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. 2018 Dec 7;18(1):201.
doi: 10.1186/s12883-018-1205-2.

Mortality & recurrent seizure risk after new-onset seizure in HIV-positive Zambian adults

Melissa A Elafros  1 , Brent A Johnson  2 , Omar K Siddiqi  3   4 , Jason F Okulicz  5 , Izukanji Sikazwe  6 , Christopher M Bositis  7 , Michael J Potchen  8 , Igor J Koralnik  9 , William H Theodore  10 , Lisa Kalungwana  11 , Gretchen L Birbeck  12   13
Affiliations

Mortality & recurrent seizure risk after new-onset seizure in HIV-positive Zambian adults

Melissa A Elafros et al. BMC Neurol. .

Abstract

Background: Recurrent seizure risks in HIV-positive people with new-onset seizure are largely unknown, making it challenging to offer optimal recommendations regarding antiepileptic drug (AED) initiation. Existing outcomes data is limited, and risk factor identification requires a diagnostic assessment, which is often unavailable in regions heavily effected by HIV, like sub-Saharan Africa.

Methods: HIV-positive Zambian adults with new-onset seizure were enrolled in a prospective cohort study to determine seizure recurrence and risk factors for recurrence. Seizure etiology was evaluated, and recurrent seizures and medication usage were assessed during clinic visits. Due to unexpectedly high mortality rates, predictors of death were evaluated using proportional hazards with Gray's test to compare cumulative incidence functions for recurrent seizure across groups adjusting for the competing outcome of death.

Results: 95 patients were enrolled (mean age 37 years, 43% female, 83% with Karnofsky > 50) and followed for a mean of 293 days (median 241 (IQR: 29-532)). At presentation, 50 (53%) were in status epilepticus. The majority (91, 85%) had advanced HIV disease and 65 (68%) were not on combined antiretroviral therapy (cART). After extensive workup, seizure etiology remained unknown in 16 (17%). Average time to cART initiation after enrollment was 61 days. During follow up, 37 (39%) died and 23 (24%) had recurrent seizure. Most deaths (25/37, 68%) occurred in the first 60 days post-index seizure. Individuals with advanced HIV were more likely to die (HR: 19.1 [95% CI: 1.1-333.4]) as were those whose seizure etiology remained unknown (HR: 2.2 [95% CI: 1.1-4.4]). Among participants that survived from enrolment to the end of data collection on 10 May 2013 (n = 58), 20 (34%) experienced recurrent seizures.

Conclusions: New-onset seizure among HIV-positive Zambian adults is associated with high mortality despite good functional status prior to presentation. Advanced HIV infection and failure to identify an underlying seizure etiology are associated with greater mortality. Recurrent seizures occur in over a third of survivors within only 2 years of follow-up. This provides evidence to support AED initiation after first seizure in HIV-positive individuals with advanced HIV disease at the time of presentation though the risks of AED-cART interactions remain a concern and warrant further study.

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Conflict of interest statement

Ethics approval and consent to participate

All participants or their proxies provided written, informed consent to participate. Ethical approval was obtained from the University of Zambia’s Biomedical Research Ethics Committee (UNZA BREC) as well as Michigan State University’s Biomedical Institutional Review Board (MSU BIRB).

Consent for publication

Not applicable.

Competing interests

OKS, IJ, MJP, IJK, and GLB have received funding from the NIH. OKS also received grant funding from the American Academy of Neurology. MJP also received funding from the Dana Foundation. GLB has also played a role in writing guidelines relevant to this patient population. MAE, BAJ, JFO, CMB, WHJ, and LK report no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Mortality after new-onset seizure in HIV+ Zambian adults
Fig. 2
Fig. 2
Mortality after new-onset seizure by etiology among HIV+ Zambian adults
See this image and copyright information in PMC

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