Hepatitis C-HIV coinfection: current and future therapy

Coinfection with hepatitis C in HIV-infected patients has been reported in 15-70% of patients depending on the mode of acquisition of both viruses. As recent advances in HIV-directed antiviral therapy have markedly delayed HIV progression and mortality, the incidence of complications arising from hepatitis C-associated liver disease in coinfected patients is increasing exponentially. The interaction of HIV and hepatitis C is complex. It is clear that HIV infection negatively affects the natural history of hepatitis C, while HIV-directed therapy may enhance immunologic response and exacerbate hepatocellular injury induced by hepatitis C via immune reconstitution. In this review, the pathobiology, inter-relation of hepatitis C and HIV infection in coinfected patients as well as present and future treatment in this unique patient population are discussed.     

Hepatitis C–HIV coinfection: current and future therapy

Coinfection with hepatitis C in HIV-infected patients has been reported in 15–70% of patients depending on the mode of acquisition of both viruses. As recent advances in HIV-directed antiviral therapy have markedly delayed HIV progression and mortality, the incidence of complications arising from hepatitis C-associated liver disease in coinfected patients is increasing exponentially. The interaction of HIV and hepatitis C is complex. It is clear that HIV infection negatively affects the natural history of hepatitis C, while HIV-directed therapy may enhance immunologic response and exacerbate hepatocellular injury induced by hepatitis C via immune reconstitution. In this review, the pathobiology, inter-relation of hepatitis C and HIV infection in coinfected patients as well as present and future treatment in this unique patient population are discussed.     

Towards the prevention of transfusion-transmitted infectious diseases

Transfusion-transmission of viral infections, such as HIV and hepatitis C virus, were once the scourge of blood transfusion. However, due to remarkable progress over the last 30 years, tests for viral proteins, antibody responses and more recently, viral nucleic acids, have virtually eliminated these risks. This review summarizes these advances in an historical context, describes new methodologies on the horizon, and discusses residual infectious risks associated with blood transfusion.     

Hepatitis A virus-associated fulminant hepatitis with human immunodeficiency virus coinfection

Hepatitis A virus (HAV) commonly causes acute hepatitis in humans and is transmitted through the fecal-oral route or by ingestion of contaminated food or water. HAV infection generally follows a self-limiting course; it can seldom cause fulminant hepatitis that increases the risk of mortality. To the best of our knowledge, this is the first reported fatal case of fulminant hepatitis caused by HAV in a 40-year-old male with human immunodeficiency virus (HIV) infection. The HAV genotype in this case was IA, which has recently become common globally among people living with HIV (PLWHIV), intravenous drug users, and homeless people especially in developed countries. His HIV infection was stabilized by antiretroviral drugs and his CD4 values were stable. He developed acute hepatic encephalopathy, did not respond to repeated plasma exchange therapy, and died rapidly. It is known that HIV co-infection sometimes leads to fulminant non-HAV hepatitis, although evidence supporting a correlation between fulminant hepatitis A risk and HIV infection is still lacking. This case demonstrated the fatal risk of HAV infection in PLWHIV; it was suggested that education about appropriate preventive measures and vaccination are important for preventing HAV infections among PLWHIV.     

Towards the prevention of transfusion-transmitted infectious diseases

Transfusion-transmission of viral infections, such as HIV and hepatitis C virus, were once the scourge of blood transfusion. However, due to remarkable progress over the last 30 years, tests for viral proteins, antibody responses and more recently, viral nucleic acids, have virtually eliminated these risks. This review summarizes these advances in an historical context, describes new methodologies on the horizon, and discusses residual infectious risks associated with blood transfusion.     

140例成人人类免疫缺陷病毒感染与丙型肝炎病毒感染相互影响

目的 了解经输血或单采浆献血感染人类免疫缺陷病毒(HIV)的患者中丙型肝炎病毒(HCV)的感染率；分析HIV与HCV感染的相互影响。方法 对140例经输血或单采浆献血感染HIV的患者血清抗HCV、HBV—M、肝脏生化功能、CD4^ 和CD8^ 细胞计数、纤维胃镜、肝胆脾B超进行分析。结果 140例HIV感染和获得性免疫缺陷综合征(AIDS)患者中HCV抗体阳性者占91．5％(128／140)；HIV和HCV混合感染者肝功能损害较轻，与单纯HIV感染者比较，其肝功能、B超改变、CD4^ 细胞计数之间差异无统计学意义。结论 经输血或单采浆献血感染的HIV感染者中存在着极高的HCV感染(91．5％)。HIV和HCV混合感染者与单纯HIV感染者比较，肝功能损伤并不严重，提示HIV可能并不加速丙型肝炎的进展。     

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。     

HIV, hepatitis C and risk behaviour in a Canadian medium-security federal penitentiary. Queen's University HIV Prison Study Group

In a voluntary anonymous HIV and hepatitis C serology screen in a Canadian male medium security federal penitentiary, 68% of 520 prisoners volunteered a blood sample and 99% of those giving a blood sample completed a risk behaviour questionnaire which was linked numerically to the blood sample. Compared to previous screenings for HIV (4 years earlier), and hepatitis C (3 years earlier) in the same institution, HIV seroprevalence had risen from 1% to 2% and hepatitis C seroprevalence from 28% to 33%. The overwhelming risk association for hepatitis C was with drug use outside prison, although there was a small group of men who had only ever injected drugs inside prison, over half of whom had been infected with hepatitis C. The proportion of prisoners who had injected drugs in prison rose from 12% in 1995 to 24% in 1998. The proportion of surveyed individuals sharing injection equipment at some time in prison was 19%, and while HIV rates in the prison are currently low, HIV prevalence amongst Canadian street i.v. drug users is rising rapidly, underlining the need for urgent preventative measures in prisons.     

Impact of hepatitis B virus infection versus stage 3 HIV infection on serum lipids

The purpose of the study was to compare the impact of hepatitis B infection and Stage 3 (subclinical) HIV infection on serum lipids. The values of the serum lipid spectrum were studied in 30 patients with acute hepatitis B, 50 patients with Stage 3 IIIV infection, and 50 healthy individuals. The impact of hepatitis B virus infection and HIV infection on the serum lipid spectrum was ascertained to differ greatly. Just in Stage 3 (subclinical), with its history of less than 5 years, HIV injection causes more substantial lipid metabolic changes than moderate acute viral hepatitis.     

Prevalence of hepatitis C, hepatitis B, and human immunodeficiency virus in a Grand Rapids, Michigan emergency department

Objective: The objective of this study is to provide updated prevalence information on hepatitis C, hepatitis B, and human immunodeficiency virus (HIV) among patients in a high-volume emergency department (ED) located in a medium-sized, Midwestern city. Background: This study provides updated information regarding the prevalence of the blood-borne pathogens hepatitis C, hepatitis B, and HIV among ED patients. Prior studies of this type have focused on large inner-city populations with high incidence rates of blood-borne diseases. These studies have limited applicability to other common ED settings. Methods: A convenience sample of 404 patients was selected using blood previously drawn independent of the study. Patient-identifying information was unlinked from study results, which allowed waiver of informed consent from the Institutional Review Board. This blood was then tested for hepatitis C, hepatitis B, and HIV. Results: Prevalence of hepatitis C antibody was 4.0%, relative to the overall US population prevalence of 1.8%. Hepatitis B_sAg was present in 0.7% and HIV prevalence was 0.8%. There were no coinfections; therefore, there was a combined prevalence of blood-borne pathogens of 5.5%. Conclusions: The combined prevalence of blood-borne pathogens of 5.5% supports previous recommendations of universal precautions, particularly in settings where the overall prevalence may be underestimated.     

Therapy of hepatitis C in patients with HIV infection

Hepatitis C is found in approximately a third of patients infected with HIV. Therapy of hepatitis C in HIV patients is very important from several view points. First, hepatitis C in the setting of immunosuppression may progress faster, although recent data show that mortality from liver disease was decreased in highly active antiretroviral therapy. HIV/hepatitis C coinfection is associated with more frequent elevation in liver tests (drug-induced liver injury) during highly active antiretroviral therapy, and in some studies, hepatitis C has been associated with lower CD4+ recoveries. The therapeutic standard of care is a combination of peginterferon and ribavirin at a fixed dose, 800 mg/day, although higher ribavirin doses may further improve virologic outcomes. In patients that do not respond virologically, maintenance therapy with peginterferon monotherapy is a potential avenue to stem the advance of liver fibrosis, although controlled data in coinfected patients are needed to issue formal recommendations.     

艾滋病合并丙型肝炎的腹部超声表现

目的 探讨艾滋病（AIDS）患者合并丙型肝炎的腹部超声表现.方法 回顾性分析我院83例合并丙型肝炎的艾滋病患者（AIDS合并丙肝组）,以及106例单纯慢性丙型肝炎患者（单纯慢性丙肝组）的腹部超声表现,对比两组患者肝脏、脾脏和胆囊,以及腹腔淋巴结、腹水等异常的超声发现率.结果 肝脏肿大、肝内多发结节、脾肿大、脾内多发结节、胆囊壁增厚、腹腔淋巴结肿大、腹水等超声表现AIDS合并丙肝组发现率高于单纯慢性丙肝组,两组比较差异均有统计学意义（P〈0.01）;而肝内回声增粗的发生,AIDS合并丙肝组较单纯慢性丙肝组多,两组比较P〈0.05.结论 超声检查可以从形态学上反映艾滋病合并丙型肝炎引起腹部脏器的损害情况,对患者的早诊断、早治疗有重要意义.     

BLOOD DONORS AND BLOOD COLLECTION: Web interface–supported transmission risk assessment and cost‐effectiveness analysis of postdonation screening: a global model applied to Ghana,Thailand, and the Netherlands

BACKGROUND: The goal of our research was to actively involve decision makers in the economic assessment of screening strategies in their region. This study attempted to accomplish this by providing an easy‐to‐use Web interface at http://www.bloodsafety.info that allows decision makers to adapt this model to local conditions. STUDY DESIGN AND METHODS: The cost‐effectiveness was compared of 1) adding antigen screening to antibody screening for hepatitis C virus (HCV) and human immunodeficiency virus (HIV); 2) adding nucleic acid amplification testing (NAT) on hepatitis B virus (HBV), HCV, and HIV in minipool (pool of 6 [MP6] and 24 [MP24]) to antibody screening and hepatitis B surface antigen (HBsAg) screening; and 3) individual‐donation NAT on HBV, HCV, and HIV to antibody screening and HBsAg screening for Ghana, Thailand, and the Netherlands. RESULTS: The combination of HCV antibody‐antigen combination (combo) and HIV combo added to antibody screening in Ghana and Thailand was cost‐effective according to the WHO criteria. MP24‐NAT screening in Ghana was also cost‐effective. MP24‐NAT on HBV, HCV, and HIV was not cost‐effective compared to the other screening strategies evaluated for the Netherlands. Large regional differences in cost‐effectiveness were found for Thailand. CONCLUSION: The young transfusion recipient population of Ghana in combination with a high risk of viral transmission yields better cost‐effectiveness for additional tests. The advanced age of the transfused population of the Netherlands and a small risk of viral transmission gives poor cost‐effectiveness for more sensitive screening techniques. It was demonstrated that a global health economic model combined with a Web interface can provide easy access to risk assessment and cost‐effectiveness analysis.     

Pharmacokinetics of azidothymidine and its major metabolite glucuronylazidothymidine in hemophiliacs coinfected with human immunodeficiency virus and chronic hepatitis C

The increasingly reported cholestatic course of liver disease in hemophiliacs coinfected with human immunodeficiency virus (HIV) and hepatitis C (HCV) has been linked with impaired azidothymidine (AZT) metabolism in this patient group. Therefore, we compared the pharmacokinetics of AZT and its glucuronidated metabolite (glucuronylazidothymidine [GAZT]) in HIV/HCV-coinfected hemophiliacs without cirrhosis to HIV-infected patients without chronic hepatitis. Sixteen HIV/HCV-coinfected hemophiliacs without cirrhosis and six HIV-infected patients with negative hepatitis serology and normal liver transaminases received a single 100-mg oral dose of AZT. Subsequently, plasma concentrations of AZT and GAZT were measured during a 6-hour period by high-pressure liquid chromatography (HPLC). Blood samples were taken before and 30, 60, and 90 minutes and 2, 3, 6, and 8 hours after the intake of AZT. Pharmacokinetic parameters of AZT in HIV-infected patients with concomitant chronic hepatitis did not differ significantly as compared to patients without concomitant liver disease. GAZT half-life and mean residence time of GAZT, however, were significantly longer in HIV/HCV-coinfected hemophiliacs as compared to HIV-positive controls without hepatitis. In HIV-infected patients, underlying chronic hepatitis C does not require AZT dose adaptation. Yet despite normal oral clearance of AZT and GAZT, the increase of half-life and mean residence time of GAZT indicates a prolonged hepatic release of GAZT into the circulation of HIV-infected hemophiliacs with noncirrhotic hepatitis C.     

Management of advanced HIV disease in patients with tuberculosis or hepatitis co-infection

Advanced human immunodeficiency virus (HIV) disease can be defined as a cluster of differentiation 4 (CD4) count <50 cells/mm³ or the presence of an acquired immunodeficiency syndrome (AIDS)‐defining illness. In the UK and Ireland, the number of patients who present with advanced HIV disease is increasing, with 301/977 (31%) of patients presenting late (<200 CD4 cells/mm³). Many patients who present with advanced HIV disease will have comorbid conditions, such as hepatitis B or C or tuberculosis (TB), which complicates the choice of therapy. This article reviews the evidence and some clinical scenarios for specific patient groups who may present with advanced HIV disease: those with comorbid TB, hepatitis B or hepatitis C. The aim is to offer practical advice on therapeutic options for treatment‐naïve patients who present with advanced HIV disease on the basis of available clinical evidence.     

A preliminary analysis of the performance of a targeted HIV electronic medical records alert system: A single hospital experience

Early treatment of HIV relies on a timely detection of the infection, but many people living with HIV/AIDS are unaware of their infection. In the current study, we applied an electronic medical records (EMR)-based alert system flagging high-risk patients previously diagnosed with infections of syphilis, hepatitis A virus, hepatitis B virus, and/or hepatitis C virus, and those aged 20–50 years with a prior diagnosis of shingles. During the study period (April to October 2019), a total of 47 individuals among 22,264 patients visiting our department were identified as having high-risk of carrying HIV, and 14 of these individuals underwent HIV testing. Two males aged below 65 years with a previous diagnosis of syphilis were subsequently tested positive for HIV. This preliminary analysis of the EMR alert system facilitated the identification of high-risk people possibly carrying HIV, but the test rate remains to be improved.     

2010-2015年我国暗娼人群艾滋病病毒/梅毒/丙型病毒性肝炎感染状况分析

目的 了解我国2010-2015年暗娼人群艾滋病病毒（HIV）/梅毒/丙型病毒性肝炎（丙肝）抗体阳性率情况。方法 2010-2015年每年的4-6月,在全国艾滋病暗娼监测哨点开展连续横断面调查,通过匿名调查问卷收集调查对象基本人口学信息等,同时抽取静脉血进行HIV、梅毒和丙肝抗体检测,利用SPSS 18.0统计学软件进行数据整理和分析。结果 2010-2015年共监测暗娼1 180 926人,3种传染病抗体阳性率平均为HIV 0.25%（2 898/1 180 926）、梅毒2.54%（30 028/1 180 926）、丙肝0.72%（8 559/1 180 926）,逐年3种疾病抗体阳性率呈现下降趋势。不同人口学特征的暗娼人群感染情况不同,31岁年龄组、少数民族、外籍,文化程度为小学及以下、婚姻状态为离异或丧偶的暗娼人群HIV、梅毒和丙肝抗体阳性率均较高。场所来源为街头的暗娼人群,HIV/梅毒/丙肝抗体阳性率均高于其他场所来源的暗娼人群,差异有统计学意义,分别为HIV（2=2 807.11,P0.01）、梅毒（2=8 230.48,P0.01）、丙肝（2=778.30,P0.01）。多元logistic回归分析显示,吸毒（OR=17.82,95%CI:16.02~19.82）、初中及以下文化程度（OR=1.79,95% CI:1.58~2.03）、场所来源是街头/路边店（OR=2.74,95% CI:2.40~3.13）的暗娼感染HIV的风险较高。结论 我国暗娼人群整体梅毒抗体阳性率较高,31岁、文化程度较低和收入较低的街头低档暗娼HIV、梅毒和丙肝抗体阳性率均高于其他组暗娼人群。     

Hepatitis A and HIV: a clinical review of disease and strategies for prevention.

Hepatitis A, also known as infectious hepatitis, remains one of the more commonly transmitted types of viral hepatitis in the United States. Given the high prevalence of this illness, clinicians need to be aware not only about the clinical manifestations of this disease, but also about the special considerations that must be taken into account for persons coinfected with HIV. Antiretroviral management during acute hepatitis infection may be complicated by elevations of serum liver enzyme tests as well as by severe manifestations of associated symptoms such as nausea and vomiting. This article provides a brief overview of the clinical course of HIV infection and includes recommendations for antiretroviral medication management during acute illness. Additionally, strategies for prevention of disease are presented, with a focus on the efficacy and use of hepatitis A vaccines in persons with HIV.     

Chronic hepatitis C in patients with HIV/AIDS: a new challenge in antiviral therapy

HIV-infected patients are living longer since the introduction of highly active antiretroviral therapy. However, coinfection with the hepatitis C virus (HCV) leads to increased morbidity from liver disease and higher overall mortality. The prevalence of chronic hepatitis C among patients with HIV/AIDS ranges from 7% (sexual transmission of HIV) to >90% (injection drug use). Uncontrolled HIV infection seems to accelerate the progression of HCV-induced liver fibrosis. Forty-eight weeks of combination therapy with pegylated interferon alpha (2a or 2b) plus ribavirin achieves a sustained viral response in coinfected individuals in up to 38% with HCV genotype 1 and up to 73% with genotypes 2 or 3. The safety profile of this treatment is similar to therapy in HCV-monoinfected patients with influenza-like symptoms, cytopenia and neuropsychiatric symptoms dominating. However, HIV/HCV-coinfected patients who also take zidovudine develop more profound anaemia than those on other HIV nucleoside analogue therapy. Didanosine and stavudine are associated with rare but serious mitochondrial toxicity, such as pancreatitis or lactic acidosis. It does not appear that the addition of ribavirin increases that risk. There is currently no evidence that in HIV/HCV coinfection one pegylated interferon product is superior to the other. Contrary to common perception, it is also unproven that HIV/HCV-coinfected patients respond less well to therapy with peginterferon alpha plus ribavirin than HCV-monoinfected patients. Given the safety and efficacy of combination therapy with peginterferon plus ribavirin and the deleterious effects of chronic hepatitis C, all HIV/HCV-coinfected patients should be evaluated for therapy.     

Why are there different dynamics in the selection of drug resistance in HIV and hepatitis B and C viruses?

The arrival of new antiviral drugs to treat chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has given rise to great expectations along with concerns regarding the selection of drug-resistant variants. Many lessons learnt from HIV therapeutics can be helpful for designing adequate treatment strategies against viral hepatitis, the avoidance of sequential weak monotherapies being one of them. Although HIV, HBV and HCV share many biological features, including very rapid viral dynamics, distinctive characteristics explain why the speed of selection of drug resistance differs substantially between these viruses, being faster for HCV than for HIV and slower for HBV.