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

Abstract

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 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 as well as two regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016-2019. Early treatment was defined as initiation of ART prior to 12 months of age, at a CD4 percentage greater than 15% in children ages 12 months to 60 months, or a CD4 count greater than 350 cell/mm3 for children 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 to 254 control children with HIV but no seizures. Early treatment with antiretroviral therapy was associated with a significant reduction in the odds of seizures (OR 0.04, 95% CI 0.02—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), while history of WHO Stage 4 disease (OR 2.2, p=0.05) or CD4 count <200 (OR 3.6, p<0.001) increased risk of seizures. Conclusions: Early initiation of antiretroviral therapy and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV.