长期包含TDF的ART和HIV-HBV合并感染中HBsAg丢失的进展率-功能性H

StephenW

Long-Term TDF-Inclusive ART and Progressive Rates of HBsAg Loss in HIV-HBV Coinfection-Lessons for Functional HBV Cure?
Jennifer Audsley  1 , Anchalee Avihingsanon, Margaret Littlejohn, Scott Bowden, Gail V Matthews, Christopher K Fairley, Sharon R Lewin, Joe Sasadeusz
Affiliations
Affiliation

    1
    aThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia; bDepartment of Infectious Diseases, The Alfred Hospital and Monash University, Melbourne, Australia; cHIV-NAT, Thai Red Cross AIDS Research Centre and Tuberculosis Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; dVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Doherty Institute, Melbourne, Australia; eThe Kirby Institute, Sydney, Australia; fDepartment of Infectious Diseases, St Vincent's Hospital, Sydney, Australia; gMelbourne Sexual Health Centre, Alfred Health, Melbourne, Australia; hCentral Clinical School, Faculty of Medicine, Monash University, Melbourne, Australia; and iVictorian Infectious Disease Service, Royal Melbourne Hospital, at the Doherty Institute, Melbourne, Australia.

    PMID: 32692112 DOI: 10.1097/QAI.0000000000002386

Abstract

Background: Tenofovir disoproxil fumarate (TDF) is effective in suppressing HIV and hepatitis B virus (HBV) replication in HIV-HBV coinfection although HBV DNA can persist in some individuals on TDF-containing antiretroviral therapy (ART). We initiated a prospective longitudinal study to determine durability of HBV virological control and clinical outcomes after prolonged TDF-based ART in HIV-HBV coinfection.

Methods: Ninety-two HIV-HBV coinfected participants on, or about to commence, TDF-containing ART from Australia (n = 41) and Thailand (n = 52) were enrolled. Participants were followed 6-monthly for 2 years, then annually to 5 years. Laboratory and clinical assessments and a serum sample were collected at each study visit. These analyses compare follow-up at 2 and 5 years.

Results: 12.0% (95% confidence interval 6.8 to 20.2) of total study entry cohort (n = 92) or 15.3% (95% confidence interval: 8.8 to 25.3) of those with data to year 5 (n = 72) lost hepatitis B surface antigen (HBsAg). The only statistically significant association with HBsAg loss was lower study entry quantitative HBsAg. CD4 T-cell count increased by a median 245 cells/mm3 between the preTDF sample and 5 years of follow-up. By year 5, 98.5% of the cohort had undetectable HBV DNA (<15 IU/mL) and 91.4% had undetectable HIV RNA (<20 copies/mL).

Conclusions: HBsAg loss was high and ongoing over 5 years of follow-up in HIV-HBV coinfected individuals on TDF-containing ART and undetectable HBV was almost universal. Although the pattern of HBsAg loss temporarily parallels immune reconstitution, we could not identify predictive immune markers. The high rate of HBsAg loss in HIV-HBV coinfection may offer valuable insights into the search for a functional HBV cure.

StephenW

长期包含TDF的ART和HIV-HBV合并感染中HBsAg丢失的进展率-功能性HBV治愈的经验？
珍妮弗·奥德斯利1，妮莎莉·阿维辛萨农，玛格丽特·利特尔约翰恩，斯科特·鲍登，盖尔·马修斯，克里斯托弗·费利，莎朗·雷文，乔·萨萨杜斯
隶属关系
联系

    1个
    a墨尔本大学彼得·多尔蒂感染与免疫研究所和澳大利亚墨尔本皇家墨尔本医院； b澳大利亚墨尔本阿尔弗雷德医院和莫纳什大学传染病科； cHIV-NAT，泰国曼谷朱拉隆功大学医学院泰国红十字会艾滋病研究中心和结核病研究室； d澳大利亚墨尔本多赫蒂研究所皇家墨尔本医院维多利亚传染病参考实验室； e澳大利亚悉尼的柯比研究所； f澳大利亚悉尼圣文森特医院传染病科； g澳大利亚墨尔本阿尔弗雷德健康中心墨尔本性健康中心； h澳大利亚墨尔本莫纳什大学医学院中央临床学院；以及澳大利亚墨尔本Doherty研究所皇家墨尔本医院的iVictorian传染病服务处。

    PMID：32692112 DOI：10.1097 / QAI.0000000000002386

抽象

背景：替诺福韦二富马酸富马酸盐（TDF）可有效抑制HIV-HBV合并感染中的HIV和乙型肝炎病毒（HBV）复制，尽管某些含有TDF的抗逆转录病毒疗法（ART）可使HBV DNA持续存在。我们开展了一项前瞻性纵向研究，以确定在HIV-HBV合并感染中基于TDF的ART延长后，HBV病毒学控制的持久性和临床结局。

方法：招募了来自或即将开始的来自澳大利亚（n = 41）和泰国（n = 52）的含TDF的ART的92名HIV-HBV合并感染的参与者。参与者每6个月追踪2年，然后每年追踪5年。每次研究访视时都要收集实验室和临床评估以及血清样本。这些分析比较了2年和5年的随访情况。

结果：共有5年肝炎数据丢失者（n = 72），占研究入组总数的12.0％（95％可信区间6.8至20.2）（n = 92）或15.3％（95％可信区间：8.8至25.3）。 B表面抗原（HBsAg）。与HBsAg丢失有关的唯一具有统计学意义的关联是较低的研究进入定量HBsAg。在preTDF样本和5年随访之间，CD4 T细胞计数平均增加了245细胞/ mm3。到第5年，该队列中98.5％的患者检测不到HBV DNA（<15 IU / mL），91.4％的患者检测不到HIV RNA（<20拷贝/ mL）。

结论：在含有TDF的ART上，HIV-HBV合并感染的个体中HBsAg的丢失率很高，并且持续了5年的随访，无法检测到的HBV几乎是普遍的。尽管HBsAg丢失的模式暂时与免疫重建平行，但我们无法确定预测性免疫标记。 HIV-HBV合并感染中HBsAg的高丢失率可能为寻找功能性HBV疗法提供有价值的见解。