Virologic and Serologic Outcomes of Persons with HIV and HBV co-infection on Mono

HIV 和 HBV 混合感染者的病毒学和血清学结果

• 批准号: 7684377
• 负责人: JUDITH Ann ABERG
• 金额: $ 29.6万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-05 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7684377
• 关键词: AIDS clinical trial group; Anti-Retroviral Agents; Antibodies; Antiretroviral drug resistance; Antiviral Agents; Antiviral Therapy; Blood specimen; Carrier State; Chronic Hepatitis; Cirrhosis; Clinical Trials; Combined Modality Therapy; Data; Development; Disease; Disease Progression; Drug resistance; Effectiveness; Expert Opinion; Exposure to; Failure; Future; Genotype; Guidelines; Hepatitis; Hepatitis B; Hepatitis B Virus; Hepatitis B e Antigens; Hepatitis C virus; Hepatitis D; Human; Immunologic Deficiency Syndromes; Incidence; Infection; Kinetics; Lamivudine; Learning; Link; Liver; Liver Fibrosis; Measures; Mono-S; Morbidity - disease rate; Mutation; Opportunistic Infections; Outcome; Pathogenesis; Patients; Persons; Pharmaceutical Preparations; Phase; Primary carcinoma of the liver cells; Prognostic Marker; Publishing; Randomized; Randomized Controlled Clinical Trials; Recommendation; Resistance; Retrospective Studies; Risk; Sampling; Serological; Simian B disease; Specific qualifier value; Staging; Tenofovir; Testing; Time; Treatment Protocols; United States Dept. of Health and Human Services; Viral; Viral Drug Resistance; Viral Load result; Viremia; Virus Diseases; anti-hepatitis B; antiretroviral therapy; base; clinically relevant; cohort; drug development; emtricitabine; experience; follow-up; mortality; outcome forecast; prevent; prospective; public health relevance; repository; resistance mutation; response; treatment strategy; viral DNA

DESCRIPTION (provided by applicant): An estimated 36 million people worldwide have HIV infection, while over 300 million have HBV infection. Among those with HBV mono-infection, HBe seroconversion from the state of Hepatitis B e antigen (HBeAg) positive chronic hepatitis to an "inactive" or "carrier" state (HBeAg negative) has historically been considered to mark a change in HBV infection phase or stage and results in a better prognosis. Patients who experience spontaneous HBeAg seroconversion can have reduction in hepatic fibrosis and "inactive carrier status" patients have more favorable outcomes, with lower incidence of cirrhosis and hepatocellular carcinoma (HCC). The association of HBeAg seroconversion with better outcome may be due to its association with reduction in HBV viral load as HBV DNA level has been shown to be independently associated with risk of HCC. When compared with HBV mono-infection, HIV-HBV co-infection increases risk of liver-related mortality. However there is little information on the virologic and serologic outcomes of those with HIV-HBV coinfection. National HIV guidelines recommend the initiation of HIV antiretroviral therapy (ART) that includes 2 active HBV agents in order to prevent development of drug resistance to HBV. Yet some experts argue that there is insufficient data to warrant dual HBV therapy immediately and that it is reasonable to sequence a second HBV agent if monotherapy does not suppress HBV after 48-96 weeks. Furthermore, limited data suggest that persons with HIV-HBV coinfection are less likely to achieve HBV viral suppression and less likely to lose HBeAg and develop anti-HBe. The AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study is a well characterized cohort of 4371 HIV-infected subjects who have been prospectively randomized to receive ART and have stored samples at a central repository. We therefore propose to identify those subjects with active HBV infection among this ideal cohort and as our primary objective compare the time to HBV virologic suppression and change in HBeAg/anti- HBe status among those who receive 2 HBV active agents compared with those who receive one HBV active agent over a 5 year period. We will also evaluate for Hepatitis D co-infection, genotype for markers of prognosis and perform resistance testing on those who never suppress or have rebound HBV viremia on therapy. Further characterizing the disease course of HIV-HBV coinfection will assist in development of future pathogenesis studies and treatment interventional trials. PUBLIC HEALTH RELEVANCE: Hepatitis B Virus (HBV) infection is a significant cause of morbidity and mortality among those with Human Immunodeficiency Viral (HIV) infection. There is limited data on the effectiveness of combination therapies used to treat both HIV and HBV compared with HIV therapies that contain only one active drug against HBV. This proposal will examine the effectiveness of HBV treatment by measuring hepatitis markers and the amount of Hepatitis B virus in stored blood samples from HIV-HBV coinfected patients who participated in prospective, longitudinal randomized HIV clinical trials.

描述(申请人提供)：据估计，全世界有3600万人感染艾滋病毒，而超过3亿人感染乙肝病毒。在HBV单感染者中，HBe血清学转换从HBe抗原(HBeAg)阳性的慢性肝炎状态转变为“非活动性”或“携带者”状态(HBeAg阴性)历来被认为是标志着乙肝病毒感染阶段或阶段的改变，并导致更好的预后。自发性HBeAg血清转换的患者肝纤维化程度减轻，“非活动性携带者状态”患者预后较好，肝硬变和肝细胞癌的发生率较低。HBeAg血清转换与较好的预后相关，可能是因为它与乙肝病毒载量的降低有关，因为HBVDNA水平已被证明与肝细胞癌的风险独立相关。与单一感染乙肝病毒相比，艾滋病病毒和乙肝病毒混合感染增加了肝脏相关死亡的风险。然而，关于艾滋病毒-乙肝病毒混合感染者的病毒学和血清学结果的信息很少。国家艾滋病毒指南建议启动艾滋病毒抗逆转录病毒疗法(ART)，其中包括两种活性的乙肝病毒制剂，以防止对乙肝病毒产生抗药性。然而，一些专家认为，没有足够的数据证明立即进行双重乙肝治疗是合理的，如果单一疗法在48-96周后不能抑制乙肝病毒，那么对第二种乙肝药物进行排序是合理的。此外，有限的数据表明，艾滋病毒-乙肝病毒混合感染者不太可能实现乙肝病毒抑制，也不太可能失去HBeAg和发展抗-HBe。艾滋病临床试验组织(ACTG)纵向链接随机试验(ALLRT)研究是一项具有良好特征的队列研究，包括4371名艾滋病毒感染者，他们被前瞻性地随机分配接受抗逆转录病毒治疗，并将样本存储在中央储存库。因此，我们建议将活动性乙肝病毒感染的受试者确定在这个理想的队列中，作为我们的主要目标，比较接受2种乙肝病毒活化剂的患者与接受1种乙肝病毒活化剂的患者在5年内的乙肝病毒抑制时间和HBeAg/抗-HBe状态的变化。我们还将评估丁型肝炎合并感染、预后标志的基因分型，并对那些在治疗中从未抑制或有反跳性乙肝病毒血症的患者进行耐药性测试。进一步明确HIV-HBV二联感染的病程特征，将有助于今后的发病机制研究和治疗干预试验的开展。公共卫生相关性：在人类免疫缺陷病毒(HIV)感染者中，乙肝病毒(HBV)感染是发病率和死亡率的重要原因。与只含有一种抗乙肝活性药物的艾滋病毒疗法相比，用于治疗艾滋病毒和乙肝病毒的联合疗法的有效性的数据有限。这项建议将通过测量参加前瞻性、纵向随机艾滋病毒临床试验的艾滋病毒-乙肝混合感染患者的储存血液样本中的肝炎标志物和乙肝病毒数量来检验乙肝治疗的有效性。