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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/mm3 (interquartile range [IQR] 88‐389), and 60% of participants had commenced ARV treatment before advanced disease occurred. Mean CD4 count at enrollment was 464 cells/mm3 (SD 226.3). Seven participants (14%) had a CD4 count <200 cells/mm3. Four (8%) had a pVL >1000 copies/mL; all were on carbamazepine. Three participants with elevated pVL had a CD4 count <200 cells/mm3. None had documented adherence concerns by providers; however, two had events concerning for clinical failure. HIV genotype testing showed mutations in three participants. Carbamazepine was not found to correlate with elevated pVL (P =.58). 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/mm3 and were virally suppressed. Carbamazepine was not associated with an increased risk of virological failure or ARV‐resistant HIV. [ABSTRACT FROM AUTHOR]

Background: Evidence on the association between female-to-male human immunodeficiency virus (HIV) transmission risk and hormonal contraception is sparse and conflicting.Methods: Heterosexual HIV-discordant couples from Lusaka, Zambia, were followed longitudinally at 3 month-intervals from 1994 to 2012. The impact of hormonal contraception on time to HIV transmission from HIV-positive women to their HIV-negative male partners (M-F+) was evaluated.Results: Among 1601 M-F+ couples, 171 genetically linked HIV transmissions occurred in men over 3216 couple-years (5.3 transmissions/100 couple-years; 95% confidence interval [CI], 4.5-6.2). In multivariable Cox models, neither injectable (adjusted hazard ratio [aHR], 0.6; 95% CI, .4-1.2), oral contraceptive pill (aHR, 0.8; 95% CI, .3-2.1), nor implant (aHR, 0.8; 95% CI, .5-1.4) use was associated with HIV transmission, relative to nonhormonal methods, after controlling for the man's age at baseline and time-varying measures of pregnancy, self-reported unprotected sex with the study partner, sperm present on a vaginal swab wet mount, genital inflammation of either partner, genital ulceration of the man, and first follow-up interval. Sensitivity analyses, including marginal structural modeling and controlling for viral load and fertility intentions available in a subset of couples, led to similar conclusions.Conclusions: Our findings suggest null associations between hormonal contraception and risk of female-to-male HIV transmission. We support efforts to increase the contraceptive method mix for all women, regardless of HIV serostatus, along with reinforced condom counseling for HIV-serodiscordant couples. [ABSTRACT FROM AUTHOR]

Background: There are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure., Methods: In this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered., Results: Nineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9)., Conclusions: Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gretchen Birbeck and Izukanji Sikazwe report financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To describe longitudinal outcomes and predictors of cognitive outcomes in children with HIV in Zambia., Background: Multiple studies have shown that children with HIV are at risk for impaired cognition. However, there are limited data on longitudinal cognitive outcomes in children with HIV., Methods: We conducted a prospective cohort study of 208 perinatally infected children with HIV ages 8-17 years, all treated with antiretroviral therapy, and 208 HIV-exposed uninfected controls. Participants were followed for 2 years. Cognition was assessed with a custom NIH Toolbox Cognition Battery, and tests were combined to generate a Summary Cognition Score (SCS). The contribution of potential risk factors to outcomes was explored using regression models and group-based trajectory modeling., Results: HIV was strongly associated with lower SCS at baseline [β-14, 95% confidence interval (CI): -20 to -7, P < 0.001]. Change scores over time were similar between groups, but poorer average performance in children with HIV persisted at the 2-year follow-up visit (adjusted β = -11, 95% CI: -22 to -0.3, P = 0.04). Other than HIV, the strongest predictors of baseline SCS included socioeconomic status index (β =3, 95% CI: 1, 5, P = 0.004), history of growth stunting (β=-14, 95% CI: -23 to -6, P = 0.001), history of CD4 count below 200 (β = -19, 95% CI: -35 to -2, P = 0.02), and history of World Health Organization stage 4 disease (β = -10, 95% CI: -19 to -0.2, P = 0.04). In the group-based trajectory model, HIV+ status predicted membership in the lowest performing trajectory group (odds ratio 2.5, 95% CI: 1.2 to 5.1, P = 0.01)., Conclusions: Children with HIV are at risk of poor cognitive outcomes, despite chronic treatment with antiretroviral therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

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.

Objective: To determine the impact of hormonal contraceptive methods on risk of HIV acquisition among HIV-negative women cohabiting with HIV-positive male partners., Study Design: From 1994-2012, HIV discordant couples recruited from a couples' voluntary HIV counseling and testing center in Lusaka, Zambia were followed longitudinally. HIV-negative partners were tested quarterly. This analysis is restricted to couples in which the man was HIV-positive and the woman was HIV-negative at enrollment and the man was not on antiretroviral treatment. Multivariate Cox models evaluated associations between time-varying contraceptive methods and HIV acquisition among women. Sensitivity analyses explored exposure misclassification and time-varying confounder mediation., Results: Among 1393 couples, 252 incident infections occurred in women over 2842 couple-years (8.9 infections per 100 couple-years; 95% CI, 7.8-10.0). Multivariate Cox models indicated that neither injectable [adjusted hazard ratio (aHR)=1.2; 95% CI, 0.8-1.7], oral contraceptive pill (OCP, aHR=1.3; 95% CI, 0.9-1.8), or implant (aHR=1.1; 95% CI, 0.5-2.2) use was significantly associated with HIV acquisition relative to non-hormonal contraception controlling for woman's age, literacy and time-varying measures of genital ulceration/inflammation. This remained true when only looking at the subset of infections acquired from the spouse (82% of infections) and additionally controlling for baseline HIV viral load of the male partner, pregnancy status, and time-varying measures of sperm on a vaginal swab wet prep and self-reported unprotected sex. OCP and injectable users reported more unprotected sex (p<.001), and OCP users were more likely to have sperm on vaginal swab (p=.1) than nonhormonal method users., Conclusions: We found no association between hormonal contraception and HIV acquisition risk in women. Condom use and reinforced condom counseling should always be recommended for HIV discordant couples. HIV testing of sex partners together is critical to establish HIV risk, ascertain couple fertility intentions and counsel appropriately., Implications: These findings add to a controversial literature and uniquely address several common design and analytic challenges faced by previous studies. After controlling for confounders, we found no association between hormonal contraception and HIV acquisition risk in women. We support promoting condoms for HIV prevention and increasing the contraceptive method mix to decrease unintended pregnancy., (Copyright © 2015 Elsevier Inc. All rights reserved.)