Occult Hepatitis B Virus Infection and HBV Reactivation After Switching to Long Acting Therapy in Patients Living With HIV-1
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- Quantification of hepatitis B DNA (HBV-DNA)
研究概览
简要总结
The primary objective of the present project will be to investigate the risk of HBV reactivation (from virological reactivation to overt HBV infection) in HIV-1 carriers with occult HBV infection (OBI, is characterized by the absence of surface antigenemia, HBsAg negativity, with the presence of HBV-core antibody, HBcAb) and switching from antiretroviral therapy (ART) including nucleos(t)ides to long-acting formulation.
详细描述
Observational prospective, multicenter, single-arm study with additional procedure in people living with HIV-1 and having serological markers of previous HBV infection: anti-core antibodies and/or antibodies against surface antigen (HBsAb) and switching from nucleoside analogue therapy to long-acting therapy including cabotegravir (CAB, HIV-1 integrase inhibitor) + rilpivirine (RPV, non-nucleoside HIV-1 reverse transcriptase inhibitor) intramuscularly 1 time every 2 months.
Primary Objective To study the risk of HBV reactivation from the phase of possible virological reactivation (HBV-DNA >=10 IU/mL), when the liver enzymes are within normal limits to overt HBV infection. Overt HBV infection is characterized by positive HBV-DNA, possible positivity of surface antigen (HBsAg) with or without altered liver enzymes in HIV-1 patients with OBI, with switch from ART, which includes nucleos(t)ide analogues active on the two HIV/HBV viruses, to the long-term formulation in which nucleos(t)ide analogues active on the two viruses are not included.
Secondary Objectives
- To evaluate the effect, in the context of HBV reactivation, of HBV-RNA as a surrogate marker of the transcriptional activity of the covalently closed circular (cccDNA) which is present as an HBV replication intermediate at the hepatocyte level.
- Examine the mutational profile of HBV domains (pre-S1 and S genes, X gene), mutations in the nucleocapsid promoter region and the pre-core/core variant, capable of influencing HBV replication efficiency, including also the analysis of mutants characterized as viral escape.
Exploratory Objectives To study the mutational profile of the regions of the hepatitis B virus (HBV) able to influence replication efficiency.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years
- •Informed consent to participate in the study
- •HIV infection
- •Stable antiretroviral therapy (ART) in the six months prior to enrollment without virological failure defined by HIV-RNA>50 copies/mL in at least two consecutive determinations
- •Positive HBV anti-core antibodies (HBcAb) in the absence of hepatitis B surface antigen (HBsAg)
- •Absence of mutations associated with resistance to integrase inhibitors (INSTIs) and reverse transcriptase inhibitors (NNRTIs) by HIV genotypic resistance testing
- •CD4 Nadir >200 cells/mm3
排除标准
- •Any contraindications to the use of one or more long-acting drugs
- •Non-expression or withdrawal of informed consent to participate in the study
- •Pregnancy
- •Lack of HIV genotypic resistance testing
- •Virological failure (HIV-RNA >50 copies/mL in at least 2 consecutive determinations) in the 6 months prior to enrollment
- •Therapeutic interruptions in the six months prior to enrollment, excluding interruptions lasting less than a month due to tolerability
- •CD4 Nadir =<200 cells/mm3
- •Presence of biochemical signs of hepatocellular necrosis (AST, ALT > normal values as indicated in laboratory tests).
- •Cirrhosis and/or fibrosis score >F3 assessed by transient elastography (FibroScan).
结局指标
主要结局
Quantification of hepatitis B DNA (HBV-DNA)
时间窗: Baseline (start of long-acting therapy) weeks 12, 24 and 48
HBV-DNA increase respect to baseline viremia (=\>10 IU/mL) according to different time points (W12, W24, W48) after the start of LART.
次要结局
- Quantification of hepatitis B RNA (HBV-RNA)(Baseline and at weeks 12, 24 and 48)
- HBV mutational pattern by direct sequencing (Sanger)(Baseline and at weeks 12, 24 and 48)
研究者
Castagna Antonella
Prof
IRCCS San Raffaele