Prevalence and transmission dynamics of HIV-1 transmitted drug resistance in a southeastern cohort

Background. Transmitted drug resistance (TDR) compromises clinical management and outcomes. Transmitted drug resistance surveillance and identification of growing transmission clusters are needed in the Southeast, the epicenter of the US HIV epidemic. Our study investigated prevalence and transmission dynamics in North Carolina. Methods. We analyzed surveillance drug resistance mutations (SDRMs) using partial pol sequences from patients presenting to 2 large HIV outpatient clinics from 1997 to 2014. Transmitted drug resistance prevalence was defined as =1 SDRMs among antiretroviral therapy (ART)-naïve patients. Binomial regression was used to characterize prevalence by calendar year, drug class, and demographic and clinical factors. We assessed the transmission networks of patients with TDR with maximum likelihood trees and Bayesian methods including background pol sequences (n = 15 246). Results. Among 1658 patients with pretherapy resistance testing, =1 SDRMs was identified in 199 patients, with an aggregate TDR prevalence of 12% (95% confidence interval, 10% to 14%) increasing over time (P =.02). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs; 8%) was common, followed by nucleoside reverse transcriptase inhibitors (4%) and protease inhibitors (2%). Factors associated with TDR were being a man reporting sex with men, white race, young age, higher CD4 cell count, and being a member of a transmission cluster. Transmitted drug resistance was identified in 106 clusters ranging from 2 to 26 members. Cluster resistance was primarily NNRTI and dominated by ART-naïve patients or those with unknown ART initiation. Conclusions. Moderate TDR prevalence persists in North Carolina, predominantly driven by NNRTI resistance. Most TDR cases were identified in transmission clusters, signifying multiple local transmission networks and TDR circulation among ARTnaïve persons. Transmitted drug resistance surveillance can detect transmission networks and identify patients for enhanced services to promote early treatment

Prevalence of hepatitis coinfection and substance use among antiretroviral therapy clinic clients with hazardous alcohol use in Vietnam.

The confluence of injection drug use (IDU), alcohol consumption, and viral hepatitis increases morbidity among persons living with HIV (PWH). We present a secondary analysis of a randomized controlled trial of alcohol reduction interventions in Thai Nguyen, Vietnam conducted between 2016-2018. We assessed hepatitis B (HBV) and hepatitis C (HCV) coinfection among PWH reporting hazardous alcohol consumption and examined differences in IDU and alcohol use by coinfection status. Participants were ≥18 years old, living with HIV, and reported hazardous alcohol consumption per the WHO Alcohol Use Disorders Identification Test Consumption (AUDIT-C; score ≥4 for men, score ≥3 for women). At enrollment, participants were tested for hepatitis coinfection with HBV surface antigen tests and rapid serological HCV tests. Demographic information, IDU, and recent alcohol consumption were assessed via behavioral survey and 30-day timeline follow back. Fishers Exact and Kruskal-Wallis tests were used for statistical testing. Hepatitis coinfection was common among the 440 enrolled PWH: HCV: n = 355 (81%); HBV: n = 5 (1%); HBV and HCV: n = 37 (8%). Only 10% (n = 43) of participants had no hepatitis coinfection. Among those who tested positive for HBV, 36% had previously been diagnosed with HBV; among those who tested seropositive for HCV, 18% had previously received an HCV diagnosis. History of IDU was higher among those with hepatitis coinfection (HBV or HCV coinfection: 88%; HBV and HCV coinfections: 97%) than those without hepatitis coinfection (7%; p<0.01). Median days of alcohol consumption in the last 30 days was higher among those with coinfection (HBV or HCV coinfection: 20 (Interquartile Range (IQR): 10-30); HBV and HCV coinfections: 22 (IQR: 13-28) than those without hepatitis coinfection (10; IQR: 6-21; p<0.01). The syndemic conditions of HIV, hepatitis, IDU, and alcohol use are deeply entangled and challenging to parse out. Integrated health services are warranted to reduce the risk of liver-related morbidity

Keratinocytes as Depository of Ammonium-Inducible Glutamine Synthetase: Age- and Anatomy-Dependent Distribution in Human and Rat Skin

In inner organs, glutamine contributes to proliferation, detoxification and establishment of a mechanical barrier, i.e., functions essential for skin, as well. However, the age-dependent and regional peculiarities of distribution of glutamine synthetase (GS), an enzyme responsible for generation of glutamine, and factors regulating its enzymatic activity in mammalian skin remain undisclosed. To explore this, GS localization was investigated using immunohistochemistry and double-labeling of young and adult human and rat skin sections as well as skin cells in culture. In human and rat skin GS was almost completely co-localized with astrocyte-specific proteins (e.g. GFAP). While GS staining was pronounced in all layers of the epidermis of young human skin, staining was reduced and more differentiated among different layers with age. In stratum basale and in stratum spinosum GS was co-localized with the adherens junction component ß-catenin. Inhibition of, glycogen synthase kinase 3β in cultured keratinocytes and HaCaT cells, however, did not support a direct role of ß-catenin in regulation of GS. Enzymatic and reverse transcriptase polymerase chain reaction studies revealed an unusual mode of regulation of this enzyme in keratinocytes, i.e., GS activity, but not expression, was enhanced about 8–10 fold when the cells were exposed to ammonium ions. Prominent posttranscriptional up-regulation of GS activity in keratinocytes by ammonium ions in conjunction with widespread distribution of GS immunoreactivity throughout the epidermis allows considering the skin as a large reservoir of latent GS. Such a depository of glutamine-generating enzyme seems essential for continuous renewal of epidermal permeability barrier and during pathological processes accompanied by hyperammonemia