既往有偿献血(浆)人群中艾滋病毒与丙型肝炎病毒共感染研究

我们通过对我国中部地区90年代中期因有偿献血感染人类免疫缺陷病毒（HIV）的300例患者的血液标本进行HIV、丙型肝炎病毒（HCV）的血清学和分子生物学检测，了解有偿献血HIV感染人群的HCV共感染率、共感染者流行病学和基因型分布特征。     

广东省单纯丙型肝炎病毒及其与人类免疫缺陷病毒共感染者丙型肝炎病毒的基因亚型分析

目的 了解广东省人类免疫缺陷病毒(HW) /HCV共感染者与单纯HCV感染者的感染途径、HCV的基因亚型分布及其遗传特征,为丙型肝炎病毒感染的治疗与预防提供依据. 方法采用巢式逆转录-聚合酶链反应扩增广东省95例HIV/HCV共感染者及99例单纯HCV感染者HCVNS5B基因区域,扩增产物测序后进行HCV基因亚型分析,遗传分析利用MEGA4软件.不同种基因亚型型内基因距离以碱基置换率表示.结果 HIV/HCV共感染者HCV有5种基因亚型,其中6a型占53.7％ (51/95)、3a型占17.9％ (17/95)、1b型占15.8％ (15/95)、3b型占11.6％ (11/95)、1a型占1.0％(1/95);1b亚型内基因距离为6.30％±1.27％,高于其他基因亚型.HIV/HCV共感染者主要通过静脉注射毒品感染(75/95,78.9％),其基因亚型主要为6a型,占60.0％ (45/75).单纯HCV感染者HCV有7种基因亚型,其中1b型占67.7％ (67/99)、6a型占17.2％(17/99)、3a型占6.1％ (6/99)、2a型占5.％(5/99)、3b型占2.0％(2/99)、4a型占1.0％ (1/99)、5a型占1.0％(1/99);1b亚型内基因距离为5.17％±1.03％,高于其他基因亚型.单纯HCV感染者主要通过输血或血液制品感染(80/99,80.8％),其HCV基因亚型主要为1b型,占76.2％ (61/80).结论 广东地区HIV/HCV共感染者及单纯HCV感染者HCV基因亚型呈现多样性,HIV/HCV共感染者与单纯HCV感染者主要感染途径不同,HCV主要基因亚型也不同.     

Impact of treatment with direct-acting antivirals on inflammatory markers and autoantibodies in HIV/HCV co-infected individuals

HCV infection could have extrahepatic manifestations due to an aberrant immune response. HCV/HIV co-infection increases such persistent immune activation. Aim of the present study is to describe the evolution of inflammatory markers used in clinical practice, mixed cryoglobulinemia (MC) and autoantibody reactivity in co-infected individuals who achieved sustained virological response (SVR) after DAA treatment. This prospective, observational study included all HIV/HCV co-infected subjects who started any DAA regimen from 2015 to 2020. Samples for laboratory measurements (ferritin, C reactive protein, C3 and C4 fractions, rheumatoid factor, MC, anti-thyroglobulin Ab, anti-thyroid peroxidase Ab, ANCA, ASMA, anti-LKM, anti-DNA, AMA, ANA, T CD4+ and CD8+ cell count, and CD4/CD8 ratio) were collected at baseline, after 4 weeks, at end of treatment, and at SVR12. The analysis included 129 individuals: 51.9% with a F0–F3 fibrosis and 48.1% with liver cirrhosis. Cryocrit, C3 fraction, and rheumatoid factor significantly improved at week 4; ferritin, anti-thyroglobulin Ab, and C4 fraction at EOT; total leukocytes count at SVR12. MC positivity decreased from 72.8% to 35.8% (p < .001). T CD4+ cell slightly increased at SVR12, but with an increase also in CD8+ resulting in stable CD4/CD8 ratio. Autoantibody reactivity did not change significantly. ANA rods and rings positivity increased from 14.8% to 28.6% (p = .099): they were observed in three subjects without exposure to RBV. DAA therapy may lead to improvement in inflammatory markers and MC clearance but without significant changes in autoantibodies reactivity and CD4/CD8 ratio over a follow up of 12 weeks.     

血友病合并HIV/HCV感染者肝功能异常的相关因素分析

目的探讨血友病合并艾滋病病毒/丙型肝炎病毒(HIV/HCV)感染者CD4计数和HIV病毒载量,与HIV/HCV重叠感染者肝功能异常的相关性。方法观察了63例血友病合并HIV/HCV感染者,据CD4计数和HIVRNA阳性情况,比较肝功能异常的发生率与细胞免疫、HIVRNA阳性的相关性。结果CD4≤200细胞/mm3者20例中,有肝功能异常者14例,与CD4计数>200细胞/mm3组肝功能异常发生率有统计学差异(P<0.05)。HIVRNA阳性的38例中,有肝功能异常者22例,与HIVRNA阴性组肝功能异常发生率有统计学差异(P<0.05)。肝功能异常组的CD4计数较肝功能正常组为低,HIVRNA定量较正常组为高,其差异有统计学意义(P<0.05)。结论CD4计数和HIVRNA阳性情况,可作为血友病合并HIV/HCV感染者肝功能异常的预测因素。     

HBV合并HCV或人类免疫缺陷病毒感染的抗病毒治疗进展

乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染是目前全球慢性肝病的主要原因,HBV合并人类免疫缺陷病毒(HIV)感染也较常见,全球4000万HIV感染者中10%并发慢性乙型肝炎(CHB).自从高效抗逆转录病毒治疗的推广,艾滋病相关原因的死亡已经减少,但由肝脏疾病造成的死亡却不断上升,逐渐成为HIV感染者发病和死亡的一个主要原因.     

沈阳地区650例慢性丙型肝炎病毒感染者的病毒基因型分析

HCV感染呈全球分布,不同基因型和亚型的地理分布,可能与抗HCV治疗的疗程及效果相关.本研究以核酸序列分析法对650例患者进行HCV基因型检测分析,以探讨沈阳地区感染人群中HCV的基因型特征.一、资料与方法     

Baseline risk factors for relapse in HIV/HCV co-infected patients treated with PEG-IFN/RBV

Purpose

Hepatitis C virus (HCV) viral relapse (VR) after end-of-treatment response (ETR) in human immunodeficiency virus (HIV) co-infected patients is observed in as many as one in three co-infected patients. The aim of the study was to identify baseline risk factors for VR in HIV/HCV co-infected patients treated with pegylated interferon plus ribavirin (PEG-INF/RBV).

Methods

A total of 212 Caucasian HIV-infected patients with chronic hepatitis C naïve for PEG-INF/RBV were followed prospectively. Patients were included in this prospective study if they had completed a full course of therapy with an ETR. We assessed the relationship between VR rate and potential predictors of relapse.

Results

Of the patients followed, 130 (61.3 %) attained ETR and 103 (79.2 %) achieved sustained virological response (SVR). Consequently, 27 (20.8 %) showed VR. Patients who relapsed were more often male (p = 0.036), carried the non-CC rs14158 genotype in the low-density lipoprotein receptor (LDLr) gene (p = 0.039), had higher baseline HCV RNA levels (p = 0.012), body mass index (BMI) ≥25 kg/m² (p = 0.034), significant liver fibrosis (p < 0.001), had been diagnosed with acquired immunodeficiency syndrome (AIDS)-defining criteria in the past (p = 0.001) and bore the HCV genotypes 1/4 (p = 0.046) when compared with SVR patients. The IL28B genotype was not associated with relapse. Multivariate binary logistic regression showed that high baseline HCV RNA, significant liver fibrosis, HCV genotypes 1/4, being overweight and being diagnosed with AIDS-defining criteria in the past were independently associated with relapse.

Conclusions

Our study shows that VR can be accurately predicted in HIV/HCV co-infected patients on the basis of risk factors which can be identified before treatment.     

High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

Background

Anti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxis and after cessation of prophylaxis.

Methods

Between 22 Jun and 16 Jul 09, we performed a cohort study in 3 outbreaks in the Singapore military where post-exposure oseltamivir ring chemoprophylaxis (75 mg daily for 10 days) was administered. The entire cohort was screened by RT-PCR (with HA gene primers) using nasopharyngeal swabs three times a week. Three blood samples were taken for haemagglutination inhibition testing - at the start of outbreak, 2 weeks after completion of 10 day oseltamivir prophylaxis, and 3 weeks after the pandemic's peak in Singapore. Questionnaires were also administered to collect clinical symptoms.

Results

237 personnel were included for analysis. The overall infection rate of 2009 Influenza A (H1N1) during the three outbreaks was 11.4% (27/237). This included 11 index cases and 16 personnel (7.1%) who developed four-fold or higher rise in antibody titres during oseltamivir prophylaxis. Of these 16 personnel, 8 (3.5%) were symptomatic while the remaining 8 personnel (3.5%) were asymptomatic and tested negative on PCR. Post-cessation of prophylaxis, an additional 23 (12.1%) seroconverted. There was no significant difference in mean fold-rise in GMT between those who seroconverted during and post-prophylaxis (11.3 vs 11.7, p = 0.888). No allergic, neuropsychiatric or other severe side-effects were noted.

Conclusions

Post-exposure oseltamivir prophylaxis reduced the rate of infection during outbreaks, and did not substantially increase subsequent infection rates upon cessation. Asymptomatic infections occur during prophylaxis, which may confer protection against future infection. Post-exposure prophylaxis is effective as a measure in mitigating pandemic influenza outbreaks.     

Cognitive impairment in HIV and HCV co-infected patients: a systematic review and meta-analysis

Cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections. However, in the context of HIV/HCV co-infection the research is more limited. The aim of this systematic review was to describe the characteristics of cognitive impairment in HIV/HCV co-infection and to examine the differences in cognitive performance between HIV/HCV and HIV and HCV mono-infected patients. Of the 437 records initially screened, 24 papers met the inclusion criteria and were included in the systematic review. Four studies were included in the meta-analysis. Most studies indicated that HIV/HCV co-infected patients had a higher level of cognitive impairment than HIV mono-infected patients. Meta-analysis also indicated that HIV mono-infected patients had a significantly lower global deficit score than co-infected patients. The results also indicated that co-infected patients were more likely to be impaired in information processing speed than HIV mono-infected patients. These findings can be challenged by biasing factors such as the small number of included studies, heterogeneity of the samples and a large diversity of methodological procedures. Future research with consistent and comprehensive neuropsychological batteries and covering a greater diversity of risk factors is needed, in order to clarify the effects of both viruses on cognitive function and the mechanisms that underlie these effects. Because cognitive impairments may pose significant challenges to medication adherence, quality of life and overall functioning, such knowledge may have important implications to the planning and implementation of effective interventions aimed at optimising the clinical management of these infections.     

高效抗逆转录病毒治疗43例血友病合并丙型肝炎和艾滋病患者3年临床观察

目的了解经高效抗逆转录病毒治疗(HAART)血友病合并丙型肝炎和艾滋病患者的临床疗效与不良反应。方法采用流式细胞仪定期检测CD4、CD3、CD8、自然杀伤细胞(NK)细胞计数;采用FDA推荐的病毒载量检测方法(bDNA)随访血浆病毒载量。结果43例患者在治疗3年后CD4+T淋巴细胞平均上升至257/mm3(P<0.001);HIVRNA平均降低至(2.26±1.10)log/ml(P<0.01)。结论HAART能有效抑制血友病合并丙型肝炎和艾滋病患者体内HIV的复制,有利于免疫功能重建。     

Genotypic distribution of hepatitis C among hepatitis C and HIV co-infected patients in Brazil

Information on hepatitis C virus (HCV) genotypic distribution among HIV-HCV co-infected patients is lacking in Brazil as well as other Latin American countries. The objective of this study was to evaluate the level of exposure to different risk factors associated with HCV transmission among a group of co-infected patients and to characterize the genotypic distribution of HCV in this cluster. A series of 100 HIV-HCV co-infected patients was analysed. The data to be analysed were collected from specific laboratory tests. Information was collected through a questionnaire. HCV genotyping was carried out by sequencing the 5' non-coding region of HCV. Chi-square and Fischer association tests or Kruskal-Wallis test were used to study the association between HCV transmission-related variables and the established genotypes. In conclusion, exposure to multiple risk factors associated with HCV transmission was common among HIV co-infected patients and an association between HCV genotype 3 and intravenous drug user was observed.     

西安及周边地区HCV基因型构成分析

正HCV可分为6个主要类型(1、2、3、4、5和6型),每个类型又可以继续分为多种亚型[1]。HCV基因组高突变率的特点极大的阻碍了疫苗及治疗性抗体的研发。中国现行HCV标准治疗方案主要依赖于聚乙二醇干扰素(PEG-IFN)联合利巴韦林[2],但随着新的直接抗病毒药物(direct acting antiviral agents,DAA)的研发及临床运用,病毒清除率得到极大的提高,HCV NS5蛋白酶抑制剂——索非布韦(sofosbuvir)能够有效抑     

Differential antiviral effect of PEG-interferon-alpha-2b on HIV and HCV in the treatment of HIV/HCV co-infected patients

OBJECTIVE: The major antiviral effect of interferon (IFN)-alpha on hepatitis C virus (HCV) is blocking of virion production from infected cells. We now investigate the previously unknown mechanism of action of IFN-alpha against HIV. METHODS: HIV kinetics in parallel to HCV kinetics and IFN pharmacokinetics during pegylated-IFN-alpha-2b (1.5 microg/Kg q.w., PEG-IFN) and ribavirin (1-1.2 g daily) treatment in nine HIV patients co-infected with HCV genotype 1 were analyzed. In vivo modeling predictions of suppression of HIV replication by PEG-IFN in CD8-depleted peripheral blood mononuclear cells were verified by in vitro experiments. RESULTS: HCV and HIV show different viral decline patterns after administration of PEG-IFN. Unlike the bi-phasic decline shown by HCV, HIV shows a slow continuous decline during the first week, with no rebound when PEG-IFN levels decline. Fitting of HIV kinetics with known half-lives of free virus and infected cells indicates that the major effect of IFN on HIV is to block de novo infection rather than to block virion production. The magnitude of the antiviral effect is similar (mean 1.1 log10 decline at 7 days) to those of direct anti-HIV drugs, but shows an inverse correlation with baseline viremia. In vitro studies show that preincubation with IFN renders a suppression of HIV replication superior to that of treatment postinfection, thus corroborating the mathematical analysis in vivo. CONCLUSION: The complimentary antiviral properties of IFN-alpha and antiretroviral therapy suggest a role for pharmacokinetically improved formulations of IFN as part of salvage therapy for HIV-infected individuals.     

某医院HIV感染者中HBV HCV TP混合感染状况分析

目的 了解综合性医院首诊艾滋病病毒(HIV)感染者中合并乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)和梅毒螺旋体(TP)的混合感染情况及临床特点,为艾滋病(AIDS)的防控和治疗提供科学依据.方法 2013年1月至2017年12月,以非艾滋病首诊于某综合性医院而确证为HIV感染者,收集其人口学资料和临床资料,并进行乙...     

Fibrosis progression in paired liver biopsies from HIV/HCV co-infected patients

Background

Chronic hepatitis C is more aggressive during HIV infection. Available data about risk factors of liver fibrosis in HIV/HCV co-infected patients derive from studies based on a single liver biopsy.

Objectives

To evaluate the risk factors of liver fibrosis progression (LFP) and to investigate the role of antiretroviral therapy (ARV) in HIV/HCV patients who underwent paired liver biopsy.

Patients and Methods

We retrospectively studied 58 patients followed at two Infectious Diseases Departments in Northern Italy during the period 1988-2005. All specimens were double-blinded and centrally examined by two pathologists. LFP was defined when an increase of at least one stage occurred in the second biopsy, according to the Ishak-Knodell classification.

Results

In a univariate analysis, serum levels of alanine aminotransferase (ALT) > 150 IU/L at the first biopsy (P = 0.02), and a > 20% decrease in CD4+ cell count between the two biopsies (P = 0.007), were significantly associated with LFP. In multivariate analysis, a > 20% decrease in CD4+ cell count remained independently associated to LFP (Odds Ratio, 3.99; 95% confidence interval, 1.25-12.76; P < 0.02). Analysis of life survival curves confirmed the correlation between CD4+ cell count and LFP.

Conclusions

Our findings highlight that in HIV/HCV coinfected patients, an effective antiretroviral therapy that assures a good immune-virological profile contributes to reducing the risk of LFP.     

Association between depressive symptoms,CD4 count and HIV viral suppression among HIV-HCV co-infected people

Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security &; HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300–665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4?=?0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.     

Role of rapid virological response in prediction of sustained virological response to Peg-IFN plus ribavirin in HCV / HIV co-infected individuals

Summary.  The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. 65 HIV / HCV co-infected patients commenced HCV treatment per protocol. HIV / HCV patients with a mean CD4 count of 502 were treated for 24–48 weeks depending on genotype. Virological response was assessed at weeks 4 (RVR), 12 [early virological response (EVR)], 24, at end of treatment (EOTR) and 24 weeks post-completion of treatment (SVR). Primary end-point was defined as undetectable HCV RNA at 24 weeks post-treatment completion. Fifty-five per cent of co-infected patients were on highly active anti-retroviral therapy. A majority of patient group were male. 60% of HIV / HCV patients achieved SVR (35% genotype 1 / 4; 77% genotype 2 / 3). 24 HIV / HCV patients achieved undetectable HCV levels compared with baseline by week 4. The positive predictive value (PPV) of RVR at week 4 for subsequent SVR in HIV–HCV co-infected patients was 100%; the negative predictive value (NPV) was 57%. Significant variables associated with SVR were: (i) lower median pre-treatment HCV viral load, (ii) genotype 2 / 3 disease and (iii) achievement of RVR. Independent variables associated with RVR were low pre-treatment HCV viral load and genotype 2 / 3 disease. Achievement of RVR, a negative HCV-PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups. More significantly, the data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients co-infected with G2 / 3 disease for whom 6 months' full dose therapy may be sufficient to obtain a SVR.