Early Initiation of Antiretroviral Therapy is Protective Against Seizures in Children With HIV in Zambia: A Prospective Case–Control Study

Background: Seizures are relatively common among children with HIV in low- and middle-income countries and are associated with significant morbidity and mortality. Early treatment with antiretroviral therapy (ART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy. Methods: We conducted a prospective, unmatched case–control study. We enrolled children with new-onset seizure from University Teaching Hospital in Lusaka, Zambia and 2 regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016 to 2019. Early treatment was defined as initiation of ART before 12 months of age, at a CD4 percentage .15% in children aged 12–60 months or a CD4 count .350 cells/mm³ for children aged 60 months or older. Logistic regression models were used to evaluate the association between potential risk factors and seizures. Results: We identified 73 children with new-onset seizure and compared them with 254 control children with HIV but no seizures. Early treatment with ART was associated with a significant reduction in the odds of seizures [odds ratio (OR) 0.04, 95% confidence interval: 0.02 to 0.09; P, 0.001]. Having an undetectable viral load at the time of enrollment was strongly protective against seizures (OR 0.03, P, 0.001), whereas history of World Health Organization Stage 4 disease (OR 2.2, P = 0.05) or CD4 count, 200 cells/mm³ (OR 3.6, P, 0.001) increased risk of seizures. Conclusions: Early initiation of ART and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV.