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）：估计全世界有 3600 万人感染 HIV，而超过 3 亿人感染 HBV。在HBV单一感染者中，HBe血清从乙型肝炎e抗原（HBeAg）阳性慢性肝炎状态转变为“非活动”或“携带者”状态（HBeAg阴性）历来被认为标志着HBV感染阶段的变化或阶段并导致更好的预后。经历自发 HBeAg 血清转换的患者可以减少肝纤维化，而“非活动携带者状态”患者的预后更佳，肝硬化和肝细胞癌 (HCC) 的发生率较低。 HBeAg 血清转化与更好结果的关联可能是由于它与 HBV 病毒载量减少有关，因为 HBV DNA 水平已被证明与 HCC 风险独立相关。与 HBV 单一感染相比，HIV-HBV 合并感染会增加肝脏相关死亡的风险。然而，关于 HIV-HBV 合并感染者的病毒学和血清学结果的信息很少。国家 HIV 指南建议开始 HIV 抗逆转录病毒治疗 (ART)，其中包括 2 种活性 HBV 药物，以防止对 HBV 产生耐药性。然而，一些专家认为，没有足够的数据来保证立即进行双重 HBV 治疗，并且如果单一疗法在 48-96 周后不能抑制 HBV，则对第二种 HBV 药物进行测序是合理的。此外，有限的数据表明，HIV-HBV 合并感染者实现 HBV 病毒抑制的可能性较小，也不太可能失去 HBeAg 并出现抗 HBe。艾滋病临床试验组 (ACTG) 纵向连锁随机试验 (ALLRT) 研究是一个由 4371 名 HIV 感染受试者组成的明确特征队列，这些受试者已前瞻性随机接受 ART 治疗，并将样本存储在中央存储库中。因此，我们建议在这个理想队列中识别那些患有活动性 HBV 感染的受试者，并作为我们的主要目标，比较接受 2 种 HBV 活性药物治疗的患者与接受 1 种 HBV 活性药物治疗的患者的 HBV 病毒学抑制时间和 HBeAg/抗 HBe 状态的变化。乙肝病毒活性剂的有效期超过 5 年。我们还将评估丁型肝炎合并感染、预后标志物的基因型，并对那些在治疗中从未抑制或反弹 HBV 病毒血症的患者进行耐药性检测。进一步描述 HIV-HBV 合并感染的病程将有助于开展未来的发病机制研究和治疗干预试验。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) 感染者发病和死亡的重要原因。与仅包含一种抗 HBV 活性药物的 HIV 疗法相比，用于治疗 HIV 和 HBV 的联合疗法的有效性数据有限。该提案将通过测量肝炎标志物和参与前瞻性、纵向随机 HIV 临床试验的 HIV-HBV 共感染患者储存的血液样本中乙型肝炎病毒的数量来检查 HBV 治疗的有效性。