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.     

Disparity of human immunodeficiency virus incidence and drug resistance in college student,non-student youth and older men who have sex with men: a cross-sectional study from seven major cities of China

Background:Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM.Methods:We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, <25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance.Results:Overall, 4,496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1,094 NSYM, and 2,837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100PY, 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100PY, and TDR prevalence were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age< 21-year-old, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (AOR: 2.5; 95% CI: 1.0–5.8).Conclusions:College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.     

视网膜光凝术联合中药治疗糖尿病性视网膜病变

目的:探讨口服滋阴凉血散瘀汤联合激光治疗糖尿病性视网膜病变的临床疗效。方法:采用口服滋阴凉血散瘀汤联合视网膜光凝治疗糖尿病性视网膜病变患者,以单纯视网膜光凝为对照组,对比两组患者在治疗后1,6,12mo的视力、视野及新生血管的变化情况。结果:口服滋阴凉血散瘀汤联合光凝治疗组患者12mo时视力提高(62.3%vs43.1%,P=0.037),视野改变(17.0±3.7vs14.9±3.7,P=0.002)及新生血管退缩情况(67.2%vs48.3%,P=0.036)均优于对照组患者。结论:滋阴凉血散瘀汤联合激光治疗糖尿病性视网膜病变较单纯激光治疗更有效。     

Rapid Disease Progression in HIV-1-Infected Men Who Have Sex with Men Is Negatively Correlated with Peripheral Plasmacytoid Dendritic Cell Counts at the Early Stage of Primary Infection

To explore the relationship between absolute dendritic cell (DC) counts at the early stage of primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) and subsequent disease progression, we performed a prospective study of 16 rapid progressors (RPs) and 12 typical progressors (TPs) from a PHI cohort of men who have sex with men. Significantly decreased plasmacytoid DC (pDC) and myeloid DC (mDC) counts in the blood of RPs were observed at study entry as compared with TPs and healthy HIV-1-negative subjects. Low baseline pDC counts were significantly associated with rapid disease progression after adjustment for baseline CD4(+) T cell counts, mDC counts, and HIV-1 load. Kaplan-Meier survival analysis showed that low pDC counts were strongly associated with rapid disease progression. Our findings demonstrated the predictive value of blood absolute pDC counts at baseline in PHI for HIV-1 disease progression. Further studies are required to confirm this notion.     

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.     

Performance evaluation of Elecsys HIV Duo on cobas e 801 using clinical samples in China

The prevalence and incidence of human immunodeficiency viruses (HIV) infection are rapidly increasing, and novel HIV genotypes are emerging. This study evaluated the sensitivity and specificity of Elecsys HIV Duo assay in population with the epidemic of multiple genotypes of HIV-1 infection. Specificity of the Elecsys HIV Duo assay was determined using 3039 serum samples from patients receiving routine HIV-1 screening tests in China. Sensitivity was assessed with seroconversion panels. Additional 67 positive from newly diagnosed HIV-1 infected samples were also included to test assay performance on various HIV-1 genotypes. The assay performance was compared with that of the Elecsys HIV Combi PT assay. The genotypes of all HIV-1 positive samples were determined with phylogenetic analyses on the 1.1 kb Pro-RT region of pol gene for drug resistance tests. The Elecsys HIV Duo assay had a slightly higher specificity (99.93% vs 99.84%) and equivalent sensitivity to Elecsys HIV Combi PT assay. Seventy-two HIV-1 positive samples, including 12 antigens positive samples, were distinguished by Elecsys HIV Duo. Among them, 43 samples were circulating recombinant form (CRF)01_AE, followed by 13 of CRF07_BC, 10 of subtype B, 4 of URF_0107, 1 of URF_01B and 1 of CRF02_AG. The Elecsys HIV Duo assay showed good performance for the Chinese population with an epidemic of multiple HIV genotypes.     

Associations of HLA Class I antigen specificities and haplotypes with disease progression in HIV-1-infected Hans in Northern China

The human leukocyte antigen (HLA) allele frequencies, which differ among various ethnic populations, may result in population-specific effects on HIV-1 disease progression. No large-scale study has yet been conducted on the Chinese population. In this study, HLA class I antigen specificities were determined in a cohort including 105 long-term non-progressors (LTNPs) and 321 typical progressors (TPs), who were recruited from HIV-1-infected Northern Han Chinese, to determine the associations between certain HLA types and HIV-1 disease progression. The frequencies of HLA class I specificities and haplotypes among the two groups were compared using binary logistic stepwise regression. Results showed that HLA-A^∗30-B^∗13-C^∗06 (OR = 0.387, P = 0.019) and B^∗67 (OR = 0.134, P = 0.005) were associated with a long-term non-progressing condition, and C^∗01 (OR = 2.539, P = 0.050) was overrepresented in TPs after adjusting for non-genetic factors (sex, age, the location of patients, HIV subtype and the route of infection). The influence of HLA homozygosity on HIV disease progression was also analyzed. However, homozygosity at HLA-A, HLA-B or HLA-C conferred no observable disadvantage in our study population (P = 0.730, 0.246 and 0.445, respectively). These findings suggest that the host’s genetics make important contributions to HIV viral control and may help to develop peptide-based vaccines for this population.     

大学生MSM人群HIV感染风险预测模型建立及效果验证研究

目的 建立并验证大学生男男性行为者(men who have sex with men,MSM)的HIV感染风险预测模型。 方法 利用我国7大城市(上海、南京、长沙、郑州、济南、沈阳和昆明)MSM横断面调查数据库中在校大学生MSM相关信息,通过单因素和多因素logistic回归建立模型并采用Stepwise逐步回归法筛选模型变量;采用C-statistics检验、Hosmer-Lemeshow检验(H-L检验)对模型进行判别能力和拟合效果的内部验证和评价;采用Bootstrap重抽样技术进行模型内部验证。 结果 共纳入742名大学生MSM参加研究,其HIV感染率为5.9%(44/742)。经logistic回归模型拟合并通过stepwise法筛选,以下变量进入最终模型:有性传播疾病感染史(OR=5.4,95%CI:2.5~11.4,P<0.01)(5分);近半年使用过新型毒品(OR=2.2,95%CI:1.2~4.2,P=0.016)(2分);最近一次男男性行为方式为被插入方或同时为插入方和被插入方(OR=2.3,95%CI:1.0~5.0,P=0.044)(2分)。模型的C-statistic检验的统计量AUC为0.71,H-L检验的卡方值为1.35(P=0.717);各变量在1 000个Bootstrap样本中出现的频率均>50%。 结论 大学生MSM人群HIV感染风险预测模型具有较好的判别能力和拟合效果,有助于大学生MSM人群比较客观地评估其自身HIV感染风险,以及促进其参与后续HIV检测等防控活动。     

HIV感染者急性期血浆CCL2水平与病毒载量关系分析

目的探究HIV感染者急性期血浆CCL2水平与病毒载量相关性以及动态变化关系。方法选取中国医科大学附属第一医院红丝带门诊HIV感染者54例,对样本的CCL2水平、病毒载量进行分析。结果急性期CCL2表达水平与病毒载量呈正相关(r=0.2920,P=0.0464);急性期CCL2水平与病毒载量存在一致的动态变化关系,在ART中断后,CCL2表达水平随着病毒载量增高而增高。急性期CCL2水平与HIV感染1年时间点的病毒载呈正相关,ROC曲线分析显示急性期血浆CCL2水平对HIV感染1年后病毒载量高低分组(高组≥4.5 Lg copies/mL,低组≤3.5 Lg copies/mL)的预测价值为80.30%(AUC=0.8030,P=0.0444),Kaplan-Meier生存分析显示急性期CCL2 high组(≥12.30pg/mL)的HIV感染者,其发生高水平病毒载量(≥4.5 Lg copies/mL)结局事件所需时间更短(P=0.0339)。结论HIV感染者急性期血浆CCL2水平与病毒载量水平呈正相关,急性期血浆CCL2高表达预示HIV感染者体内更快的疾病进展。CCL2有希望作为一个阻断靶点,限制HIV的侵袭能力。