在HIV与慢性乙肝病毒合并感染情况下开始抗逆转录病毒治疗（ART）后乙肝表面抗原（HBsAg）消失的动力学及预测因素

Kinetics and predictors of Hepatitis B surface antigen (HBsAg) loss after commencing HBV-active antiretroviral therapy (ART) in the setting of HIV-and chronic HBV co-infection.

作者信息

Audsley Jennifer, Avihingsanon Anchalee, Li Xin, Edwards Rosalind, Jackson Kathy, Warner Nadia, Maslac Olivia, Revill Peter, Lwin Hay Mar Su, Gatechompol Sivaporn, Kumarasamy Nagalingeswaran, Spelman Tim, Azwa Iskandar, Kamarulzaman Adeeba, Lewin Sharon R, Sasadeusz Joe

机构信息

Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne Australia.

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, and Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

出版信息

Clin Infect Dis. 2025 May 31. doi: 10.1093/cid/ciaf281.

DOI:10.1093/cid/ciaf281

PMID:40447285

Abstract

BACKGROUND

An effective therapeutic strategy for HBV cure remains an urgent unmet need. We aimed to define the incidence, kinetics and predictors of hepatitis B surface antigen (HBsAg) loss in people living with HIV and HBV (PLWH-HBV) following HBV-active antiretroviral therapy (ART) in PLWH-HBV in Asia.

METHOD

97 PLWH-HBV commencing HBV-active ART were recruited prospectively in Thailand (n=94) and Malaysia (n=3) then followed for 24 months. Time to HBV serology change was calculated. Univariate associations between baseline characteristics and HBsAg loss were examined using the Mann-Whitney or Chi-square tests. Multivariable analysis was undertaken using Cox regression.

RESULTS

21 individuals (22%) lost HBsAg during follow-up (11.7 per 100 PY), 14 of whom gained anti-HBs. 22/61 (36.1%) individuals who were hepatitis B "e" antigen (HBeAg) positive at baseline lost HBeAg over the study, 15 of whom gained anti-HBe. Most individuals lost HBsAg and HBeAg by the month 12 study visit (81% and 63.6%, respectively), with median times of 5.8 and 12.0 months to HBsAg and HBeAg loss, respectively. Univariate analysis showed baseline characteristics associated with HBsAg loss were higher alanine aminotransferase (ALT, p=0.005), tenofovir alafenamide (TAF)-containing ART regimen (p=0.025), younger age (p=0.040), lower liver stiffness (p=0.010) and quantitative HBsAg< log102.0 IU/ml (p=0.001). All 5 factors remained significant in a Cox regression analysis that adjusted for baseline CD4 count.

CONCLUSIONS

High HBsAg loss rates occur in people living with HIV and HBV early after commencing ART. Our study suggests that TAF-containing ART regimens may be preferable as first line therapy in HIV-HBV co-infection.

摘要

背景

有效的乙肝治愈治疗策略仍是亟待满足的需求。我们旨在确定亚洲地区接受乙肝活性抗逆转录病毒治疗（ART）的艾滋病毒和乙肝病毒合并感染者（PLWH-HBV）中乙肝表面抗原（HBsAg）消失的发生率、动力学及预测因素。

方法

前瞻性招募了97例开始接受乙肝活性ART的PLWH-HBV患者，其中泰国94例，马来西亚3例，随后进行24个月的随访。计算乙肝血清学变化的时间。使用Mann-Whitney检验或卡方检验分析基线特征与HBsAg消失之间的单变量关联。采用Cox回归进行多变量分析。

结果

21例患者（22%）在随访期间HBsAg消失（每100人年11.7例），其中14例产生了抗-HBs。基线时乙肝e抗原（HBeAg）阳性的22/61例患者（36.1%）在研究期间HBeAg消失，其中15例产生了抗-HBe。大多数患者在第12个月的研究访视时HBsAg和HBeAg消失（分别为81%和63.6%），HBsAg和HBeAg消失的中位时间分别为5.8个月和12.0个月。单变量分析显示，与HBsAg消失相关的基线特征包括较高的丙氨酸氨基转移酶（ALT，p=0.005）、含替诺福韦艾拉酚胺（TAF）的ART方案（p=0.025）、较年轻的年龄（p=0.040）、较低的肝脏硬度（p=0.010）以及定量HBsAg<log102.0 IU/ml（p=0.001）。在对基线CD4细胞计数进行校正的Cox回归分析中，所有这5个因素仍然具有显著性。