Description: Objective To explore factors associated with HIV virological failure (VF) and HIV drug resistance (HIVDR) among HIV-positive Chinese individuals 4 years after initiating first-line lamivudine-based antiretroviral treatment (ART) in 2008 at five sentinel sites. Design First-line ART initiators who were previously treatment naïve were selected using consecutive ID numbers from the 2008 National Surveillance Database into a prospective cohort study. Questionnaires and blood samples were collected in 2011 and 2012 to assess the outcomes of interest: VF (defined as viral load ≥1000 copies/mL) and HIVDR (defined as VF with genetic drug-resistant mutations). Questionnaires and data from National Surveillance Database assessed demographics and drug adherence data. Results 536 individuals with HIV were analysed; the 4-year risk of VF was 63 (11.8%) and HIVDR was 27 (5.0%). Female participants initiating stavudine (D4T)-based regimens were more susceptible to both VF (adjusted OR (aOR)=2.5, 95% CI 1 to 6.1, p=0.04) and HIVDR (aOR=3.6, 95% CI 1 to 12.6, p=0.05) versus zidovudine-based regimens. Male participants missing doses in past month were more susceptible to both VF (aOR=2.8, 95% CI 1.1 to 7, p=0.03) and HIVDR (aOR=9.7, 95% CI 2.1 to 44.1, p〈0.01). Participants of non-Han nationality were of increased risk for HIVDR (aOR from 4.8 to 12.2, p〈0.05) and non-Han men were at increased risk for VF (aOR=2.9, 95% CI 1.1 to 7.3, p=0.02). All 27 participants detected with HIVDR had non-nucleoside reverse-transcriptase inhibitor mutations, 21 (77.8%) also had nucleoside reverse-transcriptase inhibitor mutations, and no protease inhibitor mutations were detected. Conclusions Our findings suggest successful treatment outcomes at 4 years for roughly 90% of patients. We suggest conducting further study on whether and when to change ART regimen for women initiated with D4T-based regimen, and reinforcing adherence counselling for men. Increased VF and HIVDR risk among non-Han minorities warrants further exploration, and ethnic minorities may be an important group to tailor adherence-focused interventions.

Description: Introduction The association between early exposure to ambient air pollution and adverse pregnancy outcomes in China is unclear. This study will assess the risk of early-life exposure to air pollutants in Beijing and explore the viability of 8-hydroxydeoxyguanosine (8-OHdG) as a biological indicator to assess oxidative stress induced by early-life exposure to air pollution. Methods and analysis Here , 2500 women with singleton pregnancies and their infants will be recruited from the Beijing Obstetrics and Gynecology Hospital. We will collect nine types of biological samples, including maternal serum, urine, placental tissue, umbilical cord tissue and umbilical cord blood during all three trimesters. The air pollution data (particulate matter (PM)2.5, PM10 and similar factors) will be recorded at official fixed-site monitoring stations closest to where the pregnant women live. We plan to assess the effect of air pollutants on adverse pregnancy outcomes and infant respiratory and circulatory disease using Cox regression and competitive risk analysis and explore possible critical windows of exposure during pregnancy using daily pollutant concentrations averaged over various periods of pregnancy combined with individual activity and physiological parameters. Maternal and umbilical cord blood samples (1000 samples) will be randomly selected for 8-OHdG assays to assess the correlation between exposures to air pollutants and oxidative stress. We will determine whether air pollutant exposure or 8-OHdG levels are associated with adverse pregnancy outcomes. SPSS and SAS statistical software will be used for data analysis. Cox regression and competing risk analysis will be used to compute the HR and population attributable risk. Ethics and dissemination This research protocol has already been approved by the Medical Ethics Committee of Beijing Obstetrics and Gynecology Hospital. Written informed consent will be obtained from all study participants prior to enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. Trial registration number This study has been registered in WHO International Clinical Trial Register—Chinese Clinical Trial Registry under registration number ChiCTR-ROC-16010181 ( http :// www.chictr.org.cn / showproj.aspx ?proj=17328 ).

Description: Objective Acute liver failure (ALF) is characterised by overwhelming hepatocyte death and liver inflammation with massive infiltration of myeloid cells in necrotic areas. The mechanisms underlying resolution of acute hepatic inflammation are largely unknown. Here, we aimed to investigate the impact of Mer tyrosine kinase (MerTK) during ALF and also examine how the microenvironmental mediator, secretory leucocyte protease inhibitor (SLPI), governs this response. Design Flow cytometry, immunohistochemistry, confocal imaging and gene expression analyses determined the phenotype, functional/transcriptomic profile and tissue topography of MerTK+ monocytes/macrophages in ALF, healthy and disease controls. The temporal evolution of macrophage MerTK expression and its impact on resolution was examined in APAP-induced acute liver injury using wild-type (WT) and Mer-deficient (Mer –/– ) mice. SLPI effects on hepatic myeloid cells were determined in vitro and in vivo using APAP-treated WT mice. Results We demonstrate a significant expansion of resolution-like MerTK+HLA-DR high cells in circulatory and tissue compartments of patients with ALF. Compared with WT mice which show an increase of MerTK+MHCII high macrophages during the resolution phase in ALF, APAP-treated Mer –/– mice exhibit persistent liver injury and inflammation, characterised by a decreased proportion of resident Kupffer cells and increased number of neutrophils. Both in vitro and in APAP-treated mice, SLPI reprogrammes myeloid cells towards resolution responses through induction of a MerTK+HLA-DR high phenotype which promotes neutrophil apoptosis and their subsequent clearance. Conclusions We identify a hepatoprotective, MerTK+, macrophage phenotype that evolves during the resolution phase following ALF and represents a novel immunotherapeutic target to promote resolution responses following acute liver injury.