Clinical characteristics and outcomes after new‐onset seizure among Zambian children with HIV during the antiretroviral therapy era

Abstract

Objective This study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new‐onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30‐day mortality and cause of death are also reported. Methods Children living with HIV (CLWHIV) with new‐onset seizures were prospectively evaluated at one large urban teaching hospital and two non‐urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed. Results From April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2‐10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non‐accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty‐two (30%) children died within 30 days of the index seizure. Significance Despite widespread ART roll out in Zambia, new‐onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

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

“…However, newonset seizures in children with HIV continues to be a relatively common concern. 5,17 In a previous study conducted in Botswana from 2003 to 2009, we noted that early treatment with ART was protective against epilepsy. 23 We and others have noted that the primary risk factors for seizures in children with HIV included severe immunosuppression leading to opportunistic infections and HIV encephalopathy.…”

“…[7][8][9][10][11][12][13][14][15][16] Treatment of seizures is particularly challenging in populations with HIV in sub-Saharan Africa, given difficulties accessing diagnostic tests and antiseizure drugs and potential drug interactions between antiretroviral therapy (ART) and anti-seizure medications. 17 The widespread introduction of ART has transformed the HIV pandemic in low-and middle-income countries, with severe immunosuppression becoming much less common. [18][19][20][21][22] In areas with access to ART, HIV has been transformed into a chronic, potentially manageable illness.…”

“…23 We and others have noted that the primary risk factors for seizures in children with HIV included severe immunosuppression leading to opportunistic infections and HIV encephalopathy. 5,17,23,24 However, risk factors for seizures in the current era of widely available ART are unclear.…”

Cerebrospinal fluid viral escape can provide clues for the management of HIV-associated neurologic complications: Highlights from the 2023 American Academy of Neurology Annual Meeting, Boston

“…A decade later, despite a high proportion of patients having received ARTs for at least 1 year, HIV-associated seizures remained highly prevalent in the Zambian population. This was likely a consequence of the inconsistent adherence to medications, as illustrated by the advanced HIV stages and low CD4 þ cell counts reported in the later studies [2,3].…”

“…Seizures may also be triggered by tenofovir-associated uremia or by medications administered to treat OIs, such as isoniazid. However, in endemic regions such as Zambia, OIs, most commonly cryptococcal meningitis, remain a prominent cause of newonset seizures in PWH who have inadequate viral suppression [2,3].…”