人类免疫缺陷病毒/丙型肝炎病毒混合感染者抗丙型肝炎病毒治疗的进展

由于人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）有相同的传播途径,HIV/HCV混合感染现象十分普遍,已成为严重的公共卫生问题。高效抗逆转录病毒治疗（HAART）的应用显著减少了与HIV感染相关的发病率和病死率,而HCV混合感染引起的慢性肝脏疾病日益成为HIV/HCV混合感染者发病和死亡的重要因素。HIV/HCV混合感染者HCV相关肝病的风险增加,有效的抗HCV治疗对延长这一人群的生存期至关重要。本文就抗HCV治疗对象的评估、治疗时机的选择、治疗的方法、治疗监测和疗效评估以及治疗注意的问题作一综述。     

Hepatitis C virus in the setting of HIV or hepatitis B virus coinfection

Because of shared routes of transmission, coinfection with hepatitis C virus (HCV) or hepatitis B virus (HBV), or both, is common among HIV-infected persons, affecting approximately 15 to 30% and 10 to 15% of patients, respectively. Advances in antiretroviral therapy have improved the life expectancy of patients infected with HIV, and, as a consequence, HCV-related liver disease has emerged as a significant comorbid disease among such patients. Concurrent HIV infection may be associated with higher serum HCV RNA levels, accelerated progression of hepatic fibrosis, increased risk of end-stage liver disease, hepatocellular carcinoma and death among persons coinfected with hepatitis C. Similarly, coinfection with HCV and HBV may lead to more severe liver disease and greater risk of hepatocellular carcinoma (HCC) than does HCV infection alone. Although definitive randomized controlled trials are not yet completed, current guidelines recommend the use of pegylated interferon alfa plus ribavirin for the treatment of chronic HCV in eligible HIV-infected persons. Conversely, the optimal treatment of chronic HCV in persons with chronic HBV infection has not been defined but may include pegylated interferon alfa plus ribavirin, with or without additional antiviral agents, such as lamivudine or adefovir, or both.     

Management of hepatitis C in HIV-infected patients

As the survival of HIV-infected patients has been lengthening over the past 10 years as a consequence of effective antiretroviral therapy, hepatitis C virus (HCV) coinfection has emerged as a major cause of morbidity and mortality in this population. HCV/HIV coinfection is associated with accelerated progression of liver disease, untoward effects on the immunologic and virologic response to antiretroviral medications, and possibly with a more aggressive course of HIV disease. The results of major trials of combination therapy for HCV in coinfected patients have clearly established the combination of pegylated interferon-α with ribavirin as the treatment of choice in this population. However, the effectiveness and tolerability of this regimen remains suboptimal, particularly in patients with genotype 1 HCV infection. This paper reviews the impact of HCV coinfection in HIV-infected patients, outlines current concepts on management and antiviral treatment, and discusses some of the newer agents, currently in the therapeutic pipeline, that are directed against novel molecular targets.     

重视HIV合并HCV感染的诊断和治疗

HIV和HCV的传播途径相同,二者合并感染相当常见。高效抗反转录病毒治疗的广泛应用显著降低了HIV感染相关疾病的发病率和病死率,但HCV感染引起的终末期肝病已成为HIV/HCV合并感染者死亡的重要原因。因此,加强HIV合并HCV感染者的诊断和治疗对于降低HIV感染的病死率十分重要。本文就HIV合并HCV感染者病毒的相互影响、诊断和治疗进行概述。     

HIV coinfection with hepatitis C virus: evolving epidemiology and treatment paradigms

Chronic hepatitis C virus (HCV) infection has become a major threat to the survival of human immunodeficiency virus (HIV)-infected persons in areas where antiretroviral therapy is available. In coinfection, viral eradication has been difficult to attain, and HCV therapy is underused. Novel therapies may be particularly beneficial for this population, yet studies lag behind those for HCV monoinfection. Increasingly, incident HCV among HIV-infected men who have sex with men is associated with sexual risk behavior further research should be performed to refine understanding of the causal mechanism of this association. The phenomenon of aggressive hepatic fibrogenesis when HIV infection precedes HCV acquisition requires longer-term observation to ensure optimal timing of HCV therapy. Medical management in coinfection will be improved by enhancing HCV detection, with annual serologic testing, screening with HCV RNA to detect acute infection, and HIV testing of HCV-infected individuals; by addressing HCV earlier in coinfected persons; and by universal consideration for HCV therapy. HCV drug trials in individuals coinfected with HIV should be expedited. HIV/HCV coinfection remains a growing and evolving epidemic; new developments in therapeutics and improved care models offer promise.     

Hepatitis C virus/human immunodeficiency virus coinfection: clinical management issues.

The use of highly active antiretroviral therapy (HAART) has extended the healthy lifespan of patients infected with human immunodeficiency virus (HIV); deaths among people with AIDS declined for the first time in 1996, after the institution of this therapeutic approach. As the life expectancy of HIV-infected patients increases, greater attention will need to be focused on the recognition and management of potentially severe concurrent illnesses that may increase their mid- to long-range morbidity and mortality. The incidence of infection by hepatitis C virus (HCV) is increased among patients with HIV disease, reflecting shared epidemiological risks. HCV not only may have an impact on the health status of HIV-infected patients but also may decrease their quality of life and increase their health care costs. Although clinicians have been reluctant to treat viral hepatitis C in the HIV-infected population, this therapeutic nihilism is unwarranted. The majority of studies have concluded that treatment of hepatitis C in HIV-infected patients results in an initial efficacy and long-term response similar to those in the HIV-seronegative population. Furthermore, treatment of HCV infection in HCV/HIV-coinfected patients may improve tolerance for antiretroviral medications. Physicians caring for patients with HIV infection require up-to-date information to make rational decisions regarding HCV coinfection to ensure that morbidity and mortality are minimized and that quality of life and medical care costs are optimized.     

Management of hepatic complications in HIV-infected persons

In the era of effective antiretroviral therapy (ART), liver disease is the second most common cause of death among persons with human immunodeficiency virus (HIV) infection. Liver disease-related deaths mostly result from chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). In addition, recent reports suggest that HCV infection may be transmitted sexually between HIV-infected men who have sex with men. Management of these conditions in HIV-infected persons requires careful consideration, balancing the potential benefits of therapy with the potential for significant treatment-related adverse effects (HCV infection) and viral resistance and/or hepatitis flares (HBV infection). Furthermore, several antiretroviral agents are active against HBV infection, including lamivudine, emtricitabine, tenofovir, and, more recently, entecavir. Despite the complexity and potential for antiretroviral-associated hepatotoxicity, ART usually is safe for patients with viral hepatitis coinfection, and, in some cases, treatment for HIV infection may be beneficial for the liver.     

Hepatitis C virus-human immunodeficiency virus coinfection

As a result of shared modes of transmission, chronic hepatitis C infection is common in HIV-infected patients, particularly among those who have used injection drugs as well as men who have sex with men (MSMs). In the era of effective antiretroviral therapy, HCV infection has emerged as a major cause of morbidity and mortality worldwide. Over the last decade, treatment with peginterferon (PEG-IFN) plus ribavirin (RBV) has been recommended for coinfected patients who are at the greatest risk for liver disease; however, the effectiveness of HCV treatment in this population has been disappointing. Challenges to the use of HCV NS3/4A protease inhibitors, telaprevir and boceprevir, patients with HIV/HCV coinfection include the potential for interactions between different drugs, addition of drug toxicities, and the need for therapy with PEG-IFN. Despite these challenges, limited data indicate that telaprevir and boceprevir given in combination with PEG-IFN/RBV increase the rate of viral suppression in coinfected patients with manageable toxicity and drug-drug interaction profile. Accordingly, these agents may be recommended for HCV treatment in carefully selected HIV-infected persons.     

Challenges in the HIV patient coinfected with hepatitis C

Hepatitis C infection (HCV) in HIV-infected individuals is prevalent. HCV-mediated hepatic disease is clearly exacerbated in the setting of HIV disease and is of increasing concern as coinfected patients live longer on highly active antiretroviral therapy (HAART). Treatment for HCV in the setting of HIV coinfection is rapidly evolving. Complex treatment issues arise in patients requiring the multiple antiviral therapies that target HCV and HIV. This review focuses on the major issues involved in the pathogenesis and treatment of coinfected patients in the era of HAART.     

HIV And HCV infection among opiate-dependent patients and methadone doses: the PROTEUS study

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are prevalent infections in opiate-dependent patients. Opiate replacement treatment (ORT) with methadone or buprenorphine is associated with several important outcomes among patients with opiate dependence. However, little is known about outcomes in patients with HIV and/or HCV infections that are in ORT. Also, it is not well established whether the presence of HCV or HIV infection could be associated with higher methadone doses. This paper reanalyzes the database of PROTEUS study, using two principal variables: methadone dose and presence of HIV and/or HCV infection. PROTEUS recruited 621 patients (84.1% were male, mean age: 38.9 years, SD: 7.9), information about the presence of HIV in status was available for 390 patients. Of those, 134 (34.4%) were HIV-infected. Whilst, information about HCV infection was available for 377 patients. Of those, 315 (83.6%) were HCV-infected. Information on HIV/HCV coinfection was available for 376 patients, of those, 112 (29.8%) had this coinfection. HIV-infected and HIV/HCV-coinfected patients received higher methadone doses than those without these infections. Antiretroviral therapy (ART) was used in 80% of patients with HIV infection. The proportion of patients taking antiretroviral drugs was significantly higher for patients treated with higher methadone doses (p?相似文献   

HIV and coinfected patients

HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) infections are major public health problems. Patients at risk for HIV infection are likely also at risk for HCV and HBV because of shared routes of transmission. HIV and antiretroviral therapy (ART) have a significant impact on HCV and HBV. HIV coinfection accelerates HCV and HBV natural history, leading to an increased incidence of cirrhosis, development of hepatocellular carcinoma (HCC), and death. Universal screening for HCV and HBV infections in HIV-infected patients is essential. Proper screening combined with up-to-date treatment strategies can prevent these complications. This review focuses on important aspects and recent developments in the rapidly evolving field of coinfection.     

Treatment of chronic hepatitis C in human immunodeficiency virus/hepatitis C virus-coinfected patients in the era of pegylated interferon and ribavirin

A significant percentage of human immunodeficiency virus (HIV) -infected individuals are also infected with the hepatitis C virus (HCV). With the much-improved survival of HIV-infected patients through the use of highly active antiretroviral therapy, liver disease caused by coinfection with HCV has emerged as a significant threat to the health and survival of persons with HIV disease. HIV/HCV-coinfected patients with ongoing HIV viremia have a faster rate of HCV-related liver fibrosis progression and a more rapid progression to liver failure or hepatocellular carcinoma than HCV-monoinfected persons. In contrast to the deleterious effect of HIV on HCV-related liver disease, most studies have shown that HCV does not influence progression of HIV infection to AIDS or death. HCV therapy with peginterferon alfa (2a or 2b) plus ribavirin can achieve a sustained viral response in HIV/HCV-coinfected patients of up to 38% in HCV genotype 1 and up to 73% in genotypes 2 and 3. The safety profile is largely similar to therapy in HIV-monoinfected patients, but there is a higher incidence of mitochondrial toxicity in patients taking didanosine or stavudine and of anemia in patients taking zidovudine. There is no proven anti-HCV therapy for HIV/HCV-coinfected patients with end-stage liver disease (ESLD). Liver transplantation is being investigated as a potential therapeutic option for HIV-infected individuals with ESLD, and initial reports are encouraging. Given that pegylated interferon and ribavirin have been shown to be safe and effective for HIV/HCV coinfection as well as HCV monoinfection, all HIV/HCV-coinfected patients should be evaluated for therapy.     

Gammadelta T cell activation by chronic HIV infection may contribute to intrahepatic vdelta1 compartmentalization and hepatitis C virus disease progression independent of highly active antiretroviral therapy

HIV and hepatis C virus (HCV) coinfection is frequently associated with rapid progression of HCV-related disease, resulting in a higher risk of cirrhosis. Data suggest that natural T cells expressing the Vdelta1 T cell receptor rearrangement are recruited in the liver of chronically HCV-infected patients and are increased in the peripheral blood of HIV-infected persons. We studied gammadelta T cell distribution in the peripheral blood and liver of HCV-infected and HIV/HCV-coinfected patients in the presence and absence of antiretroviral therapy. We observed that Vdelta1+ T cells releasing helper T cell type 1 cytokines are compartmentalized not only in the liver of HCV+ patients, but also of HIV/HCV-coinfected persons. HIV/HCV patients showed an increased frequency of both peripheral and intrahepatic Vdelta1 natural T lymphocytes, resulting in a higher degree of hepatic inflammation when compared with patients with other liver diseases. Finally, highly active antiretroviral therapy (HAART) was unable to restore Vdelta1T cell circulation to normal levels in chronically HIV-infected persons. We conclude that gammadelta T lymphocytes released from tissue to the bloodstream circulation under the influence of chronic HIV infection may contribute to intrahepatic Vdelta1 compartmentalization and progression of liver disease, independently of HAART.     

Pathogenesis of HIV-HCV coinfection

Hepatitis C virus (HCV) and HIV-1 are often harbored in the same host, establishing chronic infections typically characterized by persistent viremia. HIV-1 has deleterious effects on the course of HCV infection by increasing the rate of HCV viral persistence, quantitative HCV RNA levels, and ultimately the liver fibrosis progression rate. Conversely, HCV may blunt the effectiveness of immune reconstitution following antiretroviral therapy in HIV-infected individuals. Better understanding of the pathogenic mechanisms underlying these clinical observations may facilitate novel and effective therapeutic interventions that tackle the clinical conundrums raised by HIV/HCV coinfection.     

European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV-infected adults

OBJECTIVES: With the decline in HIV-associated morbidity and mortality following the introduction of highly active antiretroviral therapy (HAART), liver disease has emerged as a major cause of death in HIV/hepatitis B virus (HBV) and HIV/hepatitis C virus (HCV) coinfected persons. Therefore, screening for underlying viral hepatitis coinfection and the provision of management and treatment recommendations for patients with chronic viral hepatitis are of great importance in preventing, as far as possible, the development of liver disease. With the introduction of new agents for the treatment of hepatitis B and increased knowledge of how best to manage hepatitis C, an update of current guidelines for management of HBV and HCV coinfection with HIV is warranted. SUMMARY: Clearly, all HIV-infected patients should be screened for hepatitis A, B and C, taking into account shared pathways of transmission. Patients who are seronegative for hepatitis A and B should be considered for vaccination. In HIV-infected patients with chronic hepatitis B, the first important differentiation is whether HAART is required or not. In the setting of stable HIV infection, with no need for HAART, several treatment options are available, namely treatment with interferon, early initiation of HAART, or selective non-HIV active anti-HBV nucleoside therapy, with the aim of achieving undetectable HBV DNA levels. In most cases, undetectable HBV DNA can only be achieved with combination therapy. With regard to hepatitis C, individualized tailoring of the duration of HCV therapy is advisable, taking into account rapid or delayed virological response. In patients who do not achieve at least a 2 log drop in HCV RNA at week 12, treatment can be terminated because of the low probability of achieving sustained virological response. Overall, with the currently available treatment algorithms, HCV can be eradicated in over 50% of patients. Therefore, HCV therapy should be considered and discussed with the patient if an indication for HCV therapy (elevated liver enzymes, positive HCV RNA and >F1 fibrosis) is present. CONCLUSIONS: Management of underlying hepatitis B and/or C in patients with HIV infection is of great importance in preventing liver disease-associated morbidity and mortality.     

Alcohol use and HIV pharmacotherapy

Alcohol consumption by individuals infected with HIV is an important medical management issue with significant implications for the effectiveness of antiretroviral therapy as well as an important evolving field of HIV research. Alcohol consumption is a risk factor for poor medication adherence and can modify liver drug metabolism, both of which can lead to the emergence of drug-resistant virus. Research indicates that alcohol consumption greater than 50 g/day (four or five drinks) is a risk factor for liver disease progression among patients with HIV/HCV coinfection. In addition, alcohol-induced cirrhosis can result in changes in drug metabolism in the liver through compromised liver function. More research studies are needed to elucidate the biological and molecular basis of the clinical changes induced by alcohol consumption in HIV-infected individuals and on the relationship of these changes to the effectiveness of HIV pharmacotherapy. Specifically, research areas that are of particular importance are (1) determining alcohol consumption levels and patterns and its impact on antiretroviral medication adherence, efficacy, and physician prescribing practices; (2) identifying behavioral interventions to enhance adherence to HIV medications and reduce alcohol consumption; (3) clarifying the relationships and interactions among alcohol metabolism, HIV drug metabolism, and pharmacogenetics; (4) elucidating the extent of liver toxicity due to antiretroviral therapy and drug-drug interactions in individuals who consume alcohol; and (5) delineating the contribution of alcohol consumption to end-stage organ damage, particularly in HIV/HCV coinfection.     

Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review

Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients.     

Executive summary of the GeSIDA consensus document on control and monitoring of HIV-infected patients

The continuous increase in our knowledge of HIV medicine and antiretroviral treatment has led us to draft specific consensus documents focused on topics other than antiretroviral therapy, such as treatment of opportunistic diseases, pre- and post-exposure prophylaxis, metabolic abnormalities, treatment of HBV or HCV coinfection, treatment of patients coinfected with tuberculosis, osteoporosis, kidney disorders, and cardiovascular risk. Accordingly, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology has promoted the drafting of this consensus document on the control and monitoring of adult patients infected with HIV. The document provides recommendations on the initial evaluation and subsequent monitoring of HIV-infected patients that will prove useful for all professionals involved in the management of this infection.     

HIV AND HCV COINFECTION: PREVALENCE,ASSOCIATED FACTORS AND GENOTYPE CHARACTERIZATION IN THE MIDWEST REGION OF BRAZIL

A cross-sectional study on prevalence, associated factors and genotype distribution of HCV infection was conducted among 848 HIV-infected patients recruited at reference centers in the Midwest Region of Brazil. The prevalence rate of HIV-HCV coinfection was 6.9% (95% CI: 5.2 to 8.6). In multivariable analysis, increasing age, use of illicit drugs (injection and non-injection), a history of blood transfusion before 1994, and the absence of a steady partnership were significant independent associated factors for HIV-HCV coinfection. The phylogenetic analysis based on the NS5B region revealed the presence of two major circulating genotypes of HCV: genotypes 1 (58.3%) and 3 (41.7%). The prevalence of HIV-HCV coinfection was lower than those reported in studies conducted with HIV-infected patients in different regions of Brazil, due to the fact that illicit drug use is not a frequent mode of HIV transmission in this region of Brazil. Serologic screening of HIV-patients for HCV before initiating antiretroviral treatment, a comprehensive identification of associated factors, and the implementation of effective harm reduction programs are highly recommended to provide useful information for treatment and to prevent HCV coinfection in these patients.     

Hepatitis B and C virus coinfection in The TREAT Asia HIV Observational Database

BACKGROUND AND AIM: Most studies of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection with HIV have been conducted among Western patient populations. This study aims to assess rates of HBV and HCV coinfection, and their impact on response to antiretroviral therapy and mortality, using data from The TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of patients with HIV in the Asia-Pacific region. METHODS: Patients who had been tested either HBV surface antigen (HBsAg) or HCV antibody were included. Patients who ever tested positive for HBV or HCV were regarded as coinfected for the duration of the study. RESULTS: Results of hepatitis tests were available for 55% (HBV) and 49% (HCV) of 2979 TAHOD patients, with prevalence of HBV and HCV coinfection both at approximately 10%. Mean CD4 change at 180 days after antiretroviral treatment initiation was 118.8 cells/muL and patients with either HBV or HCV had a lower but non-significant CD4 increase compared with patients with HIV only. Median time to reach undetectable viral load (<400 copies/mL) was 148 days and was not independently associated with HBV or HCV. In univariate analysis, patients with HCV had increased mortality (unadjusted hazard ratio, HR 2.80, P = 0.007). However, neither HBV (adjusted HR 0.80, 95% confidence interval CI 0.24-2.64, P = 0.710) nor HCV (adjusted HR 1.06, 95% CI 0.40-2.79, P = 0.905) was associated with increased mortality after adjustment for other covariates. Both HBV and HCV remained independently associated with elevated alanine aminotransferase (ALT) in the multivariate model (HBV, adjusted HR 1.94, 95% CI 1.04-3.62, P = 0.037; HCV, adjusted HR 2.74, 95% CI 1.47-5.12, P = 0.002). CONCLUSION: The impact of hepatitis coinfection on immunological and virological responses to antiretroviral therapy and HIV disease progression among this Asian cohort are similar to that seen in Western countries. The longer-term impact of hepatitis coinfection on both HIV disease and liver disease morbidity and mortality needs to be monitored.