V4 region of the HIV-1 envelope gene mediates immune escape and may not promote the development of broadly neutralizing antibodies

To date, inducing the production of broadly neutralizing antibodies (bnAbs) against HIV-1 in humans has been unsuccessful. Several studies have explored the coevolution of HIV-1 and neutralizing antibodies (nAbs), but little is known about what affects the lack of bnAbs after long-term infection. A better understanding of the coevolution of the virus and nAbs in cases involving no bnAb production will help in the design of an effective HIV-1 vaccine. An individual with acute CRF01_AE HIV-1 infection who lacked bnAbs at just over 2 years post-infection (p.i.) was identified from a cohort of HIV negative men who have sex with men. The coevolution of the viral envelope gene and nAbs was studied over 741 days p.i. Strain-specific antibodies (ss-Abs) to the transmitted/founder (T/F) virus developed within 54 days p.i., but plasma collected at subsequent time points could not neutralize synchronous viruses until 557 days p.i., when the plasma acquired low-level synchronous but not heterologous neutralizing activity. The V4 region of envelope gene mutated firstly and continually evolve up to 2 years p.i. Multiple variations in the V4 region, including substitutions, deletions and glycosylation mutations, were driven by ss-Abs and mediated immune escape partially by impacting the binding of nAbs to the virus. The remarkable variations in the V4 region mediated immune escape from ss-Abs and contributed to the affinity maturation of ss-Abs against the T/F virus but may not promote the development of bnAbs. Thus, the V4 region might not be a good target for an HIV-1 vaccine.     

Interest in Long-Acting Injectable PrEP in a Cohort of Men Who have Sex with Men in China

Long-acting injectable (LAI) formulations of antiretrovirals (ARVs) as pre-exposure prophylaxis (PrEP) could be an attractive alternative for men who have sex with men (MSM) who are interested in ARV-based biomedical prevention but will not use a daily pill. This study investigated interest in LAI-PrEP in a cohort of MSM in China and characterized how MSM willing to use only injectable PrEP differed from MSM who would use PrEP regardless of modality or not at all. Demographic, behavioral, and risk perception measures were collected and associations investigated. A licensed LAI-PrEP agent would increase the proportion interested in PrEP by 24.5% over oral PrEP alone. Combining interest in oral and injectable PrEP, 78.5% of the sample could be covered if reported interest in PrEP translated into actual uptake. Partnership factors differentiated those who would be willing to use only LAI-PrEP versus any PrEP modality, while higher self-perception of risk was associated with interest in LAI-PrEP versus no PrEP. The addition of a second PrEP modality could yield increased population coverage of PrEP. Social and behavioral research should be undertaken in parallel with clinical development of injectable PrEP agents to identify characteristics of those who are not interested in oral PrEP but would take advantage of ARV-based prevention with the introduction of an injectable product.     

Accelerated onset of chronic wasting disease in elk (Cervus canadensis) vaccinated with a PrPSc-specific vaccine and housed in a prion contaminated environment

Chronic wasting disease (CWD) is a fatal prion disease affecting multiple cervid species. Effective management tools for this disease, particularly in free-ranging populations, are currently limited. We evaluated a novel CWD vaccine in elk (Cervus canadensis) naturally exposed to CWD through a prion-contaminated environment. The vaccine targets a YYR disease-specific epitope to induce antibody responses specific to the misfolded (PrP^Sc) conformation. Female elk calves (n = 41) were captured from western Wyoming and transported to the Thorne-Williams Wildlife Research Center where CWD has been documented since 1979. Elk were held in contaminated pens for 14 to 20 days before being alternately assigned to either a vaccine (n = 21) or control group (n = 20). Vaccinated animals initially received two vaccinations approximately 42 days apart and annual vaccinations thereafter. Vaccination induced elevated YYR-specific antibody titers in all animals. Elk were genotyped for the prion protein gene at codon 132, monitored for clinical signs of CWD through daily observation, for disease status through periodic biopsy of rrectoanal mucosa-associated lympoid tissue (RAMALT), and monitored for YYR-specific serum antibody titres. Mean survival of vaccinated elk with the 132MM genotype (n = 15) was significantly shorter (800 days) than unvaccinated elk (n = 13) of the same genotype (1062 days; p = 0.003). Mean days until positive RAMALT biopsy for 132MM vaccinated elk (6 7 8) were significantly shorter than unvaccinated 132MM elk (990; p = 0.012). There was, however, no significant difference in survival between vaccinated (n = 4) and control (n = 5) elk with the 132ML genotype (p = 0.35) or in timing of positive RAMALT biopsies of 132ML elk (p = 0.66). There was no strong (p = 0.17) correlation between YYR-specific antibody titers and survival time. Determining the mechanism by which this vaccine accelerates onset of CWD will be important to direct further CWD vaccine research.     

Consumption of takeaway meals and risk markers for coronary heart disease,type 2 diabetes,and obesity in children aged 9–10 years: a cross-sectional study

BackgroundFrequent consumption of takeaway meals is associated with increased risks of coronary heart disease, type 2 diabetes, and obesity in adults, but little is known about such risks in childhood. This study aimed to assess whether consumption of takeaway meals is linked to chronic disease in childhood.MethodsA cross-sectional study of UK schoolchildren aged 9–10 years (Year 5) was carried out in a sample of 85 primary schools in London, Birmingham, and Leicester, with a high prevalence of ethnic minority pupils (black African-Caribbean or South Asian). All children in Year 5 classes were invited to participate. Children self-reported their frequency of consumption of takeaway meals, completed a 24 h dietary recall, had anthropometric measurements taken, and provided a fasting blood sample. Analyses were done with multilevel linear modelling allowing for clustering at school level. Ethics approval was obtained and written informed consent secured for all participants.FindingsAmong 3679 invited children, 2529 participated (69% response rate), of whom 1948 (77%) had complete data (1023 girls, 52%). They included similar numbers of children of white European (n=475), black African-Caribbean (496), South Asian (495), and other ethnic origins (482); 499 (26%) never or hardly ever consumed a takeaway meal, 894 (46%) did so less than once per week, and 555 (28%) once or more per week. In analyses adjusted for age, sex, month, school, ethnic group, and socioeconomic status, children who reported eating a takeaway meal once or more per week had higher mean total cholesterol and LDL cholesterol, by 0·09 mmoL/L (95% CI 0·01–0·18) and by 0·10 mmoL/L (0·02–0·18), respectively, than did children who never or hardly ever ate a takeaway meal; their mean fat mass index was also higher (by 5·06%, 95% CI 0·53–9·79). Mean total cholesterol, LDL cholesterol, and fat mass index in the never or hardly ever group were 4·44 mmoL/L, 2·58 mmoL/L, and 2·01 kg/m⁵, respectively. Children who reported more frequent consumption of takeaway meals had substantially higher intakes of energy, fat (percent of energy), and saturated fat (percent of energy), and lower starch, protein, and micronutrient intakes.InterpretationFrequent consumption of takeaway meals in childhood is common and is associated with higher intakes of saturated fat and higher concentrations of LDL cholesterol. This research adds to growing evidence of the adverse health effects of takeaway meals.FundingThis research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (South London) and by grants from Diabetes UK and the Wellcome Trust.     

近10年亲密伴侣暴力国际研究热点的文献计量学分析

目的 从文献计量的角度系统地分析世界各国近10年有关亲密伴侣暴力(intimate partner violence,IPV)的研究热点问题的分布及变化趋势,旨在为我国开展相关研究提供参考依据。方法 检索PubMed数据库2005-2014年收录的相关文献采用书目信息共现挖掘系统(BICOMS)进行文献计量分析,并利用SPSS 20.0软件绘制系统聚类关系图及χ²检验分析热点变化趋势。结果 统计分析表明,国际上在IPV领域发布的科研论文共3 257篇,数量上整体呈上升态势,尤以近3年更为明显。近10年相关研究主题词主要集中在4各方面:IPV的相关损害及疾病、流行病学调查方法、社会支持、IPV及所引起的疾病预防干预知识及措施。分析结果显示,相对前5年,近5年发表的文献侧重于IPV与HIV感染关系的研究(2.0% vs. 1.0%,χ²=4.471,P=0.034),并将研究对象拓展到孕产妇(1.2% vs. 0.4%,χ²=4.805,P=0.028)等人群。结论 近10年IPV领域的研究总体围绕4个方面,近5年的研究热点开始转向其与HIV感染,目标人群开始拓展到普通女性以外其他人群,中国在该领域的研究还处于起步阶段,期待有所突破的研究。     

HIV Incidence and Care Linkage among MSM First-Time-Testers in Shenyang,China 2012–2014

HIV testing is the first step to the fulfillment of Treat as Prevention (TasP) and reaching the 90-90-90 goal in HIV control. However, there are still a large number of Men who have Sex with Men (MSM) have never been tested for HIV before, and little is known about the HIV incidence and care linkage among this population. A Mixed method was used to recruit MSM who had never tested for HIV before from January 2012 to December 2014 in Shenyang, China. Potential MSM participants were invited to attend the enrollment for HIV and syphilis testing at a general hospital-based voluntary counseling and test (VCT). HIV confirmed positive subjects were further tested by BED HIV-1 capture enzyme immunoassay (BED-CEIA) to determine the HIV incidence. Syphilis was screened by the rapid plasma reagent test (RPR) and confirmed by Treponema pallidum particle assay (TPPA). All the HIV positive subjects were referred to the local Center for Disease Control and Prevention (CDC) and clinics for HIV primary care and follow-ups. In total 646 HIV first-time-testers of MSM (FMSM) attended this study, 73.4% (474/646) were aged under 31-year-old and 57.3% (370/646) and used the Internet as their major cruising avenue for seeking male sexual partners. The average prevalence of HIV and current syphilis infection was 10.8% (70/646) and 11.0% (71/646), respectively. The HIV incidence was 10.3 (95% confidence interval [CI] 6.1–14.5)/100PY. Multivariate logistic analysis showed that factors such as use of the Internet as the major cruising avenue (adjusted OR [AOR] 2.7, 95% CI 0.9–7.6) and having a current syphilis infection (AOR 4.2, 95% CI 1.8–12.2) were independent correlates of a recent HIV infection. Of the 95 HIV screening test positive FMSM, 73.7% (70/95) returned and be confirmed positive, 92.9% (65/70) of confirmed patients were linked to care. Among those retained and underwent CD4+ T cell test, 76.3% (42/55) started HIV antiretroviral therapy. Among the unconfirmed, 84.0% (21/25) were non-local migrants. The HIV incidence of FMSM in Shenyang was high. Future HIV testing program needs to keep on expanding among the MSM who have never been tested for HIV yet. The Internet-based campaigns and syphilis testing and treatment could represent an opportunity to get access to this hard-to-reach population and link them to HIV care. Future linkage to HIV care of this population should underscore the usage of HIV rapid diagnostic tests to prevent lost at early steps of linkage.