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: 7860348
• 负责人: JUDITH Ann ABERG
• 金额: $ 16.9万
• 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/7860348
• 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; Recommendation; Regimen; Resistance; Retrospective Studies; Risk; Sampling; Serological; Simian B disease; Specific qualifier value; Staging; Tenofovir; Testing; Time; 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; randomized trial; 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（由申请人提供）：全球估计有3600万人感染了艾滋病毒，而超过3亿人患有HBV感染。在具有HBV一单感染的患者中，从历史上认为，从历史上考虑了抗原状态（HBEAG）抗原（HBEAG）阳性慢性肝炎的HBE血清转化，从历史上考虑到“无效”或“载体”状态（HBEAG阴性），以标志着HBV感染阶段或阶段的变化，并导致更好的预测。经历自发性HBEAG血清转化的患者可以减少肝纤维化和“非活性载体状态”患者的效果更高，肝硬化和肝细胞癌（HCC）的发生率较低。 HBEAG血清转化与更好的结果的关联可能是由于其与HBV病毒载荷的降低有关，因为HBV DNA水平已显示与HCC风险独立相关。与HBV单感染相比，HIV-HBV共感染会增加与肝相关死亡率的风险。但是，关于HIV-HBV共感染患者的病毒学和血清学结局的信息很少。国家HIV指南建议启动HIV抗逆转录病毒疗法（ART），其中包括2种活跃的HBV剂，以防止耐药性对HBV的耐药性。然而，一些专家认为，没有足够的数据来保证双重HBV治疗，并且如果单一疗法在48-96周后不能抑制HBV，则可以合理地对第二种HBV剂进行测序。此外，有限的数据表明，患有HIV-HBV共感染的人不太可能实现HBV病毒抑制，并且失去HBEAG并发展抗HBE的可能性较小。 AIDS临床试验组（ACTG）纵向连接的随机试验（ALLRT）研究是一项表征良好的4371名HIV感染受试者的队列，这些受试者被前瞻性随机分组以接收ART并在中央存储库中存储了样品。因此，我们建议在该理想队列中确定那些患有主动HBV感染的受试者，并且作为我们的主要目标，将HBV病毒学抑制的时间与HBEAG/抗HBE状态的变化相比，在接受2 HBV活性药物的人中，与在5年内获得HBV活性药物的人相比。我们还将评估肝炎共感染，预后标志物的基因型，并对那些从未抑制或没有抑制HBV病毒血症的人进行耐药性测试。进一步表征HIV-HBV共感染的疾病过程将有助于开发未来的发病机理研究和治疗介入试验。公共卫生相关性：乙型肝炎病毒（HBV）感染是人类免疫缺陷病毒（HIV）感染患者的发病率和死亡的重要原因。与仅包含一种针对HBV的活性药物的HIV疗法相比，用于治疗HIV和HBV的组合疗法有效性的数据有限。该提案将通过测量肝炎标志物和HIV-HBV共同感染的患者储存的血液样本中肝炎病毒的量来检查HBV治疗的有效性，这些患者参加了前瞻性，纵向随机HIV临床试验。