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

描述（由申请人提供）：全球估计有3600万人感染HIV，而超过3亿人感染HBV。在HBV单一感染者中，HBe从B e抗原（HBeAg）阳性慢性肝炎状态到“非活动”或“携带者”状态（HBeAg阴性）的血清转换历来被认为标志着HBV感染阶段或阶段的变化，并导致更好的预后。发生自发性HBeAg血清转换的患者可以减少肝纤维化，而“非活动性携带状态”患者的预后更好，肝硬化和肝细胞癌（HCC）的发生率更低。HBeAg血清转换与更好的结局相关可能是由于其与HBV病毒载量降低相关，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合并感染增加了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。国家艾滋病指南建议启动艾滋病抗逆转录病毒治疗（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，如果单药治疗在48-96周后不能抑制HBV，那么第二种HBV药物是合理的。此外，有限的数据表明，HIV-HBV合并感染的人不太可能实现HBV病毒抑制，也不太可能丢失HBeAg并产生抗-HBe。艾滋病临床试验组（ACTG）纵向连锁随机试验（ALLRT）研究是一项充分表征的队列研究，包括4371例HIV感染受试者，这些受试者前瞻性随机接受ART，并将样本储存在中央储存库。因此，我们建议在该理想队列中确定活动性HBV感染的受试者，并将接受2种HBV活性药物的受试者与接受1种HBV活性药物的受试者在5年内至HBV病毒学抑制的时间和HBeAg/抗- HBe状态的变化进行比较，作为我们的主要目的。我们还将评估丁型肝炎合并感染，预后标志物的基因型，并对那些从未抑制或在治疗中有反弹的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未来发病机制研究和治疗干预试验的发展。公共卫生相关性：B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。与仅含一种抗HBV活性药物的HIV治疗相比，用于治疗HIV和HBV的联合治疗的有效性数据有限。该提案将通过测量参加前瞻性、纵向随机HIV临床试验的HIV-HBV合并感染患者的储存血液样本中的肝炎标志物和B型肝炎病毒量来检查HBV治疗的有效性。

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.