Early Antiretroviral Therapy Is Protective Against Epilepsy in Children With Human Immunodeficiency Virus Infection in Botswana

Abstract

Background Seizures are common among patients with HIV/AIDS in the developing world and are associated with significant morbidity and mortality. Early treatment with combination antiretroviral therapy (cART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy. Methods A case-control study of new onset epilepsy among children age 0-18 years with perinatally acquired HIV/AIDS followed in Gaborone, Botswana during the period 2003-2009 was conducted. Children with epilepsy were identified and compared to age-and-sex-matched controls without epilepsy with respect to timing of cART initiation. Early treatment was defined as treatment with cART before the age of twelve months, at a CD4% of greater than 25 in children age 1-5, or at an absolute CD4 count of >350 cell/mm3 in children age 5 and older. Results We identified 29 cases of new onset epilepsy and 58 age and sex-matched controls. The most common identified etiologies for epilepsy were CNS infections and direct HIV neurotoxicity. Only 8 (28%) of the children who developed epilepsy received early treatment compared with 31 (53%) controls (OR 0.36, 95% CI 0.14-0.92, p=0.03). This effect was primarily driven by differences in rates of epilepsy among children who initiated treatment with cART between the ages of 1-5 years (11% vs. 53%, OR 0.11, 95% CI 0.01-1.1, p=0.06). Conclusions Earlier initiation of cART may be protective against epilepsy in children with HIV.

Seizures in Children with HIV infection in South Africa: A retrospective case control study

“…Despite the limitations, this study provides needed and important data on the epidemiology and management of seizures in HIV-infected children. Our results which investigated seizures in HIV-infected children within the Southern African area can be compared to Bearden et al [28]'s previous work with a Botswanan cohort of HIV-infected children. In their study the authors were specifically interested in whether early ART treatment could prevent the onset of epilepsy in these children.…”

Pediatric Cerebral Palsy in Botswana: Etiology, Outcomes, and Comorbidities

“…Our study demographics are similar to what has been reported in prior studies of children in Gaborone. 29 However, compared with the overall population in Botswana, our study population was more urban, had higher levels of education, and had higher levels of literacy.…”

Global Health: Pediatric Neurology

“…17,18 And as previously noted, certain infections such as HIV and malaria have known comorbidities with neurodevelopment, with recognition and early initiation of therapies potentially beneficial in these cases. 19 Furthermore, it is known that malnutrition plays a role in neurodevelopment, with nutritional disorders putting this population further at risk. 20,21 Thus, recognition of associated etiologies with common neurodevelopmental disorders in the developing world provides options for low-resource interventions with potential high impact.…”

“…23,41,48,59 Drug interactions between older ASDs and antimicrobials (such as antiretroviral drugs) are a major concern, as there are generally no enzyme-neutral drugs readily available in most LMICs. 19,60 An analysis of the availability, price, and affordability of ASDs conducted in 46 countries showed suboptimal availability and affordability of ASDs acted as a barrier to treatment. 27 In addition, pediatric formulations are largely unavailable in most developing countries, making dosing more challenging.…”

“…11,60,79 Pediatric HIV infection may affect any part of the nervous system, though effects vary by treatment status. 19,60 In children who are treated with combination antiretroviral therapy (cART), the most common neurologic manifestations are mild cognitive impairment and peripheral neuropathy. 11 In untreated children, however, more than 50% develop HIV-associated progressive encephalopathy, and CNS opportunistic infections are common.…”