PrEP Use and Correlates of Use Among a Large, Urban Sample of Men and Transgender Persons Who Have Sex with Men.

We examined recent pre-exposure prophylaxis (PrEP) use (past 6 months) and its correlates among a large sample of men who have sex with men and transgender and gender non-conforming persons participating in a home HIV self-testing program conducted by the New York City Health Department between 11/2016 and 1/2017. Correlates examined included demographic characteristics and HIV-related behaviors in the past 6 months. Associations with recent PrEP use were assessed using log-binomial regression. 400 (22.5%) of 1776 participants reported recent PrEP use. In adjusted models, recent PrEP use was associated with Manhattan residence [adjusted prevalence ratio (aPR) 1.26; 95% confidence interval (CI) (1.04, 1.53)], higher income [aPR 1.29; 95% CI (1.03, 1.62)], and having insurance [aPR 1.89; 95% CI (1.33, 2.69)]. All HIV-related behaviors, except for injection drug use, were individually associated with PrEP use. More research is needed to better understand barriers to PrEP use among patients who are low income and/or uninsured as this may help improve current public health efforts to increase PrEP uptake among disproportionately impacted populations.

Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy.

OBJECTIVE: Somatic variants are a recognized cause of epilepsy-associated focal malformations of cortical development (MCD). We hypothesized that somatic variants may underlie a wider range of focal epilepsy, including nonlesional focal epilepsy (NLFE). Through genetic analysis of brain tissue, we evaluated the role of somatic variation in focal epilepsy with and without MCD. METHODS: We identified somatic variants through high-depth exome and ultra-high-depth candidate gene sequencing of DNA from epilepsy surgery specimens and leukocytes from 18 individuals with NLFE and 38 with focal MCD. RESULTS: We observed somatic variants in 5 cases in SLC35A2, a gene associated with glycosylation defects and rare X-linked epileptic encephalopathies. Nonsynonymous variants in SLC35A2 were detected in resected brain, and absent from leukocytes, in 3 of 18 individuals (17%) with NLFE, 1 female and 2 males, with variant allele frequencies (VAFs) in brain-derived DNA of 2 to 14%. Pathologic evaluation revealed focal cortical dysplasia type Ia (FCD1a) in 2 of the 3 NLFE cases. In the MCD cohort, nonsynonymous variants in SCL35A2 were detected in the brains of 2 males with intractable epilepsy, developmental delay, and magnetic resonance imaging suggesting FCD, with VAFs of 19 to 53%; Evidence for FCD was not observed in either brain tissue specimen. INTERPRETATION: We report somatic variants in SLC35A2 as an explanation for a substantial fraction of NLFE, a largely unexplained condition, as well as focal MCD, previously shown to result from somatic mutation but until now only in PI3K-AKT-mTOR pathway genes. Collectively, our findings suggest a larger role than previously recognized for glycosylation defects in the intractable epilepsies. Ann Neurol 2018.