HIV/Hepatitis B and C co-infection: pathogenic interactions, natural history and therapy

Recent advances in antiretroviral therapy for HIV infection have substantially improved overall mortality, as well as morbidity from life-threatening opportunistic infections. In place of the usual HIV-associated opportunistic infections, morbidity and mortality due to the sequelae of hepatitis B (HBV) and C virus (HCV) infections have taken on a leading role in HIV-infected individuals. This review will examine the pathogenesis of these viruses in the setting of co-infection and the effect of immunosuppression with HIV, the natural history of co-infection, with particular attention to the effect on serological and histological markers, and the effect of immune reconstitution on the course of HBV and HCV infection. Consideration will also be given to the effect of HIV infection on HBV and HCV load (especially for HCV) and progression of liver disease. Finally, we will discuss the rapidly evolving area of therapy, with particular attention to many of the newer agents now in clinical trials, as well as combinations of these agents.     

CD81和趋化因子CC受体5与丙型肝炎合并人类免疫缺陷病毒感染的相关性研究

目的 检测外周血CD4＋及CD8＋T淋巴细胞表面CD81、CCR5的表达,探讨与丙型肝炎病毒（HCV）单纯感染、人类免疫缺陷病毒（HIV）单纯感染和HCV/HIV合并感染的关系.方法 采用流式细胞术,检测HCV感染组（n=21）、HIV感染组（n=14）、HCV/HIV感染组（n=28）及正常对照组（n=30）人外周血CD4＋及CD8＋T淋巴细胞表面CD81和CCR5的表达.结果 与正常对照组相比,外周血CD4＋T淋巴细胞表面CD81,在HCV感染组表达变化不明显,而在HIV感染组和HCV/HIV合并感染组中低表达;CD8＋T淋巴细胞表面CD81,在HCV感染组、HIV感染组和HCV/HIV合并感染组中都呈高表达.外周血CD4＋T和CD8＋T淋巴细胞表面CCR5,在HIV感染组高表达,而在HCV感染组和HCV/HIV合并感染组中低表达.结论 HCV/HIV合并感染中,影响外周血CD4＋及CD8＋T淋巴细胞表面CCR5表达的主要因素是HCV感染;而合并感染对CD4＋及CD8＋T淋巴细胞表面CD81的表达,其影响作用是不相同的.     

大理市HIV感染者中HCV感染状况的研究

目的探讨人类免疫缺陷病毒(HIV)-1感染者中丙型肝炎病毒(HCV)的混合感染率,并了解HCV对HIV-1感染者CD4+T细胞计数的影响。方法采用横断面研究方法,在云南大理市招募HIV-1感染者,分别采用血清学和核酸方法检测HCV混合感染。结果在526例HIV-1感染者中,静脉吸毒者占94.3%,其余为性途径感染。86.9%(457/526)为HCV血清学检测抗体阳性,其中HCV核酸阳性者占78.3%。在HCV血清学阴性的69例中,24例HCV RNA>1 000 IU/mL。由于引入HCV核酸检测方法,现场HCV混合感染的发现率增加了4.6%(24/526),所调查的HIV-1感染者中HCV混合感染率为91.4%。HCV混合感染者的CD4+T细胞计数明显低于HIV-1单纯感染者。结论在HCV感染的高流行区或髙危人群中,HCV与HIV-1共感染率较高。筛查HIV-1感染时应加强对HCV的检测,有助于对HCV感染进行早期诊断并开展HCV的早期治疗,减少HCV对HIV-1感染者的不利影响。     

安徽、河南、山西3省自愿咨询检测人群HIV/HCV共感染及HCV基因亚型初步分析

目的了解目前我国安徽、河南、山西3省自愿咨询检测(VCT)人群HIV感染者中HIV/HCV共感染率及HCV亚型的分布情况。方法对来自安徽、河南、山西3省VCT人群中HIV阳性样本进行HCV抗体检测并对HCV阳性的样本进行HCVC/E1区RT-PCR扩增、基因测序,分析HCV的亚型分布。结果在HIV阳性的382份样本中,检出HCV阳性215份,3省VCT人群HIV感染者中HIV/HCV共感染率平均为56.3%,安徽、河南、山西3省分别为50.0%、59.3%、42.9%。其中,经血传播人群的HIV/HCV共感染率为72.1%,经性传播人群为33.3%,其它途径人群为36.6%。HCV PCR扩增成功98份,1b亚型69份(70%),2a亚型28份(29%),3a亚型1份(1%)。结论安徽、河南、山西VCT人群具有较高的HIV/HCV共感染率;经性传播人群HIV/HCV共感染率高于国外水平;HIV/HCV共感染对HCV亚型分布无显著影响。     

Pegylated-IFNα2a for HIV/hepatitis C virus coinfected patients: out with the old,in with the new

Introduction: Liver disease is a major burden in patients co-infected with HIV and hepatitis C virus (HCV). From the time of its approval, pegylated-IFNα-2a (pegIFN-α2a) has played a major role in treatment of HCV in HIV/HCV co-infection.

Areas covered: This article briefly summarizes the epidemiology of HCV/HIV co-infection, the pharmacokinetic, and pharmacodynamic properties of pegIFN-α2a. Results from clinical trials investigating therapies containing pegIFN-α2a for HIV/HCV co-infected patients will be discussed with a focus on efficacy and safety.

Expert opinion: PegIFN-α2a has improved rates of sustained virologic response for co-infected patients. In combination with direct-acting antivirals (DAA), the disparity between mono- and co-infected patients is beginning to disappear. For the first time, IFN-free regimens are available in clinical practice. It is unlikely that pegIFN-α2a will continue to be a critical component in treatments for HCV in the general co-infected population.     

中国HCV/HIV合并感染者T淋巴细胞表面CD81、CXCR3表达的研究

目的探讨T淋巴细胞表面受体CD81、CXCR3，在丙肝病毒（HCV）单纯感染，艾滋病病毒（HIV）单纯感染和HCV／HIV合并感染过程中的表达及意义。方法采用流式细胞术，检测HCV感染组（n=21），HIV感染组（n=14），HCV／HIV感染组（n=28）及正常对照组（n=30）人外周血CD4^＋T淋巴细胞和CD8^＋T淋巴细胞表面CD81、CXCR3的表达。结果HIV感染组及HCV／HIV合并感染组CD4^＋T细胞表面CD81、CXCR3表达显著降低（P〈0．001），CD8^＋T细胞表面CD81、CXCR3表达显著升高（P〈0．001）；HCV感染组CD4^＋及CD8^＋T细胞表面CXCR3表达轻度升高但差异不显著，CD81在CD4^＋T细胞表面轻度升高而在CD8^＋T细胞表面明显升高（P〈0．01）。结论中国HCV／HIV合并感染患者外周血T淋巴细胞表面受体CD81、CXCR3，在CD4^＋T细胞表面表达降低，而在CD8^＋T细胞表面表达升高。     

Treatment of chronic hepatitis C patients complicated with the other disease

Because of relatively low efficacy, considerable side effect and high cost, HCV infected patients complicated with the other disease(patients with hematologic dysorders, chronic renal failure on hemodialysis, HIV co-infection and collagen disease) have been excluded from large trials evaluating the efficacy of IFN or in combination with ribabirin. So, little is known about treatment of these patients. We analyzed the medical literature focusing on treatment of HCV infection in these patients, to suggest conclusion about indication based on tolerance and efficacy. In case the other disease is well controlled and long term sevival is expected, treatment should be required based on the evaluation of liver function test including liver pathology for preventing liver disease from developing terminal stage. Further studies are needed to better define HCV therapies in these patients.     

Co-infection of HBV with HCV and a possible role of HBV DNA in hepatocarcinogenesis

HBV and HCV are two major etiologic agents of chronic hepatitis, which is closely related to the development of hepatocellular carcinoma (HCC). A possible involvement of HBV co-infection was investigated in ongoing HCV-related liver diseases in HCV-infected patients. A high prevalence of anti-HBC in anti-HCV-positive/HBsAg-negative chronic hepatitis patients was found and a low copy number of HBV DNA was detected in most of the liver biopsy samples of anti-HCV-positive/HBsAg-negative patients. The current data suggest that HBV co-infects frequently with HCV and may play an important role in the development of HCC in HCV-infected patients.     

HIV-1感染者中HCV混合感染情况分析

目的：调查我国不同地区、通过不同传播途径感染人类获得性免疫缺陷病毒I型（HIV－1）患中丙型肝炎病毒（HCV）的流行情况及不同亚型的分布。方法：采用酶联免疫吸附试验（ELISA）检测抗－HIV－1并以蛋白印迹试验（Western blot,WB)进行确认。采用DNA分支放大（bDNA)技术检测HIV－1病毒载量，采用荧光抗体流式细胞检测技术（FACs)作CD4和CD8细胞计数。抗－HCV检测采用ELISA方法。HCV基因亚型的测定采用实时（real-time)聚合酶链反应（PCR）方法。结果：共检测了239例HIV－1感染，抗－HCV阳性率为56．9％（136／239），其中经不同传播途径感染HCV的阳性率分别为：静脉注毒：42．7％（58／136）；经血液：53．7％（73／136）；性接触途径：3．7％（5／36）。静脉注毒（云南和新疆）HCV感染以1，3，4亚型最多，而输血人群（河南省）感染的HCV以1，2亚型为主。结论：HIV－1感染中存在HCV混合感染，我国HCV基因亚型以1型为主。     

Prevalence of hepatitis B and hepatitis C viral infections in Indian patients with chronic renal failure

The present study reports prevalence of posttransplant hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in 256 patients with chronic renal failure (CRF) and with a history of either renal transplant or hemodialysis. Out of 256 patients 138 had renal transplant and 118 were on maintenance hemodialysis. Among the patients screened, 7% had HBV infection alone, 46% were infected with HCV alone, while 37.10% were found to have co-infection of both the viruses. Our findings implicate these viruses as the major cause of posttransplant hepatitis in Indian patients with CRF and indicate implementation of stringent screening procedures for these two viral infections.     

Optimum combination therapy regimens for HIV/HCV infection

HIV-HCV co-infection mostly affects intravenous drug users, in whom prevalence has tended to decrease in recent years, while it has increased in men who have sex with men, with occurrence of acute hepatitis C. Hepatitis C has a poorer prognosis in patients co-infected with HIV, as clinical progression is faster and degree of hepatic fibrosis is greater. However, optimized ARV treatment is clearly associated with slower progression to hepatic complications. Interactions between HCV and HIV drugs are numerous, which underlines the importance of pharmacological advice for HIV-treated patients before they start HCV treatment. In HIV-HCV co-infection, treatment of hepatitis C has to be offered as in mono-infected patients (US and European countries) or to all patients (French guidelines). In most patients, HCV eradication is achieved with different DAA associations, the choice and duration being driven by HCV genotype, hepatic fibrosis stage, and whether patients have been previously treated or not.     

广州地区HIV感染者的临床和流行特征分析

目的：了解人类免疫缺陷病毒(HIV)感染者中HIV感染途径、HIV／HBV及HIV／HCV合并感染情况和机会性感染的发生率及类型。方法：检测HIV感染者／获得性免疫缺陷综合征(AIDS)患者HBV、HCV感染标志，确定HIV／HBV、HIV／HCV合并感染情况，了解其HIV感染途径，对是否存在机会性感染情况进行临床和实验室指标的综合诊断。结果：55例HIV感染者中静脉吸毒、性接触、输血或血制品及垂直传播分别占40％、36．4％、20．0％及3．6％。HIV／HBV、HIV／HCV合并感染率分别为16．4％和41．8％，两者比较有显著差异。机会性感染发生率为85．5％，感染类型由高至低依次为：肺炎、口腔毛状黏膜白斑(OHL)、口腔真菌感染、各种感染性腹泻、各种结核病、败血症、疱疹病毒感染。结论：广州地区HIV感染途径由高到低的顺序为：静脉吸毒传播、性传播、输血或血制品传播、母婴传播，其中以静脉吸毒和性接触方式感染为主。广州地区存在HIV／HBV、HIV／HCV合并感染情况，尤其是HIV／HCV合并感染率情况较严重；来医院住院治疗的HIV感染者绝大部分为已发生机会性感染的AIDS患者。     

Cholesterol levels in HIV-HCV infected patients treated with lopinavir/r: results from the SCOLTA project.

BACKGROUND: It is not known whether antiretroviral therapy (ART) including lopinavir/r has a different effect on the lipid metabolism in HIV patients co-infected with HCV. This study investigated changes in lipid levels, comparing patients with HIV infection alone and those with HCV too, in the lopinavir/r cohort of the SCOLTA project. METHODS: We analyzed the data for the lopinavir/r nationwide cohort from 25 Italian infectious disease departments, which comprises 743 HIV-infected patients followed prospectively, comparing subjects with HIV-HCV co-infection and those with single-infection. RESULTS: At enrolment, co-infected patients had significantly lower mean cholesterol than HCV negative cases (162+/-43mg/dL vs. 185+/-52mg/dL, p=0.0009). Total and non-HDL cholesterol and triglycerides rose significantly from baseline in HIV single-infection patients, but not in those with co-infection. The patients with dual HIV-HCV infection, treated with an ART regimen including lopinavir/r, have only limited increases in total and non-HDL cholesterol and triglycerides. CONCLUSIONS: Changes in serum lipids in co-infected patients differed significantly from those in patients without HCV. It remains to be seen whether this is associated with a lower risk of progression of atherosclerotic disease.     

Depressive symptoms after initiation of interferon therapy in human immunodeficiency virus-infected patients with chronic hepatitis C

BACKGROUND: Interferon alpha (IFN-alpha) therapy for chronic hepatitis C (CHC) infection is commonly associated with neuropsychiatric side effects including depressive symptomatology. In this study, we evaluated the incidence and management of depressive symptoms during IFN-alpha therapy in HIV-infected patients with CHC. METHODS: HIV-infected patients with CHC who began IFN-alpha and ribavirin therapy during the recruitment period April 2001 to April 2003 were included in the study. Patients with a history of major depressive disorder were excluded. RESULTS: Of 113 co-infected patients who started IFN-alpha therapy during the recruitment period, 45 (40%) developed symptoms of depression (sadness, tiredness and apathy). Twenty of them (44%) were treated with citalopram, a selective serotonin re-uptake inhibitor, resulting in a significant improvement in their symptoms. Most of the patients (60%) showed depressive side effects in the first 3 months after initiation of IFN-alpha. In addition, during the study, three patients developed psychotic symptoms and one committed suicide. CONCLUSIONS: The incidence of depressive symptoms in patients with HIV/HCV co-infection treated with IFN-alpha is high. Most of the depressive symptoms were not severe and improved with antidepressant therapy, without reduction or cessation of IFN-alpha therapy. During the first weeks after initiating IFN-alpha therapy for HIV/HCV co-infection, close assessment of psychiatric symptoms is recommended. Early treatment of these side effects with antidepressants would help avoid early dropouts from interferon therapy.     

Simultaneous detection of HCV and HIV-1 by SYBR Green real time multiplex RT-PCR technique in plasma samples

This paper describes the development of a SYBR Green-based multiplex real time RT-PCR for the simultaneous detection of HCV and HIV-1 genomes in plasma samples. Viral genomes were identified in the same sample by their distinctive melting temperature (Tm) which are 81.6 and 86.5 degrees C for HIV-1 gag 142 bp amplicon and HCV 5'-NCR region 226 bp amplicon, respectively. Analysis of known scalar concentrations of reference plasma indicated that the multiplex procedure detects at least 500 copies/ml of both HIV-1 and HCV. In addition, we also assayed HIV-1 and HCV viral load in 30 co-infected patients and in 15 blood donors, confirming the sensitivity and specificity of the assay. This method may represent a useful alternative method for the detection of HIV-1/HCV co-infection, reliable for a rapid and relatively inexpensive screening of blood donors.     

Lateral rectus muscle paralysis induced by ribavirin and pegylated interferon-α2a in a patient with HIV/HCV co-infection

We report a lateral rectus muscle paralysis occurring 2 weeks after initiation of an interferon-α and ribavirin treatment in a patient with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) virus co-infection. This patient presented with horizontal diplopia that appeared rapidly and without any other neurological symptoms. Symptoms fully resolved with treatment interruption without any ophthalmological sequelae. This side effect is rare and has never been reported in a HIV–HCV co-infected patient.     

不同送检人群HIV、TP和HCV合并感染分析

目的分析人类免疫缺陷病毒(HIV)、梅毒(TP)和丙型肝炎病毒(HCV)合并感染现象在不同送检人群中的表现。方法采用酶联免疫吸附试验和病毒核酸检测192例不同送检人群感染HIV、TP和HCV的情况,分析合并感染的特点。结果 192例送检血液标本均感染HIV,男127例,女65例,其中51例合并感染TP,18例合并感染HCV,7例同时感染以上3种病毒;合并感染者以血液科、传染科、皮肤科、肝病科和戒毒所送检的血液标本为主。结论 HIV与TP和HCV往往呈二重或多重合并感染,加强HIV感染者的健康教育和行为干预意义重大。     

浙江省温州市吸毒人员中四种性传播疾病感染状况及影响因素调查

目的 了解浙江省温州市吸毒人员艾滋病病毒(HIV)、乙型病毒性肝炎病毒(HBV)、丙型病毒性肝炎病毒(HCV)以及梅毒螺旋体(TP)感染状况及影响因素,为开展干预工作,预防控制相关疾病在该类人群中流行提供依据。 方法 2011年新入住温州市强制戒毒所戒毒的人员作为本次调查对象进行匿名问卷调查,采集静脉血进行HIV、HBV、HCV、TP血清学检测,并对结果进行统计分析。 结果 403名吸毒人员HIV、HBV、HCV、TP阳性率分别为0.50%、16.87%、55.09%和9.68%。合并HBV/HCV、HBV/TP二重感染分别占60.49%和8.64%,HBV/HCV/TP、HIV/HBV/HCV三重感染分别占27.16%和2.47%,HIV/HBV/HCV/TP四重感染占1.23%。 结论 吸毒人员是HIV、HBV、HCV、TP感染的高危人群,应加强对该类人群的宣传教育和行为干预,以降低这几种疾病在该人群中的传播和扩散。     

Faldaprevir (BI 201335) for the treatment of hepatitis C in patients co-infected with HIV

Chronic HCV infection affects 130–170 million individuals worldwide and there are currently 34 million people living with HIV/AIDS. The aim of treatment of HCV is the elimination of the virus (sustained virological response). With development of drugs that specifically target HCV replication, direct-acting agents, sustained virological response rates have dramatically changed for genotype 1 infections. Challenges in the use of direct-acting agents in patients with HIV/HCV co-infection include the potential for drug–drug interactions between HIV and HCV drugs, additional drug toxicities and the need for therapy with IFN-α. Faldaprevir (FDV), previously known as BI 201335, is a second-wave HCV NS3/4A protease inhibitor with highly potent in vitro activity against HCV GT-1a/1b and improved pharmacokinetics suitable for once-daily dosing. FDV is currently in Phase III development. This article will review the pharmacology and pharmacodynamics of FDV, the efficacy and safety of the drug and explore possible future developments in the management of chronic hepatitis C infection, focusing on HIV/HCV co-infected patients.     

Hepatitis C virus therapies: current treatments,targets and future perspectives

Chronic hepatitis C virus (HCV) infection is the cause of an emerging global epidemic of chronic liver disease. Current combination therapies are at best 80% efficacious and are often poorly tolerated. Strategies to improve the therapeutic response include the development of novel interferons, nucleoside analogues with reduced haemolysis compared with ribavirin and inosine 5'-monophosphate dehydrogenase inhibitors. Compounds in preclinical or early clinical trials include small molecules that inhibit virus-specific enzymes (such as the serine proteases, RNA polymerase and helicase) or interfere with translation (including anti-sense molecules, iRNA and ribozymes). Advances in understanding HCV replication, obtaining a sub-genomic replicon and contriving potential small animal models, in addition to solving crystallographic structures for the replication enzymes, have improved prospects for developing novel therapies. This review summarizes current and evolving treatments for chronic hepatitis C infection. In addition, progress in HCV targets and drug discovery tools valuable in the search for novel anti-HCV agents is detailed.