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

A E Ezeamama; S K Zalwango; A Sikorskii; R Tuke; P M Musoke; B Giordani; M J Boivin

doi:10.1111/hiv.13094

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

HIV Med. 2021 Aug;22(7):592-604. doi: 10.1111/hiv.13094. Epub 2021 Apr 16.

Authors

A E Ezeamama¹, S K Zalwango², A Sikorskii¹, R Tuke¹, P M Musoke^{3

4}, B Giordani⁵, M J Boivin^{6

7}

Affiliations

¹ Department of Psychiatry, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
² Directorate of Public Health and Environment, Kampala Capital City Authority, Kampala, Uganda.
³ Department of Paediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
⁴ Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
⁵ Departments of Psychiatry, Neurology, and Psychology, University of Michigan, Ann Arbor, MI, USA.
⁶ Departments of Psychiatry and Neurology & Ophthamology, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
⁷ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.

Abstract

Objectives: 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).

Methods: Children were enrolled at age 6-10 years and followed for 12 months from March 2017 to December 2018. Caregiver-reported child EF and SEA competencies were assessed using validated questionnaires at baseline, 6 and 12 months. 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.

Results: 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 12 months. 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 12 months among CHEU. Further adjustment for contextual factors attenuated associations, although most remained of moderate clinical importance (|SMD| > 0.33).

Conclusions: Among CPHIV children, cART and sdNVP ± ZDV IPA exposure predicted, on average, lower executive dysfunction 6-10 years later. However, peripartum sdNVP + ZDV + 3TC predicted executive and SEA dysfunction among CHEU 6-10 years 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.

Keywords: HIV-exposed children; cognitive function; executive function; in utero ART; maternal ART; socioemotional adjustment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents* / therapeutic use
Child
Cognition
Female
HIV Infections* / drug therapy
Humans
Infectious Disease Transmission, Vertical
Lamivudine / therapeutic use
Peripartum Period
Pregnancy
Pregnancy Complications, Infectious* / drug therapy
Prospective Studies
Uganda
Zidovudine / therapeutic use

Substances

Anti-HIV Agents
Lamivudine
Zidovudine

Grants and funding

R21 HD088169/HD/NICHD NIH HHS/United States