy (cART), intrapartum single-dose nevirapine±zidovudine (sdNVP±ZDV), nevirapine+zidovudine+lamivudine (sdNVP+ZDV+3TC) - or no IPA (reference) was verified via medical records. IPA-related standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) in cognitive competencies were estimated from regression models with adjustment for caregiver sociodemographic and contextual factors. Models were fitted separately for CPHIV and CHEU. Among CPHIV children, cART (SMD=-0.82, 95% CI: -1.37 to -0.28) and sdNVP±ZDV (SMD=-0.41, 95% CI: -0.81 to -0.00) vs. no IPA predicted lower executive dysfunction over 12months. Intrapartum sdNVP+ZDV+3TC vs. no IPA predicted executive dysfunction (SMD=0.80, 95% CI: 0.30-1.31), SEA problems (SMD=0.63-0.76, 95% CI: 0.00-1.24) and lower adaptive skills (SMD=-0.36, 95% CI: -0.75-0.02) over 12months among CHEU. Further adjustment for contextual factors attenuated associations, although most remained of moderate clinical importance (|SMD|>0.33). Among CPHIV children, cART and sdNVP±ZDV IPA exposure predicted, on average, lower executive dysfunction 6-10years later. However, peripartum sdNVP+ZDV+3TC predicted executive and SEA dysfunction among CHEU 6-10years later. These data underscore the need for more research into long-term effects of in utero ART to inform development of appropriate interventions so as to mitigate cognitive sequelae.