Browsing by Author "Gelbard HA"

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Early Initiation of Antiretroviral Therapy is Protective Against Seizures in Children With HIV in Zambia: A Prospective Case-Control Study.
(2024-Mar-01) Bearden DR; Mwanza-Kabaghe S; Bositis CM; Dallah I; Johnson BA; Siddiqi OK; Elafros MA; Gelbard HA; Okulicz JF; Kalungwana L; Musonda N; Theodore WH; Mwenechanya M; Mathews M; Sikazwe IT; Birbeck GL; Greater Lawrence Family Health Center, Lawrence, MA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Neurology, University of Michigan, Ann Arbor, MI.; University of Rochester, Center for Health and Technology, Rochester, NY.; Department of Biostatistics, University of Rochester, Rochester, NY.; Department of Psychology, University of Zambia, Lusaka, Zambia.; University of Zambia School of Medicine, Lusaka, Zambia.; University of Zambia, University Teaching Hospitals, Lusaka, Zambia.; San Antonio Military Medical Center, Infectious Diseases Service, HIV Medical Evaluation Unit, San Antonio, TX.; Department of Neurology, University of Rochester, Rochester, NY.; Department of Educational Psychology, University of Zambia, Lusaka, Zambia.; Epilepsy Division, US National Institute of Health, Bethesda, MD; and.; Department of Neurology, Beth Israel Deaconess Medical Center, Global Neurology Program, Boston, MA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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/mm 3 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/mm 3 (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.
Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia.
(2020-Dec) Navis A; Dallah I; Mabeta C; Musukuma K; Siddiqi OK; Bositis CM; Koralnik IJ; Gelbard HA; Theodore WH; Okulicz JF; Johnson BA; Sikazwe I; Bearden DR; Birbeck GL; Department of Biostatistics, Center for AIDS Research, University of Rochester, Rochester, NY, USA.; National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.; Department of Neurology, University of Rochester, Rochester, NY, USA.; Department of Internal Medicine, Center for Vaccines and Virology Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.; University Teaching Hospitals Children's Hospital, Lusaka, Zambia.; Infectious Disease Service, Brooke Army Medical Center, Joint Base San Antonio-Ft Sam Houston, Houston, TX, USA.; Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia.; Greater Lawrence Family Health Center, Lawrence, MA, USA.; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Departments of Neurology, Pediatrics, Neuroscience and Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Chikankata Epilepsy Care Team, Mazabuka, Zambia.
OBJECTIVE: Interactions between enzyme-inducing anti-seizure medications (EI-ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co-usage of ARVs and EI-ASMs is associated with ARV-resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia. METHODS: Eligible participants were ≥18 years of age and concurrently taking ASMs and ARVs for at least 1 month of the prior 6-month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000 copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI-ASM was associated with pVL >1000/mL copies. RESULTS: Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6 months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6 months. Median CD4 nadir was 205 cells/mm SIGNIFICANCE: EI-ASMs are commonly used in sub-Saharan Africa. Despite concurrent use of EI-ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm
Long-term outcomes after new onset seizure in children living with HIV: A cohort study.
(2024-Apr) Birbeck GL; Mwenechanya M; Ume-Ezeoke I; Mathews M; Bositis CM; Kalungwana L; Bearden D; Elafros M; Gelbard HA; Theodore WH; Koralnik IJ; Okulicz JF; Johnson BA; Musonda N; Siddiqi OK; Potchen MJ; Sikazwe I; Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.; University Teaching Hospitals Neurology Research Office, Lusaka, Zambia.; Department of Biostatistics, University of Rochester, Rochester, New York, USA.; Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.; Department of Neurology, University of Rochester, Rochester, New York, USA.; Department of Medicine, San Antonio Military Medical Center, San Antonio, Texas, USA.; Department of Psychology, University of Zambia, Lusaka, Zambia.; Zambian College of Medicine and Surgery, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Clinical Epilepsy Section, US National Institute of Health, Bethesda, Maryland, USA.; Department of Imaging Sciences, University of Rochester, Rochester, New York, USA.; University Teaching Hospitals Children's Hospital, Lusaka, Zambia.; Chikankata Epilepsy Care Team, Mazabuka, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Family and Community Medicine, University of California San Francisco, San Francisco, California, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. METHODS: Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. RESULTS: Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. SIGNIFICANCE: Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. PLAIN LANGUAGE SUMMARY: This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.